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~—
CONTENT MODULE 5.
pathophysiology of systemic circulation
and external respiration

Arrhythmias
Lesson 23. Heart failure.
can cause it?
23.1.] What is circulatory failure? What

which
Circulatory failure, or insufficiency of blood circulation, is a condition in
the organs and tiss of ueswith
the body
ne cardiovascular system cannot provide manifes tation of various
the necessary amount of blood. It is the most frequent
.
gisorders of the circulatory system failure; (2) insuf-
Insufficiency of blood circulation can be caused by: (1) heart
simultaneous failure
vessels; (3) cardiovascular insufficiency, i.e.
vess
bloodcy
of en
fici blood vessels.
of the heart and

What consequences for organs, tissues and the body as a whole has
circulatory failure?
groups.
Clinical consequences of circulatory failure can be divided into two
. They develop as a conse-
I. Violations of trophic supply of organs and tissues
lesson 27); (b)
quence of: (a) reduced delivery of oxygen — circulatory hypoxia (see
impaired supply of nutrients.
II: Disorders of removal of the end products of metabolism from the organs
and tissues. The consequence of this is the development of (a) non-respiratory
acidosis, (b) intoxicati

What is heart failure?

Heart failure is a pathological condition caused by the inability of the heart to
Provide blood supply to organs and tissues in accordance with their needs.
\ This is a condition in which the load on the heart exceeds its ability to perform
x tis manifested by the fact that the heart is not move all the blood
“at flows to it through the veins into the arterial channel.

How is heart failure classified?

I. Depending on the clinical course, a distinction is made between, (a

(b) chronic heart failure. LT
II. By the severity of clinical manifestations, heart failure may pe
eee ry rTETEatart-arnd-f-nhvions-(decompensated). 1) (@) higg,_
 301
How is heart failure classified?

I. Depending on the clinical course, a distinction is made between (a) acy

—Uey
(b) chronic heart failure. ) } ang
II. By the severity of clinical manifestations, heart failure may pe ( a .

(compensated) and (b) obvious (decompensated). ) Dig,

III. Depending on the predominant dysfunction of a particular part of the,
there are (a) left ventricular, (b) right ventricular and (c) total heart fajfyre ot
IV. According to the pathogenesis, there are: (a) heart failure fro, over
“Gee
(b) myocardial heart failure: (¢) extra-myocardial insufficiency. Ty |
NZ

Give a brief description of the various pathogenetic variants of heart

ailure.

I. The heart failure from overload develops as a result of the action of large
loads on a healthy heart by (a) resistance or (b) volume. In the first case, the re.
sistance to cardiac output is increased and in the second one, the blood flowto,
particular part of the heart is enhanced. This happens with heart defects, ype,
tension of the systemic or pulmonary blood circulation, arteriovenous fistulas o,
when very hard physical work is performed. In all these situations, the excessive
demands are made on the heart which has normal contractility.
Il. Myocardial heart failure develops as a result of primary myocardial dam-
age. It can be associated with (a) the destruction of the conduction system of the
heart (arrhythmic) and (b) the destruction of the fibers of the working myocardium
(myocardiopathy). Infections, intoxication, hypoxia, avitaminosis, disorders of the
coronary circulation, some hereditary metabolic defects are often the cause of its
development. In this case, the insufficiency develops even under normal or low
heart load.
————

Ill. Extra-myocardial heart failure develops as a result of the action of causes

i d to the myocardium. Its occurrence can be caused by a decrease
in the od to the heart (yeorolem) or by the obstacle
to diastole, asa
result of which the heart cannot accept al the blood flowing to it (accumulation of
exudate oror transu
éxudate transudate in the pericar avity, acute cardiac tamponade).
p

What types of heart overloads can cause the development of its failure?
There are two types of heart overloads.
1) Overload by volume (preload) occurs when an increased volume of boc
to the heart or to individual cavities. In these conditions, the heart or ts 2
flows
experiencing an overload should move the increased volume of incoming b!
into the arterial system. This is achieved by increasing the cardiac Butputin a2"
dance with increased venous return.
The heart experiences an overload with: ith a"
. %
a) an increase in the venous return of blood to the heart, in: particul
icular Vast
Wi
302

increase in the volume of circulating blood (hypervolemia) or an I1&==—

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tone of the venous vessels (a decrease in the acity of the venous

in the 295 of 522
sy stem); insufficiency of its valves. Thus, with aortic and mitral valve
rt defects — 1 ) : ilure of the
by hear
: 1 n overload
=of the left ventricle develops with a failure of ==
ciency
insufficief a
Cac craze and ¢riciieontid valua « an Aver 1~ad of the right ventri-
 a) an increase in the venous return of blood to the heart, in particula

302
increase in the volume of circulating blood (hypervolemia) or an incre
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capacity of the venous

in the tone of the venous vessels (a decrease in the
system): :
with aortic and mitral valve
b) heart defects — insufficiency of its valves. Thus,
ad
of the left ventri cle devel ops with a failure of the
insufficiency an overlo ventri-
ulmonary arter lv ricuspid valve — an overload of the right

occurs when the heart or some of its dr

cle. )
2) overload by resistance (afterload)resista nce which prevents th TT
fiorced tO work against increased maintain Jts
system. In this condition, the heart must
are @ bloodto the arterialoutput) 10 €Xp ulsion of
e (cardiaecc o despite the increased resista nce
miny
ut e volume (cardi
ood. s :
stance develop with
overload by resi d peripheral vascular resi
stance). With
re i n c r e a s e
d pressu ( is experienced by the
2) increased blooin the systemic circulation, resistance
rtension in the pulmona circulation it is
eft ventricle, and in case of hype
experienced by the right one; aortic
ings. Thus, with stenosis of the
b) heart defects ~sienesisof valve open valve
, with stenosis of the mitral
opening, left ventricular overload develops artery
stenosis of the pulmonary
opening left atrium overload occurs, with with steno-
es, ventricle overload,
opening the right ventricle overload evolv present.
sis of the tricuspid valveopening the right atrium overload is

tion for the heart when

What mechanisms can provide compensa
increaesed eloads —are acting on it?
n
an increase in the work of the heart
In the conditions of preload and afterload,
tory mechanisms.
is provided by two types of compensa
I. Urgent mechanisms of compensa tion of the heart. These include: a) heter-
anisms and d) inotropic effects
ometric, b) homeometric, C) chronoinotropic mech
of catecholamines.
myocardial hypertrophy.
II. Mechanisms of long-term adaptation of the heart —

What is the essence of the heterometric mechanism of heart

compensation?
compen-
The heterometric mechanism is one of the urgent mechanisms of
sation of the heart when it experiences the overlo ad Its essence is to
by volume.
increase the strength of the heartbe ats in the conditi ons of getting to the heart of
Increased blood volume.
i basis of the heterometric mechanism is the Frank-Starling law. It has two
a ations: for individual muscle fibers and for the whole heart. In the first vari-
bars ahgmae is expressed by the position: the greater the initial length of the
ore er (within certain limits), the greater the force of its contractions. For the
in eart, the following formulation is accepted: the greater the end-diastolic
2N2

L0lume of the ventricles of the heart, the greater their stroke volume.

|—-_
297 of 522

ond A. SM are.
 Rd fated a bat dd ett N-
Yolume of the ventricles of the heart, the greater their stroke volume. ly

|—_

The main manifestations of the

heterome tric compensation mechan;
(a) an increase in the end-diastolic pres
sure due to increased blood f om are
cavity of the ventricles and (b) an increase of the stro
ke volume, and Hid nto the
cardiac output by increasing the force of the
heartbeats. The tension fore, the
dial muscle fibers does not alter,
but only their length changes. That
mechanism is called heterometric is y
. "hy this
What is the homeometric mechanism of heart comp
ensation?
The homeometric mechanism is an urgent mechanis
m for the compen;
of the heart when it experiences the over
bylo
resisad
tance. Its essence is es
crease the strength of heartbeat in condi
tions of increasing resistance to the "
pulsion of blood.
Itis =
now shown that the
basis of this mechanism, as well as of the heter
ric one is the Frank-Starling law, i.e. an incre omet.
ase in the initial length of the fibers pr
the myocardium and an increase in the end-diasto
lic volume associated with it
The formation of a homeometric mechanism occur
s in such sequence. With
increasing resistance to the expulsion of blood,
the stroke volume decreases
sharply, as a result of which the end-systolic
volume of the ventricles incre ases,
As the flow of blood into the ventricles continues to be the
same, in the next cy-
cle of cardiac contractions the end-diastolic volume incre
ases. According to the
Frank-Starling law, this leads to an increase in the strength
of the heart contrac-
tions.
For a homeometric mechanism, the following changes in cardial
dynamics are
characteristic:
a) an increase in the end-systolic volume;
b) an increase in the end-diastolic volume due to a primary increase in the
previous index and not due to an increase in blood flow, as in the case of
a heterometric mechanism;
c) stroke volume, and consequently, the cardiac output, due to the increase in
the force of the heartbeats, remain at the same level despite the increased
resistance to the expulsion of blood.
With a homeometric mechanism, the tension of muscle fibers of the myocar-
dium increases, while their length does not change. Because of this, the name of
the compensation mechanism is homeometric.

What characterizes the chronoinotropic mechanism of heart

compensation?

The chronoinotropic mechanism (staircase phenomenon by Bowditch) is one

the urgent mechanisms of compensation of the heart for the action of incre2®s-
loads. Its essence lies in the fact that a rise of the heart rate (within oggln fr
increases
Uacade the strength of heart contractions. Simultaneously,dl the time of re'@”
Lc tri-
ation of the myocardium decreases which facilitates the rapid filling of the vent
304

cles of the heart with blood.

Currently, it is believed that the basis of the chronoinotropic mechanism is

ys EB
< of th€ ==
ationof the myocardium decreases which facilitates the rapid filling
[=
™ cles of the heart with blood.

Currently, it is believed that the basis of the chronoinotropic mechanism is

an increase in the inflow of calcium ions into the sarcoplasm of cardiomyocytes
during action potentials, the total duration of whi s with tachycardia.
An increase in the concentration of calcium ions in the sarcoplasm leads to an
increase in the amount of calcium-troponin complexes formed and, as a conse-
quence, to an increase in the contraction force of muscle fibers.
Chronoinotropic mechanisms are characterized by the following changes in
cardiodynamics:
a) the stroke volume increases (with preload) or remains constant (with after-
load). As aresult of an increase in the heart rate, the cardiac output increases;
b) the end-diastolic volume decreases if the inflow of blood to the heart is
constant or remains unchanged if the influx of blood increases;
c) the end-systolic volume decreases.

What is the role of catecholamines'in the mechanisms of urgent heart

compensation?

The involvement of catecholamines in the realization of urgent adaptation of

the heart to increased loads is associated with the ability of adrenaline and nor-
adrenaline to increase the force of the heartbeats - with a positive inotropic effect.
It has been established that under the influence of catecholamines, the num-
open the action
ber of Ca-channels of the sarcolemma, capable of being during
potential, increases. That is because catecholamines initiate a phosphorylation
of Ca-channels proteins through the cAMP-mediate mechanism. As a result of
these processes, the inflow of calcium ions into the sarcoplasm increases and
their concentration there increases, too. The result is a rise of the number of cal-
cium-troponin formed complexes with subsequent growth of the cardiomyocyte
contraction force.
The inotropic effect of catecholamines (and not the Frank-Starling law) is the
leading mechanism for adapting the heart to physical stress. In this case, the pa-
rameters of cardiodynamics change as follows:
a) the stroke volume increases;
b) the cardiac output is increased both by increasing the stroke volume and by
increasing the heart rate (positive chronotropic effect of catecholamines);
¢) the end-diastolic volume decreases (x-ray examination shows a decrease in
the volume of the heart);
d) the end-systolic volume decreases.

123.12 | What are the variants of long-term adaptation of the heart to the loads?
There are three variants of long-term adaptation of the heart.
on Hypertrophy of the heart in athletes (“adapted” heart). It develops with pe-
fiodic loads of increasing intensity, i.e. in conditions of training. It is a balanced
Aypertrophy, in which all the components of the heart are uniformly increased. Due wn
0 this hypertrophy, the functional reserves of the heart are significantly increased. m™

N
2. Compensatory hypertrophy of the heart (“over-adapted” heart). it is th
of pathological processes affecting the heart. There are two types of Compe 299 of 522
tory hypertrophy: ensa.
a) hvnertronhy due to overload (develops with heart deferte ko.
 tory ry hypertrophy:
2) hypertrophy due to overload (develops
-adapted” heart) isthe
2. Compensatory hypertrophy of the heart “ (“over-adap Iti

of pathological processes affecting the heart. There are two types of compen!
4
with heart defects, hype ens;
b) hypertrophy due to damage (typical of atherosclerotic lesions, myn)
opathy). SS10S, ~¥OCar;
Myo,
Development of compensatory hypertrophy of the heart is characterizeq by the
following features:
1) the pathogenic factor that causes hypertrophy is permanent:
2) compensatory hypertrophy, in contrast to cardiac hypertrophy in athlete
is unbalanced,
3) with compensatory hypertrophy, heart failure develops over time,
3. Atrophy of the myocardium (“de-adapted” heart). It is character
izeq bya ge
crease in heart weight as a result of prolonged hypokinesia and a decrease
i,

Piers wit duscosed ampicide

heart loading.

What mechanisms underlie the development of cardiac hypertrophy»

Prolonged increase in the load on the heart results in the
developmen
hyperfunction. The Tatter eventually causes structural changes in the heartt of js
- myo-
cardial hypertrophy.
The connection of hypérfunction with cardiac hypertrophy is mediated
by ac-
tivation of the genetic apparatus which comes as a
result of a change in the im-
portant indicator of energy supply of cells - the potential of
phosphorylation (PP):

_ ADP) xP]
SAE
where [ADP], [P], [ATP] are concentration in the
cytoplasm of cells, respectively,
ADP, inorganic phosphate and ATP.
The PP naturally increases in two cases:
a) with the increased use P which is always observed with increasing
functional load on cells (with their hyper
function);
b) with violation of the ATP formation which is typical for
various types of cell
dama ge.
An increase in the index of PP cause
s the appearance of substances - reg
lators\ of transcription in the ce
lls which, acting
thesis of messenger RNA on the matrix of geneson encodin
the genome, enhance the sy
g the structure of func-
tionally important proteins, including contractive protei
ns and enzymes. There IS
an opinion that the role of substances regulating transcriptio
n could be fulfilled bY
a number of metabolites, including cAMP, creati
ne, Mg?" ions, polyamines (spe”
mine, spermidine), and others.
.
Thus, the development of cardiac hypert
rophy can be described by such a ¢
quence of processes: an increase in the heart
load (hyperfunction) — increase”.
306

use of ATP that exceeds the intensity of its resynthesis

— an increase in the P”

> |
|a
\
1 PP TARDP UATP
tential of phosphorylation — the appearance or increase in the concentration of
300 of 522
~substances regulating transcription in the cells — an increase in the synthesis of
messenger RNA and processes of translation i
TT hi~ounthacie of etriictiiral
 CEE EM Typernraneaonty = 2———
™ use of ATP that exceeds the intensi of its resynthesis — an increase in the P”
ncreas In e °F

1 pp TARDP JATP
tential of phosphorylation — the appearance or increase in the concentration of
“substances regulating transcription in the cells — an increase in the synthesis of
messenger RNA and processes of translation in the ribosomes — enhancement
of biosynthesis of structural, functional proteins and enzymes — an increase in
myocardial wight, its hypertrophy.

ERIN What are the'stagesn the development of compensatory hypertrophy

of the heart?

According to the dynamics of metabolic, structural and functional changes

in the myocardium, there are three stages in the development of compensatory
cardiac hypertrophy.
1. Emergency stage. It develops immediately after the load increases. Where-
in, there Is a significant increase in the load per unit of muscle mass - the index
called the intensity of structures functioning (ISF) rises. Within a few weeks, the
weight of the heart increases rapidly due to enhanced protein synthesis
and thick-
eningof muscle fibers. -— A
2. Stage of completed hypertrophy and relatively stable hyperfunction. At this
stage, the process of hypertrophy is completed, the mass of the myocardumTo
longer increases, the ISF is normalized. The hypertrophied heart has adapted to
“the new loading conditions and compensates them for a long time.
3. Stage of gradual depletion and progressive cardiosclerosis. It is character-
ized by profound metabolic and structural changes that gradually accumulate in
energy-producing and contractile elements of myocardial cells. A part of the mus-
dies sand is repla
clefiber connective tissue, the ISF increases again. Pro-
by a ced
chronic
gressive depletion of compensatory reserves leads to the occurrofence
heart failure, and in the fUtGre = to circulatory failure.

What can be the cause of myocardial heart failure?

Myocardial heart failure develops as a result of primary myocardial damage.
Since the myocardium consists of two types of muscle fibers = (a) atypical ones
that make up the conduction system of the heart, and (b) contractile cells of the
working myocardium, the development of heart failure canassociated
be with
damage to both the first and the second ones. Hence, we can distinguish two vari-
of
myocardial
ants insufficiency of the heart:
a) caused by damage to the conduction system of the heart LTT
b) caused by damage to the working myocardium. Sometimes it is called-car—
womans
123.16 | What are cardiac arrhythmias? How are they classified?
Arrhythmias of the heart are called violations of rate, rhythm, coordination and
Consecution of its contractions. In cardiac arrhythmias, the heart beats with an
307

regular or abnormal rhythm.

The development of arrhythmias can be associated with violations of the 301 of 522
sic functions of the conduction system of the heart: om, eXcilabiiy :
ang
7 anndictivity Thicis a 0
 Arrhythmias of the heart are called violations of rate, rnythm, coordination and
Consecution of its contractions. In cardiac arrhythmias, the heart beats with an

307
regular or abnormal rhythm.

The development of arrhythmias can be associated with violations of the

sic functions of the conduction system of the heart: automatism, eXCitability =
conductivity. This is a base for the classification, according to which the follow q
four groups of arrhythmias are distinguished:
m;
Cu. Arrhythmias caused by disorders of automatis
II. Arrhythmias associated with impaired excitability;
II1. Arrhythmias caused by conduction disorders;
IV. Arrhythmias associated with combined disorders of excitability ang Coe
ductivity. =

What cardiac arrhythmias can occur as a result of a violation in the

automatism function?
—————

There are two groups of arrhythmias associated with disorders in the aytop,.
atism of the heart.
|. Nomotopic arrhythmias. Generation of impulses to contraction, as it normally
occurs in the sinoatrial node. This group includes:
a) sinus tachycardia — an increase in heart rate;
b) sinus bradycardia — a decrease in heart rate;
c) sinus (respiratory) arrhythmia — changes in the heart rate in different
phases of the respiratory cycle (the heart rate increases with inhalation
and slows down with exhalation). TT
II. Heterotopic arrhythmias are presented by sick sinus syndrome, also called
sinus dysfunction or sinoatrial node disease. Generation of impulses to contrac-
tion does not occur in the sinoatrial node, but in other structures of the conduction
system that are Somalis FE order. The syndrome develops as a re-
sult of a decrease in the activity or.cessation
of activity of the sinoatrial node in the
event of damage to its cells or primary functional disorders.

What are the causes and mechanisms of sinus tachycardia and

bradycardia?

Sinus tachycardia and bradycardia belong to the group of nomotopic arrhyth-

mias associated with violations of the automatism function.
The ability to automatically generate impulses depends on cells located in the
conduction system of the heart (p-cells), in which spontaneous slow depolarization
of the cell membrane occurs during diastole (Fig. 90). As a result, upon reaching
a certain critical level, an action potential arises. The frequency of impulse gener
ation depends on (a) the maximum diastolic potential of these cells, (b) the level
of that critical potential on the membrane, after which the action potential arises:
and (c) the rate of diastolic depolarization.
The change in the level of either of these parameters in either direction leads
to a change in the frequency of impulse generation or to the appearance of ote
of oe
sources of them. The latter is possible if these changes occur in other areas
308

heart capable of generating the action potentials. When (a) the maximal dias”

“N
302 of 522
I Critical
, mV

N
 padi Jike fanned Mad $C TTTTEETE TL Ir GUEOY TITOIGWWN LW WY BT Ses

sources of them. The latter is possible if these changes occur in other areas of the
stolic
& heart capable of generating the action potentials. When (a) the maximal dias

a
“¥

B Critical

Potential, mv
20+ potential

o
-40}

-80 Maximum diastolic ~ Slow diastolic

potential depolarization

1 1 1
0 1 2 3 Times

Fig. 90. Spontaneous generation of action potentials in cells of the sinoatrial node

potential of cells in the sinoatrial node decreases, or (b) the threshold critical po-
tential approaches it, or (c) the rate of slow diastolic depolarization increases, the
impulses are generated more often and eventually tachycardia develops. This is
observed under the influence of high body temperature stretching the area of the
sinoatrial node, the sympatheti iator. RE ——
Conversely, when (a) the maximal diastolic potential of cells in the sinoatrial
node increases (hyperpolarization), or (b) the threshold critical potential moves
away from it, or (c) the rate of slow diastolic depolarization decreases, the impuls-
es are generated slowly and bradycardia develops. This arrhythmia occurs when
the vagus nerve is stimulated.
Fluctuations
in the tone of the vagus nerve during the act of breathing can
cause (esplatory arrhythmia (the heart rate increases with inhalation and slows
down with exhalation). Respiratory arrhythmia is normal in children, but it can oc-
casionally occur in adults as well.

What arrhythmias occur as a result of impaired myocardial excitability?

What is the mechanism of their development?

The cause of arrhythmias associated with disturbances in the function of ex-

citability is the appearance of the so-called ectopic foci of excitation which gener-
ate extraordinary impulses to contractions.
In pathological conditions self-automatism of the underlying parts of the
conduction system of the heart (potential pacemakers) can manifest itself.
Such conditions may arise (a) if the automatism of the sinoatrial node decreas-
es or (b) the ability to generate impulses in other parts of the myocardium in-
Creases. In these cases, the frequencyof the impulses generated by the normal
pacemaker is not sufficient to suppress the automatism of other parts. It leads
tothe appearance of additional impulses from ectopically located foci of exci-
tation,
Among the arrhythmias of this group, thé most commonere ) extrasystoles ~~, &
and ( aroxysmal tachycardia. ©
Moan A —

|
p
303 of 522
PERIN What is extrasystolia? Name the types of extrasystoles and thei Main
electrocardiographic ci Erreteristioor ————
 4
x
PERT What is extrasystolia? Name the types of extrasystoles and the; Main
electrocardiographic characteristics.

Extrasystolia is a kind of arrhythmias caused by disturbances in the functig, n

excitability which is manifested by the appearance of premature Contraction o-
the heart or only ventricles. Such extraordinary heartbeats are call EXtrasystoe
Depending on the locaoftion the focus, from which an extraordinary impulse
emanates, several types of extrasystoles are distinguished: @) sinus, (b) atria) ©
atrioventricular and (d) ventricular (Fig. 91). Since the excitation wave that origing,
“ed in an unusual place spreads in an altered direction, this is reflected on the gg,
acl type of extrasystole has its own Slectroc ardiographic
trocardiogram. Each p; -
ectopic ocus
which allows to determine the place of the —_— of e citation.

’ T
A !

Fig. 91. Extrasystoles: a - atrial; b — ventricular

Sinus extrasystole occurs due to premature excitation of a part of the cells in

the sinoatrial node. Electrocardiographically, it does not differ from
normal con-
traction, except for shortening the diastolic interval of T-P. Due to the shorteni
of the diastole and the decrease in the filling of the ventricles, the
pulse mat
xt rasystole is reduced.
The atrial extrasystole is observed in the presence of
tation in various parts of the atria. It is characterized (a) by foci
ectopic
of exci
a
the distortion of the
shape of P wave (reduced, biphasic, ne ative) with
the QRS complex preserved
and (b) by some extension of the diastolic interval after
the extrasystole.
The atrioventricular extrasystole is observed with an appear
ance of an addr
tional impulse in the atrioventricular node. A wave of
excitation originating from
the upper and middle parts of the node spreads
in two directions: in the ventricles
normally and in the SE rdrade. In this case, the negative (wave P
can be su
erimposed on the QRS complex. The diastolic inter
somewhat elong
val after the extrasystole i
ated.
The ventricular extrasystole is characterized by
the presence of a full compe™
satory pause after a premature contraction. It arises from the fact that
citatio n that covers
the
x.
ake Lill \ the ventricles is not transmitted through the atrioventricu
node to the atrium, and another normal excitation impulse
coming
i
ventricles being in the refractory from
noatrial node does not extend to the
N >
phase:
n
the $*
next contraction of the ventricles occurs only after the arrival of another no™
—_—
——F. WE alive Oar —
impulse to them. Therefore, the duration of the compensato
A 310

ry pause, together ¥"

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receding interval, is equal to the duration of two normal diastolic pauses. Since
the p:
he excitation wave with ventricular extrasystole spreads through the ventricles
304 of 522
bh in the forward and retrograde directions, this is accompanied by a significant
distortion of the QRS complex sha
 — VMAs TAtEIid i ne ventricles being in the refractory phase. [Lied
next contraction of the ventricles occurs
pause, together“2 W!_L
ther norm?
arrival of another
the anival
iimpulse onlythe after
p to them. Therefore, the durationws ofonly after the
compensatory

=
Tand op" t Fukl
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the preceding interval, is equal to the duration of two normal diastolic pauses. Since
the excitation wave with ventricular extrasystole spreads through the ventricles
poth in the forward and retrograde directions, this is accompanied by a significant
distortion of the QRS complex shape.

[23.21] What is paroxysmal tachycardia? How is it characterized?

paroxysmal tachycardia is an arrhythmia caused by disturbances in the excit-

ability function. It is manifested by the appearance of a group of rapidly repeating
extrasystoles that completely suppri iological rhythm.
| tachycardia, the normal rhythm of the heart is suddenly inter-
— .
With paroxysiI
rupted
up” by 2 gf contraction
ag(attack ; s from 140 to 250 beats per minute. The dura-wll
several minutes, after
tion of the attack can be different — from a few seconds to
“which it also suddenly stops and a normal rhythm is restored.
The foch of pathological excitation can be located in atrium atrioventricular
node and ventricles. Hence, there are the following kinds of paroxysmal tachycar-
“dia: (a) atrial,
atriov (b) entricular and (c) ventricular. The first two are combined
into a group of supraventricular disorders.

CEWZA What arrhythmias occur as a result of impaired myocardial conductivity?

There are two groups of arrhythmias associated with conduction disorders.
I. ear block. These are arrhythmias caused by a slowing down or complete
cessation of the impulses in. conduction system of the heart. x
a
The cause of blockade is most often the damage to the conduction pathways
due to various factors: (a) ischemia, (b) inflammation of the myocardium (myo-
carditis), (c) compression of the fibers in the conduction system by scar tissue or
calcified deposits and others.
and the atria,
Conductivity disorders can occur between the sinoatrial node
inside the atria, between the atria and ventricles and in one of the branches in
the bundle of His. Therefore, the following types of block are distinguished: a) in-_
traatrial, b) atrioventricular, ¢) intraventricular.
II. Accelerated conduction of impulses - Wolff-Parkinson-White syndrome (see
question 23.24). WP - sym
block of the heart.
PEPE What is a characteristic of the atrioventricular
~~
of the
Depending on the severity of conduction disorders and the features
electrocardiographic picture, three degrees of the atrioventricular block are distin-
guished (Fig. 92).
in the time of the impulse
(Block of he 1st degree is manifested by an increase
conduction from the atrium to the ventricles which is accompanied by an exten-
Sion of the P-Q interval (above 0.2's).
ock of the 2nd degree is characterized by the fact that not all impulses pass
311

Into
venthetricles

305 of 522
 HVLR OT Ine
eT 2nd degree
Se
1S Lhdlduitiietl By Bis Ter a eee L od
into m™
S.

iiE
H
HAE
Fig. 92. Atrioventricular block: a - 1% degree; b — 2 degree (Mobitz I);
¢ ~ 2 degree (Mobitz Il); d - 3 degree (complete transverse block)

There are two types of electrocardiographic changes that can occur with block
of the 2™ degree.
Type | (Mobitz )is characterized by a progressive increase in the P-Q interval,
until one of the excitations, most often the eighth-ninth, is not carried to
the ven
tricles and falls out. After this fall, the interval P-Q is restored, gradually lengthen
ingwith each subsequent contracion of the heart (the periods of Wenckebach, of
Mobitz). It is believed that this phenomenon is associated
with the progressive
difficulty of conducting impulses through the atrioventricular node.
Type
(Mob Il itzIl). The loss aL ORs complexes and ventricular contraction®
occurs without
pro a gressi
extension ve
of the P-Q interval. Every
second
or third
contr
can actio
fall out, or conversely,
n only every second, third
fourtor atrial
hexc"
tation is conducted. This type often precedes complete block.
312

\
306 of 522

3rd
glock of the degree, or complete Lansverse block, It develops when no
~~ frm the atria can no ntririace ce tore
 vos x ER, OF Bonversely, only every second, third or fourth atrial €2
© tation is conducted. This type often precedes complete block.
™m

— \
3rd
glock of the degree, or complete transverse block. It develops when no
impulse from the atria can pass into the ventricles. In this case, the centers of
automatism, which are below the
atrioventric node (the pacemakersof the
ular
(Tq OTE) re activated. The frequency of their generated impulses is much
ower (from 20 to 40/min) which causes a low frequency of contractions of
the ventricles (idioventricular rhythm). Thus, with complete transverse block
the atria and ventricles contract independently of each other, each section in
its rhythm: the atria with a frequency of about 20-40 contrac-
70, ventric— les
tions/min. Two independent rhythms are registeredon the electrocardiogram:
atrial (P waves) and ventr(QRS r They are not
complexes).
icula in
connected
anyway. a
“Especially important is the time of the transition of an incomplete block to a
complete one, when no im ia come to the ventricles. Slow dia- p
stolic depolarization in potential pacemakers occurs only some time after the ces-
sation of impulses arrival from the sinoatrial node. This period is called a pre-au-
tomatic pause, during which the asystolia of the ventricles is observed. Due to the
cessation of blood flow to the brain, there is a loss of consciousness, convulsions
(Morgagni - Adams - Stokes syndrome). Death is possible, but usually with the
resumption of the ventricle contractions, these phenomena pass. The syndrome
can be repeated many times.

What can be the cause of the Wolff-Parkinson-White syndrome?

Wolff-Parkinson-White syndrome is characterized by an accelerated delivery
of impulses from the atria to the ventricles which leads to premature excitation of
the latter. As a result, tachycardia develops, and the P-Q interval on the electrocar-
diogram decreases.
The reason for the development of this syndrome is the existence of additional
pathwaysof carrying out impulses. Such paths include:
a) the Paladino-Kent bundle is a modified myocardial tissue localized in the
zone
atrioventricular
of the ring. There may be two bun ft and right)
located respectively in the mitral and tricuspid rings. These bundles con-
duct impulses from the atria to the ventricles bypassing the atrioventric-
ular node;
b) fhe Mahaim bundle. It connects the upper part of the bundle of His with
the ventricles;
¢) the James bundle. It connects the atrium with the lower part of the atrio-
ventricular node or the bundle of His.
With additional conducting paths, impulses are carried out faster and reach
hefore the impulses that go in the usual way through the atrioven-
the ventricles
Yicular node. This leads to premature activation of part of the ventricles, anoth-
vor them is excited later by impulses passing through the atrioventricular
Node, EEE
313

Ba |

aaus
disturb
(Tre easassswisabaimulian
BETTE What arrh sssm ance
 31
ny
Tq
i occur as a result of simu
; , ce
imultaneous disturban
EEEER What arrhythmias
of excitability and conductivity functions? What are the mechanisms of their
development?

1. Atrial flutter (the frequency of atrial contractions is 250-400 per minute).

400-0
2 Atrial fibrillation (the frequency of impulses occurring in the atria is

can crogs ;
fibrillatio have the same causes and can cross intg
erryflutter and atrialial fibrillation
Per Atrial
each other. } Co
3. Ventricular flutter (the frequency of ventricular contractions is 150-3gg per
minute). }
4. Ventricular fibrillation (the frequency of impulses in the ventricles is 300-50,
per 1 min, the heart does not contract, does not perform the function of the pump)
The basis of this group of arrhythmias is the formation of closed circles through
which the excitement circulates in the heart giving it a stable, autonomous, inge-
pendent of the pacemaker, character. Such a mechanism of arrhythmias is calleg
the “repeated impulse entering“or “re-entry” mechanism (Fig. 93).
at a
certai
Under normal conditions, the excitation that has arisen point of the
n
heart does not return because it attenuates coming here in the absolute refractory
period.
There why impulses returning to the point of primary exci-
tation do not die out but cause new ones that circulate around in a circle without
fading for a very long time supporting themselves.
1. An increase in the path through which impulses circulate. In this case, the
impulses return to the point of origin of the primary excitation already when the
cells of this area have come out of the absolute refractory period and are able to
conduct impulses further. This mechanism of arrhythmia formation is typical for
all heart lesions which are accompanied by the expansion of its chambers.
2. Decrease in the speed of impulses conduction, even if the normal path length
for the excitation going in a circle is maintained. Since the time during which the
impulse returns to the starting point increases, the action potentials that have
come here no longer catch the muscle fibers in the refractory state. The slow-
ing down ofim ulses can cause this type of arrhythmia in the following cases:
a) block of Purkinje fibers, (b) ischemia of cardiomyocytes, and (c) hyperkalemia.

Purkinje
fibers

ZN
Norm | Damage
Cardiomyocytes
: | Fig. 93. Mechanisms of impulses recirculation (re-entry
mechanism)

308 of 522
shortening of the refractory period of muscle fibers. If the time during which
circle
oe otory.period lasts is sheilenodmuenithhonommallongibobihe
 = N s ANN
|fsigh Norm
t ! Damage
Hi Cardiomyocytes

314
|
of i
Fig. 93. i Mechani SMS y mechanism)
f s of impulses recirculation (re-entr

= rs rn eriod of muscle fibers. time

If the len during which
3. Shortenin the no rm a gth of the cicle
sts is shortened, even ven with the normal length of the circl
wit h
”
he refractory per
imp uls es the exc ita tio n can come to the ) startiyngstari o poinne iy
and the speed of the recovered thei
cells of thisf area have
moment when the h repeated electrical stim-A
ion pot: entials. This situation arises wits,
ther con duct act ti on of ce rt ai n medicati on in particular rr
ation of the heart, wi th the ac atria and
of excitation can occur both in the
Formation of pathological circles are called flutter
orders that appear in this case oo
in the ventricles. Heart rhythm dis
and fibrinaliol:
llation?
23.26 What are the signs of atrial fibri
excitation occurs in the walls of
Atrial fibrillation occurs when the circulation of (Fig. 94). —
by flutter of fibrillation
the atria. It can be manifested

and fibrillation (b)

Fig. 94. Atrium flutter (a)
aches250-1>
atri a, the fre que ncy of their contractions re
With the flutter of the ina bil i of the icles to reprod
e
e, due to the d
nel minute. In this cas develops; the ventri
the atr ia, a relative cardiac block traction since the re-
, third, or fourth atrial con
igh rhy thm of
ry se co nd may
with a contraction to eve the ref rac tor y peri od. Ventricular contraction ry
ent er
maining excitation waves This causes severe cir
culato
occu r sooner than their sufficie nt fillfling with blood.
disorders. fibril-
atria reaches 400-60 0 per minute, atrial
If the number of impulses in thevidual muscle fibers are contracted, and the en-
lation occurs. In this case Qn indi its participation in the
pumping
let e CO NT E
ract io n,
tireatrium is in a state of incomp
ete cont h individual
ly arr ivi ng at the atr ioventricular node throug g its ex:
of lod géases- Random the impulses are mostly
incapable of causin 2
fi be rs of at
the ri um , state or donot reach
muscle
Citati . the no de in the refractory ©
e is stimulated irregularly
find
ra That is because they atr iov ent ric ula r “od
the
© threshold level. Therefore,

—~ mm
=
 m= = =~ = .
t the atrioVentieaner
causing its ex-
mostly incapable of
muscle fibers of the atrium, the impu |ses are te or do not reach
de in the refractory sta

315
: ventricular node is stimulated irregularly
- © Sion. old islevel.
threshThat se fore,
becauThere atrioventricular
they fiec”
the

and ventricular contractions are of an accidental nature. As a rule, the Number

ventricular contractions per 1 minute exceeds the normal value. Often, Ventricy,
contractions occur before they are filled with blood and are not accompanieq,
pulse wave. Hence, the pulse rate is less than the heart rate (pulse deficit).
Most often, the cause of atrial
“Most. illation
i fibrillation :
nosi of the left atrioven
iis (a) stenosis
ular orifice, (b) hyperthyroidism, (c) atherosclerotic cardiosclerosis.

What is flutter and fibrillation of the ventricles? When do they occur ang
how do they manifest themselves?

This kind of arrhythmias is the most dangerous among all the rhythm gigy,,.
bances: if the heart is not withdra uch a state within 1-3 minutes, almost
always death occurs.
The occurs when the impulses come from one ectopic f,.
cus of excitation localized in the wall of the ventricle. This focus generates req.
lar, repeated pulses with a frequency of 150-300/min. In such conditions a large
pathological circle for circulating excitation arises, which, by the mechanism of
“re-entry”, supports itself. On the ECG, there are smooth waves with relatively reg-
ular and identical in amplitude oscillations. —
Ventricular fibrillation is due to the impulses that occur very quickly and ieg-
ularly in a large number of ectopic foci of excitation in the ventricles. This causes
chaotic, uncoordinated contractions of individual muscle fibers and makes it im-
possible to synchronously contract the heart muscle as a whole. A low-voltage ~
i
wavy line with different amplitude and spacing between individual oscillations is
recorded on the ECG.
During ventricular fibrillation, some parts of the myocardium contract, while
others relax. In such conditions, the propulsive force of the heart contractions is
practically lost, the pumping function of the heart ceases the circulation stops, the
consciousness is quickly lost (after 4-5 seconds) and eventually death occurs.
The causes of ventricular fibrillation are different:
a) the passage of electric current through the heart;
b) acute failure of the coronary circulation causing myocardial ischemia and
its infarction; -
c) anesthesia with chloroform, etc.
During ventricular fibrillation, it is necessary to immediately defibrillate = 10
pass through the heart a short, strong, single electrical discharge. As a result,
al _
of the myocardial fibers are depolarized and asynchronous excitation of muscle
flberq ceases. temporary asystole (3-5 s) occurs, followed by restoration of the
contractions of the heart in the rhythm that the sinoatrial node defines.

What may cause the violations of the contractile function of myocardium”

Five processes which determine the contractile function of the heart occur "
the cells of the working myocardium. All of them can be broken and form the bas*
316

for the development of heart failure. ERE

— 310 of 522

inrdoare Of MVOCArdia TTT rT TTT ye ————

 Elan Vial THdy Laust HIE ViDiations of the contractile function OF My©Guaizi=
ur in
Five processes which determine the contractile function of the heart occ
© the cells of the working myocardium. All of them can be broken and form t he basi$
om forthe development of heart failure.

—
to impairment of:
pisorders of myocardial contractility may be due ’
1. Excitation of cardiomyocytes.
2. Electromechanical coupling.
3. The actual contraction processes.
4. Relaxation processes.
5. Energy supply of the myocardium.

| What factors affect the character of the action potential and the
excitability of cardiomyocytes? What electrophysiological signs are the
manifestations of their impaired excitability?

The main characteristics of the action potential (continuity, amplitude, steep-

ness of depolarization) and excitability of cardiomyocytes) depend on the follow-
ing factors (Fig. 95):
Action potential, mV

Fig. 95. Action potential of the myocardial contractile cells:

zation
| - phase of the quick depolarization, Il - phase of the slow repolari
(phase “plateau ’); Ill — the phase of rapid repolari zation

comes up to the cardio-

a) the character of the electrical impulsation which
heart. In arrhythmias, it
myocytes through the conduction system of the the
is possible to disrupt the main parameters of the action potentials of
myocardial fibers and its excitability;
ma of cardiomyocytes, and
bythe condition and properties of the sarcolem
ical agents known to be capa-
especially the ion channels. There are chem
of these channels. These are
ble of selectively disrupting the conductivity
lo channels, Ca-channels, K-channels;
ved in the formation of electrical
¢) concentrations of extracellular ions invol
. In vivo, the extracellular con-
potentials on the cardiomyocyte membrane
SE

centration of potassium ions is the most important.

of
Changes in the excitability the myocardial fibers can be manifested by:
tials, and consequently, in the
1. Changes in the duration of the action poten potentials
Stre ng
of the tbeats. The decreainsethe duration of actionextra
hearth cellular
occurs when (a) the frequency of stimulati on increases, (b) the extracellu
of acetylcho-
oncentration of § potassium ions enhances (c) with the action for
i
yi in the duration i
of the action ials
potentials isi charac teristic
317

. he,
ig
 ad Di autls Loesbaddbade yc hmmde— adi
Aenrease in the jon of action p potentials
strength of the heartbeats. The decrease in the duration
— increases, (b) the extracellu lar
occurs when (a) the frequency of stimulation
ee

Ssiu
tass m ions
ium a n of acetetyylcho-
he actio
ions enhances (c) with the
conc i characteristic for
ntials is
res; duration of the action pote

317
ne Ths nc ni

2. Changes in the duration of absolute

rT PT pe andVRrelative
TET refractory
IE periods, ang con.
sequently, the ability to accept impulsation (to adopt the rhythm). The dura;
; on of
these periods depends on the duration of the action potentials.
VY VAS

What factors affect the characteristic of electromechanical coupling jy

the myocardium?
1) the duration of the action potential;
2) the frequency of action potentials;
3) concentration of calcium ions in the extracellular fluid;
4) the condition of Ca-channels of cardiomyocyte sarcolemma;
5) the state of systems for the removal of calcium ions from the cytoplasm of
muscle fibers.

How do changes in the duration and frequency of action potentials

affect the streng of the heartbeat?
th
Changes in the duration of action potentials in cardiomyocytes occur due to
the shortening or lengthening of the “plateau” phase, during which the Ca* ions
enter through the potential-dependent Ca-channels of the sarcolemma into the
sarcoplasm.
Taking into account the fact that the concentration of Ca?" ions in the Cyto-
plasm of muscle fibers determines the num in complex-
es, and consequently, the force of contractions, the following conclusion can
be
drawn. With a decrease in the duration of the action potential, the entry of Ca*
ions in the sarcoplasm is reduced and, as a consequence, the force of contraction
of the muscle fiber decreases. With an increase in the duration of the
action po-
tential, the opposite is true.
The duration of the action potential of cardiomyocytes decreases with
hyper-
kalemia and when acting on muscle fibers of acetylcholine. The
increase in the
duration of the action potential is characteristi c of hypokalemia and
cooling of the
heart.
As the frequency of action potentials increases, in spite of the fact that the
duration of each individual otential, and conse
quently of the “plateau” phase,
decreases, the total duration of this phase per unit time increa
ses. This means
that in the cardiomyocytes higher concentrations of Ca?"
are created and, as @
consequence, the force of contraction of muscle fibers increases. This, in partic
ular, explains the chronoinotropic mechanism of urgent heart compensation (se¢
question 23.10).
When
\ the ffrequency of action potentials decreases (for example, with
brady:
cardia), the total duration of the “plateau” phase per unit time decreases wh
leads to a decrease in Ca? concentration in the sarcoplasm and a decrease in 1"
force of the heart contractions.
318

ES JEy | Ey I I Ps a = —-
 So
inm inim - the sarcoplasm
Ca?* concentration
in concentrat Sm— o
leads toa decrease in Ca” and a decrease In the
force of the heart contractions. =

318 How does the extracellular concentration of calcium ions affect the
force of the heart contractions? What is the “calcium paradox"?

In the early twentieth century Ringer showed that the isolated heart quickly
stops in a solution devoid of calcium ions. At present, it is known that the cause
of this is the complete uncoupling of excitation and contraction. Under normal con-
ions entering during the “plateau” phase of the action potential
ditions, calcium
from the extracellular medium into the sarcoplasm of cardiomyocytes “trigger” the
release Of Cet ogo eliculum and replenish its stores in these
muscle fiber structures. With a decrease in the extracellular concentration of Ca?"
its reserves in the sarcoplasmic reticulum are rapidly depleted, the concentration
of Ca? in the sarcoplasm decreases and, consequently, the force of the heart con-
tractions decreases.
“Calcium paradox” is an experimental phenomenon that develops after calcium
ions are added to a calcium-free solution with which the heart has been perfused
for a few minutes. In this case, irreversible damage to the myocardium develops:
the level of ATP and phosphocreatine decreases, proteins come out of the cardio-
myocytes including myoglobin and enzymes (creatine kinase), the sarcoplasmic
reticulum is destroyed.
“Calcium paradox” is explained by the fact that there is a dissection of the
of the cardiomyocytes (the outer layer of the glycocalyx detaches from
glycocalyx
the inner one) in the calcium-free solution. As a result, the permeability of the sar-
colemma to calcium ions increases significantly. When Ca? ions are subsequently
introduced into the medium, their massive entry into the cells takes ra =
concentration of these ions in the sarcoplasm sharply increases, whic
the calcium damage mechanisms (see lesson 7).

FREE] What factors influence the condition of the calcium channels in the
sarcolemma of cardiomyocytes? What can cause their activation and blockade?

In the sarcolemma of cardiomyocytes there are potential-dependent slow

_Ca-channels. These are protein molecules inserted in a plasma membrane capa-
ble of passing calcium ions through themselves when they are open. Opening of
Ca-channels i Not all
when the membrane is depolarized. channels can be
Opened, b it only't ose that are phosphorylated (activated).
Phosphorylation of Ca-channels results in an increase in the number of chan-
nels that can open when the action potential arises. Because the reaction of phos-
phorylation is due to an increase in the concentration of CAMP in the sarcoplasm
of muscle fibers, all factors that cause cAMP formation lead to the activation of
Ca-channels, Such factors include, in particular:
3) adlioiamings and pharmacological agents that activate B-adrenergic re-
eptors;
b) inhibitors of phosphodiesterase (methylxanthines: theophylline, Caffeine, )
etc).
319

—
Vv
 These agents increase
the cAMP content either by activating adenylate cy,
(acting on B-adrendreceptors) or by inhib truction MP (phaser
rE Spho-
With theinhibitors).g
diesterase nnels, a positive inotropic effect of Catechg).
~
amines is associated. It is realized as follows: catecholamines — activation
B-adrenergic receptors — activation of adenylate cyclase — formation of cAMP _,
activation of protein kinases — phosphorylation of Ca-channels of sarcolemma _,
increase in the entry of Ca* into sarcoplasm during action of potential —, rig, of
Ca? concentration in sarcoplasm — increase in cardiac contraction force,
In the conditions of blockade of Ca-channels, the entry
of Ca® ions into the 5,
coplasm of cardiomyocytes decreases and, consequently, the force of the heart
contractions diminishes.
The blockade of the Ca-channels is caused by:
a) endogenous factors — deficiency of ATP, cAMP deficiency, hydrogen ions
(acidosis);
b) exogenous factors — divalent ions (Ni?*, Co*, Mn*"), some trivalent ions
(La*), organic compounds used in practical medicine (verapamil, nifed io
ine, etc.).

What factors influence the state of systems for removing calcium ions
from cardiomyocytes and, consequently, the strength of the heartbeats?

Such factors include:

a) cardiac glycosides. They are pharmacological preparations of plant ori-
gin, which increase the strength of cardiac contractions (digitalis prepara-
tions, strophanthin, etc.);
b) endogenous digitalis-like and strophanthin-like factors. It is believed that
cardiac glycosides, long used in medicine, mimic the action of endoge-
nous natural factors. The physiological significance of the latter is not fi-
nally established.
The mechanism of action of cardiac glycosides and similar endogenous factors
is associated with inhibition of the activity of Na-K -ATPase of cardiomyocytes. A
consequence of this is a disruption of the Na-K-pump work on the sarcolemma,
a decrease in the concentration gradient of Na* ions on both sides of the plasma
membrane of the muscle fibers. This leads to disruption of the Na-Ca-exchange_
mechanism in cardiomyocytes, as a result of which the removal of Ca?* from the sar-
coplasm in the extracellular environment decreases and the intracellular Ca* com
centration rises. The latter also causes an increasein the strength of the heartbeats.

What determines the strength of contractions of individual

cardiomyocytes?

The force
contractions
of of the muscle fibers of the heart is affected by: A
1) the concentration of Ca? ions in the sarcoplasm. The dependence is the fo
320

lowing: the higher the content of Ca?" in the sarcoplasm, the more Ca™* complex -

ot
— |
med with the troponin C, the more the binding centers (active centers) on
ue ic myofilaments are released, the more “bridges” between the actin and the 314 of 522
a heads are formed, the greater the farce of muscle fiber contraction. When
myos™ ation of Ca?* in the sarcoplasm decreases, everything occurs the oth-
 eo with the troponin C. the more the binding centers (active centers) on
2 inic myofilaments are released, the more “bridges” between the actin and the
the force of muscle fiber contraction. When
& osin heads aré formed, the greater
il concentration
:
of Ca” in the sarcoplasm decreases, everything occurs~ the oth-
of way around -
2) the degree of affinity of troponin C to calcium ions. Hydrogen ions and inor-
anic phosphate. binding to troponin C, make it impossible to interact with Ca?*
ingina reduction in cardiomyocyte :
contraction;
result 9 -
3) the state of the contracti le proteins - actin and myosin. The mutual arrange-
ment of actin and myosin myofilaments is of great importance. It underlies the
dence determined by the Frank-Starling law. With a very strong stretching of
the m uscle t amountr of formed actomyosin “bridges” decreases - this
fibers, the
Jaw does not “work”, th ¢force pf the contractions of the hea
4) the P, the hydrolysis energy of which ensures the sliding
other.
of the muscle filaments relative to each

What underlies the relaxation of cardiomyocytes? What mechanisms

de the removal of calcium ions from the sarcoplasm of myocardial fibers?
muscle?
What can be the cause of impaired relaxation of the heart
the re-
The main process that determines the relaxation of cardiomyocytes is
sarcoplasm, and, as a result, the Ca* concentra-
moval of calciu m ions from the
In this case, the complexes of
tion in it decrea ses and becomes below 10” mol/l.
sin shifts wit res pect to the actin filaments
h
Ca? with troponin C decay, tropomyo
ction stops.
and closes their active centers — the contra
There are three mechan is ms for re mo vi ng Ca** ions from the sarcoplasma of
cardiomyocytes:
lum. Ca* is re-
1. Ca-pumps of the plasma membrane and sarcoplasmic reticu
sarco plasmic reticulum cisterns,
moved into the extracellular environment and the ATP energy to
of them which uses
respectively. Ca-ATPase is a constituent part
carry out the active transport of Ca** ions.
in the extracellular envi-
2. Na-Ca exchange mechanism. It removes Ca? ions of
It uses the energy
ronment. It is a kind of secondary active transport (antiport).
of the plasma membrane, sO
the sodium ion concentration gradient on both sides
ing this gradient.
it depends on the work of the Na-K pump creat with a signifi-
3. Ca-accumulating function of mitochondria. Itis activate only d
plasm , which often happens in
increasein the content of Ca* ions in the sarco
cant plasm into the matrix
conditions of pathology. The removal of Ca™ from the sarco
occurs due to the energy
mitachondiia
ofthe liberated during the transport of elec-
active transport
n. The use of this energy on the
tons through the respiratory chai rnative way to oxid ativ e phos phorylation.
fCa® ions in the mitochondria is an alte
diomyocytes are:
The main causes of impaired relaxation of car
and Na-K
ci of
en ATP.
cy In this case , the energy supply of the Ca-
I de fi omyosin “bridges”
ps is disrupted, and also the splitting of the act
Pum
321

es
formed during the contraction donot occut.

-
~~
h
b) disruption of the work of Ca-transporting systems. There are know,deve
to the 315 of 522
itary defects of proteins of the Ca-pumps that are leading Op-
ment of cardiopathy.
ge a da atinm arn anifoctedhv the Aavata —
 TUTIN ITE RIE HTtVVIiviE IIe Te MT ————

The main
J impai ed relaxat
¢. auses of impair ation ion of cardiomyocytes are:
and s
Ca-due Na-K
3) d~clenc of ATP.
deficien ycy of case, the ener gy supply of the osin
this case,
TP. : InIn this “bridges”
&
AIF

Pumps is disrupted, and also the splitting of the actom

formed during the contraction does
not occu.

-
~~
b) disruption of the work of Ca-transporting systems. There are known he,
itary defects of proteins of the Ca-pumps that are leading to the deve
ment of cardiopathy.
Disorders of cardiomyocyte relaxation are manifested by the developmen; of
muscl
—_ —actures.
e contr

What is the significance of ATP in the function of myocardial cells?

What can be caused by violations of energy metabolism in the heart muscle?
for:
The energy of ATP in functioning cardiomyocytes is used
1. Mechanical work of myofibrils contractions (sliding of myofilaments relatiye
to each other).
2. Osmotic work — active transport of Ca?, Na, K* ions against concentration
gradients (work of ion pumps).
3. Phosphorylation of proteins that make up Ca-channels and Ca-pumps of sar.
coplasmic reticulum.
Disorders of energy supply of the cardiomyocytes can be associated with vio-
lations of: or
a) resynthesis of ATP (hypoxia, starvation, vitamin deficiency, decreased ac-
tivity of energy metabolism enzymes); oT
ria
b) transport of ATP from the mitochond to the sites of its use (violations of
the creatine kinase transport system);
c) utilization of ATP (decrease in the ATPase activity of cardiomyocyte struc-
tures).

PERTA What are the differences between hypocalcic and hypercalcic variants
of heart failure?

The modern level of knowledge about the molecular mechanisms of the con-
tractile function of the heart allows to distinguish two fundamentally different
pathogenetic variants of heart failure: (a) hypocalcic and (b) hypercalcic which are
characterized by a corresponding decrease and increase in the concentration of
Ca? ions in the sarcoplasm of cardiomyocytes.
n
The hypocalcic variant develops as a result of disturbances in stimulatioand
electromechanical coupling in fibers of the myocardium. It happens with (a)ar
rhythmias (bradycardia of various nature, blockade), (b) short-term myocardial isch
emia (phosphorylation of Ca-channels is impaired as a result of ATP deficiency).
(c) acidosis (blockade of Ca-channels by hydrogen ions), (d) hypocalcemia. These
processes are manifested by decrease in the strength of heartbeats. The main priv
of
ciple of the treatment is an increase in the content of Ca** ions in the sarcoplasm
lycosides:
cardiomyocytes during the systole of the heart. To do this, (a) cardiac
(b) catecholamines = B-adrenomimetics, (c) paired electrical stimuli are used:
The hypercalcic variant develops (a) as a result of increased entry of ca” or?
§ into the sarcoplasm of cardiomyocytes from the extracellular medium Gh
® of damage to the sarcolemma, in which its permeability increases) of (b) due

— — Ee ee ~ — ir -—
 | -

pm A

jolations of removal of Ca” from sarcoplasm (ATP deficiency, impaired function

of Catransporting Systems) It manifests itself in the development of contracture
rerconracton) of yetbrls as a result of which relaxation of themusclefi-
bers, an consequently, their subsequent contraction becomes impossible. The
main principle of treatment is a decrease-in the content of Ca? ions in the sar-
coplasm of cardiomyocytes. To do this, a) B-adrenoblockers and b) blockersof
ca-channe
Ca-cha™™ ls are used.

when does extra-myocardial heart failure develop? What compensatory

mechanisms are being turned on in this condition?

gxtra-myocardial insufficiency develops in those cases when (a) little blood

flows through the veins to the heart or when (b) the latter is not able to take all the
incoming blood. The first is observed with hypovolemia (blood loss) or sudden va-
sodilation (collapse) the second - with the accumulation of fluid in the pericardial
cavity which causes difficulty in widening the cavities during diastole.
— Accumulation of fiuid quickl
if the pericardial cavity can occur y
and slowly.
Rapid accumulation occurs as a result a) of hemorrhage during injury or rup-
of the t, b) with rapidly developing pericarditis. Due to the poor extensi-
turéhear
bility of the pericardium, the pressure in the cavity increases, which prevents dia-
stolic dilation of the heart, an acute tamponade of the heart arises. As a result, the
blood filling of the heart cavities decreases, the stroke volume and blood pressure
CTY is a clear inverse relationship between these indicators and intrap-
gricardial pressure: the higher the pressure inside the pericardium, the lower the
blood pressure. Venous pressure increases.
The activation of compensatory mechanisms @ purcadior reflexively
with the participation of signals coming from three receptor fields: (1) caval and
pulmonary veins — increased pressure on the inflow pathways; (2) aorta and carot-
id sinuses (sinocarotid zones) — a decrease in pressure on the outflow pathways
and a subsequent decrease in the reflex depressor effect; (3) pericardium irritated
bythe intrapericardial pressure. With cardiac tamponade, mobilization of powerful
compensation mechanisms, which lead to increased heart contractions (homeo-
* Metric and heterometric mechanisms, inotropic effect of catecholamines), is inef-
ective or impossible. Therefore, only a comparatively low-power and energetically
wasteful mechanism works for compensating and maintain ingin-
blood pressure
heart rate to which the peripheral vessel constriction is then joined.
thesing
trea
al of acute cardiac tamponade.
severe niccourse
This explains the cli
With a slower accumulation of fluid in the pericardium, the work of the com-
Rensatory mechanisms is more effective, so that an increase in intrapericardial
a olre can be compensated for some time. Slow accumulation of fluid, which
; Served in chronic exudative pericarditis and hydropericardium, is accompa-
Pia bya gradual stretching of the pericardium and an increase in the volume of
relat cardial sac. As a result, the change of pressure i ericardium is
ong little and the disturbance of blood circulatioh does not occunfor a lon Qa |
o
(Lg

«
What changes in parameters of cardiodynamics and hemodynamics ,
characteristic for heart failure? Jarosz

With cardiac decompensation, the cardiodynamics parameters change ag fol

| PTY
 elativels tm Pieosuit tis
AS a result, the chaOfnge ny Fee
me little and the disturbance of blood circulz ion does not occutfo a long

323
—

an
What changes in parameters of cardiodynamics and hemodynamics
characteristic for heart failure? Ld

With cardiac decompensation, the cardiodynamics parameters change ag fol-

lows:
1) the stroke volume decreases;
2) the end-systolic volume increases;
3) the end-di ic volume incr S;
4) the end-diastolic pressure rises, as a result of which myogenic dilatation of
e heart develops;
5) the heart rate increases. Tachycardia develops reflexively as a result of
stimul
of the ation
stretch receptors due to an increase in central venous pressure
(Bainbridge reflex). These receptors are in both atria at the venoatrial junctions.
In addition, the direct excitation of cells of the
. . . 3
sinoatrial node by increased blood
T —
pressure in the cavity of the right atrium is also important.
Hemodynamic disorders are characterized by the following changes:
1) the cardiac output (minute volume of blood) decreases;
2) if the heart failure develops according to the left ventricular type, then:
a) blood pressure in the systemic circulation decreases;
b) the total peripheral resistance increases (a reaction aimed at reducing the
fall in blood pressure);
¢) blood pressure in the pulmonary circulation increases. Pulmonary hyper-
tension leading to stagnation of blood in the lungs develops.
3) if heart failure develops in the right ventricle type, then:
a) blood pressure in the pulmonary circulation decreases;
b) the resistance of the pulmonary vessels increases;
¢) central venous pressure increases. Stagnation of blood in a systemic cir-
culation occurs.
4) the volume of circulating blood increases — hypervolemia develops. It is the
result of water retention in the body and polycythemia.

What are the clinical syndromes and signs of heart failure?

1. Circulatory hypoxia (see lesson 27).
2. Dyspnea. Its development is caused by:
a) the effect of an excess of hydrogen ions on the chemoreceptors of the
vessels and directly on the respiratory center,
b) swelling of the interstitial tissue of the lungs and the associated exci
tation of J-receptors (see lesson 26).
3. Cyanosis. It is caused by an increase in the concentration of reduced hemo"
globin as a result of more complete oxygen extraction by tissues. |
4. Edema. With right ventricular failure, edema of the lower half of the body
develops; with left ventricular failure, interstitial lung edema (cardiac asthma y™ |
2 drome) or alveolar edema (pulmon. ma syndrome) occur. !
3

: cardiaciac cirr
cirrhosi
hosiss oof the liver
ver. It Is characteristic for right ve
Ct . is mani : fa
he eart a ~~ \ Nn and portal hvnerten
 ©) CEU al VEIiVUO PI Cooll EC I Cae. Slay a NN Ig y)yeteny
culation occurs. ’
4) the volume of circulating blood increases — hypervolemia develops. It is the
result of water retention in the body and polycythemia.

What are the clinical syndromes and signs of heart failure?

1. Circulatory hypoxia (see lesson 27).
2. Dyspnea. Its development is caused by:
a) the effect of an excess of hydrogen ions on the chemoreceptors of the
vessels and directly on the respiratory center; )
b) swelling of the interstitial tissue of the lungs and the associated excr
tation of J-receptors (see lesson 26).
3. Cyanosis. It is caused by an increase in the concentration of reduced hemo"
globin as a result of more complete oxygen extraction by tissues.
4. Edema. With right ventricular failure, edema of the lower half of the body
develops; with left ventricular failure, interstitial lung edema (cardiac asthma sy™ |
g drome)or qiveciar core (iinet Teg eine) ook:
m

iac cirrhosis o
5. cardiac cirrhosis of the liver. It Is characteristic for right ventricular failure
is manifested by i :
of the J lesson 30). yi n and portal hypertension
. Violations of the acid-base balance. The foll
gE ° o wing variants are possible:
a) non-respiratory acidosis. It is due to the acid metabolites, in particular
lactic acid, that accumulate in the blood
in hypoxia;
by re spiratory acidosis. It may be
a manifestation of alveolar edema
of the
lungs. As a result of developing respiratory failure, hypercapnia appears;
¢) non-respiratory alkalosis. It may be the result of secondary hyparaldoste-
ronism and hypokalemia connected with it;
d) respiratory alkalosis. It may be a consequence of the reflex dyspnea,
which leads to hypocapnia.
7. Secondary hyperaldosteronism (see lesson 33). It causes electrolyte disor- —
ders in the body — (a) hypernatremia, (b) hyperhydration, (c) hypokalemia.
8. polycythemic hypervolemia (see lesson 15).

Lesson 24. Insufficiency of the coronary circulation.

cardiac ischemia

What are the features of coronary circulation in the heart?

1. High level of oxygen extraction in the capillaries of the heart. In the heart
70-75% of 0, coming from arterial blood is extracted in the heart, while in the
brain tissue, skeletal muscle and liver, and kidneys it amounts to 25 %, about 20 %
and 10 % respectively. The high level of O, extraction in the heart is due to the con-
siderable length of its capillaries and, as a consequence, the large time of contact
of blood with the wall of the capillaries.
With an increase in the need of the heart in oxygen, it cannot be satisfied with
an increase in extraction of 0, (as in skeletal muscles) since this parameter is at
the maximum level evenirrefore=r—eretresmeren
mre sed energy needs
 i
i ation
Lesson 24. Insufficiency of the coro nary ry circul
:
cardiiacac iischemia

What are the features of coronary circulation in the heart?

1. High level of oxygen extraction in the capillaries of the heart. In the heart
70-75% of 0, coming from arterial blood is extracted in the heart while in th
brain tissue, skeletal muscle and liver, and kidneys it amounts to 25 % about 20 .
and 10 % respectively. The high level of O, extraction in the heart is due to the con-
siderable length of its capillaries and, as a consequence, the large time of contact
of blood with the wall of the capillaries. *
With an increase in the need of the heart in oxygen, it cannot be satisfied with
an increase in extraction of 0, (as in skeletal muscles) since this parameter is at
the maximum level even at rest. Therefore, to ensure the increased energy needs
of the heart, there is only one way - an increase in the coronary blood flow.
wo 2. High basal tone of coronary vessels. At rest, it makes it possible to provide
ronary blood flow at a level of 250-300 ml / min, which is about 5 % of the min-
ute volume of blood.
i high basal tone of the coronary vessels determines the high reserve of
i Eon So, with a decrease in the basal tone of the heart vessels, the
. 4 the coronary blood flow can increase by 7-10 times.
- The phase character of the coronary blood flow that is associated with the pe-
:
h o the cardiac cycle. During systole, the intramural vessels are compressed —
riods
the bj
digg flow isiminimal and is about 615%
15 % oftofthe total coronary blood flow. During
3 the compression of vessels stops and the blood flow becomes maximum

325
of the total).

Tu

The phase character of the coronary blood flow is most pronounced in the gp,
sion of the vesselg
endocardial zone of the myocardium (the greatest compres )
less
and is prono unced in the subepicardial zone.
circulati
4. Subordination of the coronary on c needs of the hea,
to the metaboli
and its relative independence fom neve b FERCC CICTS In conditions of pg.
coronary vessels
sensitivity of
thology, this subordination is often violated and the
to nerve impulses increases. vessels to a decrease in the Oxygen
5. Exceptionally high sensitivity of coronary 5% antlyp.
pO, arterial blood by
of n only ific
sign
tension in the blood. Reductio
blood flow.
creases the intensity of the corona
6. Insuffici ent develop ment of collatera l vessels. Under adverse conditions, cof.
laterals in the heart cannot compensate for the corona blood flow disturbances.
!
ally inadequate.
so the collateral circulation here is function

How is coronary circulation regulated?

autoregulation, (b)
In the regulation of the coronary circulation, (a) myogenic
(c) nerve regulati on may be disting uished.
metabolic and
effect, according to which
1. Myogenic autoregulation. Its basis is the Bayliss
increas es the force of their
the stretching of the smooth muscles of blood vessels
Frank Starling law for the heart). y
contraction (an analogue of theensures blood flow
Myogenic autoregulation the permanence of the coronar
e. So, with increasing
and its relative independence from changes in blood pressur
+ the otretching of the smooth muscle cells of the coro-
 The phase character of the coronary blood flow is most pronounced in the sy,
endocardia zone lof the myocardium (the greatest compression of the vessels)
pronounced in the sube icardial zone.
and is less
4. Subordination of the coronary circulation to the metabolic needs tionsof the hey,
influ ences . In condi of ps.
and its relativeindependens from nerve regulatory
tivity of coronary vessels.
thology, this subordination is often violated and the sensi
to nerve impu i ses.
els to a decrease in the Oxygen
5. Exceptionally high sensitivi ty of coronary vess
tension in the blood. Reductio n of pO, arterial blood by only 5% significantly ip.
d flow.
creases the intensityof the coronary bloo
rse conditions, co-
6. Insufficient development of collateral vessels. Under adve
nary blood flow disturbances
laterals in the heart cannot compens ate for the coro
inadequate.
so the collateral circulation here is functionally

How is coronary circulation regulated?

autoregulation, (b)
In the regulation of the coronary circulation, (a) myogenic
distinguished.
metabolic and (c) nerve regulation may be
1M nic ation. Its basis is the Bayliss effect, according to which
ases the force of their
the stretching of the smooth muscles of blood vessels incre
law for the heart).
contraction (an analogue of the Frank-Starling
of the coronary blood flow
Myogenic autoregulation ensures the permanence
ure. So, with increasing
and its relative independence from changes in blood press
h muscle cells of the coro-
blood pressure in the aorta, the stretching of the smoot
ase of arterial tonus
nary arteries increases, which leads to their contraction, incre
of blood pressure, the
and preservation of blood flow constancy. With a decrease
ation of smooth muscles
coronary blood flow is maintained constant due to relax
and dilatation of the arteries.
of the vessels are
At present, it is shown that when the smooth muscle cells
to calcium ions increases.
stretched, the permeability of their plasma membrane
The latter penetrate into the cells and cause their contraction.
to the met-
2. Metabolic regulation. It subordinates the coronary circulation
of a number of ions
abolic needs of the heart. It is carried out with the help
lactic acid, prosta-
and metabolites, among which ions of hydrogen, potassium,
tant: (a)a
glandins are distinguished. However, two factors are the most impor
latter is
decrease in the O, tension in the arterial blood and (b) adenosine. The an
g hypoxia
formed as a result of the hydrolysis of adenine nucleotides durin
of Ca-channels, adenos’
with enhanced cardiac function. Being a natural blocker
of smooth muscle cells of
ine reduces the entry of Ca?* ions into the cytoplasm
ases and the
coronary vessels. As a result, the degree of their contraction decre
ary blood flow
basal tonus diminishes. Therefore, coronary vessels dilate, coron
increases (Fig. 96).
3. Nervous regulation. Neurogenic tonus of the coronary vessels
is insignif
ry
cant, as evidenced by an almost complete absen ce of changes in the corona
ct effect
The indire
blood flow after complete denervation of the heart vessels.
326

p—
 Arteriole

poem

ATP — ADP — AMP — Adenosine

t
Increased Suppression
ATP hydrolysis of ATP resynthesis
A \

Enchanced H !
heart working FRO

Fig. 96. One of the mechanisms in metabolic regulation of the coronary circulation

of the nervous system on the coronary blood flow is much more important. It is
carried out through changes in the work of the heart and the intensity of metab-
olismin it.
The possibility of direct influence of the nerves on the tonus of the coronary
vessels is shown in the experiment. Thus, with the irritation of parasympathetic ]
nerves and the introduction of acetylcholine, there is a slight dilatation of the cor-
onary arteries. Mediators of the sympathetic nervous system (catecholamines)
when act on a-adrenoreceptors cause vasoconstriction, while vasodilatation is
caused when B-adrenergic receptors are acted upon. Since B-adrenoreceptors
predominate in the coronary vessels, the overall effect of sympathetic influences
is a slight expansion of the heart vessels.

What is the insufficiency of the coronary circulation? What is the

difference between relative and absolute coronary insufficiency?

Insufficiency of the coronary circulation is a pathological condition character-

ized by the inability of the coronary vessels to provide blood supply to the heart in
accordance with its energy needs. In other words, there is a discrepancy between
the energy needs of the heart and the delivery of oxygen and nutrients by the cor-
onary vessels.
Insufficiency of the coronary circulation can be (a) relative and (b) absolute.
Relative coronary insufficiency arises in the case of a primary increase in the
energy needs of the heart (increased load on the heart during physical work, hyper-
tension). At the same time, the intensity of the coronary blood flow may increase
but this is insufficient to meet the increased needs of the heart.
Absolute coronary insufficiency occurs in the case of a primary impairment of
the Coronary circulation, as a result of which the delivery of oxygen and nutrients
the Myocardium is reduced both at rest and at an increase in the energy needs ~
oN
Of the heart. ™
 —
What pathogenetic factors can determine the development of absojy,
failure of the coronary circulation?

The intensity of the coronary circulation is determined by the formula

where Q is the volumetric rate of coronary blood flow; P,, and P,, — blood pressyre.
respectively, in the beginning and at the end of the coronary vascular system, (P, -
P,.,) — perfusion pressure; R - resistance of coronary vessels.

Since absolute coronary insufficiency is characterized by a decrease in the

coronary blood flow (a decrease in Q), two pathogenetic variants of its develop
ment are possible.
|. Decreased perfusion pressure. In this case, coronary insufficiency of the cep.
tral origin develops. Its reasons may be:
a) arterial hypotension (decrease in Part), for example, in all types of
shock, aortic valve insufficiency. With a decrease in blood pressure, the
mechanisms of myogenic autoregulation of the coronary blood flow
are triggered supporting blood supply at a constant level. However,
when the blood pressure falls below 70 mm Hg, these mechanisms are
insufficient;
b) disturbance of venous outflow (increase of Rven). In the experiment, it
ismodeled by ligating the veins of the heart. This mechanism can be
important in decompensated right ventricular failure when the central
venous and end-diastolic pressure increases.
Il. Increased resistance of coronary vessels. Coronary insufficiency of local or-
igin develops. Because the

where n is the viscosity of the blood; / is the length of the vessels; r is the radius of
the vessels, the increase in vascular resistance may be due to:

a) an increase in the viscosity of the blood in violation of its rheological prop

erties (dehydration, polycythemia, DIC syndrome). In this case, microcircy:
latory disturbances develop, up to the sludge syndrome and true capillary
stasis (see lesson 8);
b) a decrease in the radius of the vessels. This is the main factor in the dé
velopment of absolute coronary insufficiency. It causes ischemia of the
heart.
328
 |
pp

[24.5] What mechanisms can underlie the development of myocardial

ischemia?
|. Obturation mechanism ~ reduction of the lumen of the coronary arteri
es. Its
reasons may be:
a) stenosing atherosclerosis (the cause of myocardial ischemia
in 90 % of
cases);
b) thrombosis of the coronary arteries (most often a consequenc
e of athero-
sclerosis);
c) embolism of the coronary arteries;
d) inflammatory processes in the wall of the blood vessels - corona
ritis. It
can be the manifestation of rheumatism, syphilis.
For the development of clinical signs of myocardial ischemia, the value of “crit-
ical stenosis” is important. This is a minimal decrease in the lumen of the vessels,
in which ischemia occurs. In humans, this figure is 75 % (in pigs and dogs this
figure is less and more respectively).
II. Angiospastic mechanism - spasm of coronary arteries. Its causes can be:
a) stimulation of a-adrenergic receptors against the background of block-
ade of B-adrenergic ones;
b) vasopressin;
c) angiotensin Il;
d) thromboxane A,;
e) hypocapnia;
e) endothelin — a biologically active substance of endothelial origin.
The clinical form of coronary angiospasm is known as Prinzmetal angina.
lll. Compression mechanism. It can occur with tachycardia (the total duration of
the period of compression of the coronary vessels increases during the systole of the
heart). Sometimes scars and tumors can be the cause. In the experiment it is used to
model ischemia and myocardial infarction by ligation of the coronary arteries.

24.6. What pathogenetic factors affect the myocardium

in conditions
of coronary insufficiency?

1) hypoxia;
2) acidosis. It develops as a result of the accumulation of acid metabolic prod-
ucts due to the violation of blood outflow and the activation of glycol
ysis;
3) increase in the extracellular concentration of potassium ions in the ischemic
Zone. Itis detected from the very beginning of the coronary circulati imp
on airment
(in a few minutes) when there is still no damage to the cardiomyocytes. During
this Period, the passive release of potassium ions from the cells takes pla
ce (pos-
Sibly there is an increase in the permeability of K-channels), and its ext
racellular
Concentration increases to 8 mmol/l and more. After a few hours the “leaka
ge” of
Bo from the cells may be due to a disruption in the work of Na-K-pumps (ATP
'clency) and an increase in the permeability of damaged membranes.
29
 What consequences for the myocardium can failure of the corona
circulation have? K

1) impaired contractility of the myocardium with the development of heart f,;

2) the appearance of abnormal electrical activity — electrical instability oo e
heart, the development of arrhythmias;
n 8);
3) damage to cardiomyocytes due to ischemia (see lesso
4) reperfusion syndrome.

What violations of the contractile function of the myocardium can occyr

with its ischemia?

In myocardial ischemia (a) early and (b) late violations of its contractile func.
tion are distinguished.
Early disturbances occur very early, even with a slight deficit of ATP. They relate
to the hypocalcic variant of contractility disorders (see question 23.38) and de-
omyocytes. The
velop as a result of Ca-channel blockade of sarcolemma in cardi
has at least
violation of the conductivity of Ca-channels under ischemic conditions
two mechanisms:
l proteins;
a) deficiency of ATP — disruption of phosphorylation of Ca-channe
— direct block-
b) activation of glycolysis — accumu lation of H* ion in the cells
ade of Ca-channels.
in the entry of Ca** ions into
The consequence of these disorders is a decrease
electromechanical coupling
the sarcoplasm of muscle fibers, the disorder of an
iomyocytes.
and a decrease in the force of contractions of card
prolonged disorders of the coro-
Late disturbances of contractility occur with
nary blood flow — more than 30 minutes. They refer to a hypercalcic (contracture)
n of calcium ions in the sarco-
type of contractility disorders. The concentratio
main reasons:
plasm of cardiomyocytes increases due to two to ATP deficiency,
sarcoplasm due
a) disruption of removal of Ca?" ions from
le fibers through the damaged
b) increase in the entering of Ca?" ions into musc
plasma membrane of the cells.
the relaxation of cardiomyo
As a result of an increase in the content of Ca? se
s is dist urbe d, over -con trac tion of myof ibri ls (contr. actura) occurs, and con
cyte
quently, the contractility of the heart is disordered.

nt of arrhythmias in
YX What mechanisms can determine the developme
myocardial ischemia?
the
of arrh ythm ias is asso ciat ed with el ec tr ical instability of in
The occurrence
rs a few minu tes after the onse t of myocardial ischemia. Its m3ich
heart which occu ytes, as a result of 0 ’
e of po ta ss ium io ns from cardio i myoc
re le as za!®®
uses partial depolari
cause is the ium i
ula r con cen tra tio n inc rea ses . Th is ca
their extracell in the con
of nea rby cell s. Dep end ing on the level of increase
| © the sarcolemma ssible:
owing consequences are po
| 9 of extracellular potassium, the foll
}

325 of 522
E
»
ion of extracellular po-
areas of the myocardium, where the concentrat s from
potential decrease
rd sium increases to 8 mmol/l, the membrane poten-
poe mV to -80 mV approaching the level of the critical depolarization
the rate of the impulse conduc-
tial. Therefore, the excitability of cells and
tion in these areas increase; lar concentr ation 0
b) in the areas of the myocardium, where the extracellu
of muscle fibers be-
potassium exceeds 8 mmol/l, the membrane potential
els decreases (their
comes less than -80 mV, the conductivity of Na-chann
excitability of cardiomyo-
inactivation occurs) resulting in a decrease in the
cytes and the rate of impulse conduction. oo
rent
simultaneous existence of different parts of the myocardium with diffe
in excitability and conduc-
es of electrophysiological disturbances (an increase
the other hand) creates conditions for
tion on the one hand, and their decrease on
lead to the development of ven-
the realization of re-entry mechanism, which can
questions 23.25 and 23.27).
tricular fluttering and fibrillation leading to death (see is the main
ventricular fibrillation, which occurs with myocardial ischemia,
cause of the so-called sudden death. At the same time, no signs of ischemic myo-
cardial damage are found on the autopsy.

What is a reperfusion syndrome? What is its essence? What are the

mechanisms of its development?

Reperfusion syndrome arises after renewing blood flow in the ischemic area of
the myocardium, i.e. as a result of reperfusion.
Renewal of the coronary circulation may be due to (a) cessation of coronary
angiospasm, (b) lysis of the thrombus, (c) destruction of aggregates of blood cells,
(d) surgical removal of thrombus, and (e) removal of ligature.
Clinically, the reperfusion syndrome is manifested by a significant increase
in the intensity of myocardial damage immediately after the resumption of the
coronary blood flow. As a result, the patient's condition deteriorates sharply. The
minimum duration of ischemia, after which a pronounced reperfusion syndrome
occurs, is 40 minutes. If the duration of ischemia is less than 20 minutes, this
syndrome does not develop (this duration is typical for angina attacks). With a
duration of ischemia of 20-40 minutes, reperfusion injury of the heart can some-
times occur,
The pathogenetic basis of the reperfusion syndrome is the so-called “oxygen
cok The essence of the phenomenon is as follows. If the heart is perfused
Pi) iy that does not contain oxygen (or contains itina little amount), and
Kp minutes or more, the perfusion is continued with a solution with a normal
d in then asa result of such perfusion, the disturbances, which have been
but b y the previous hypoxia, do not only decrease, as it should be expected,
actiy atiecome more pronounced
entry (paradox!). The basis of this paradox is a sharp
on of free radica
.
l oxida
.
tion
.
(oxid: ative
:
stress, see lesson 7) caused by the
of the 9a, into the cells that contain a large number of reduced components
Piratory chain. There is a dropping of electrons directly to oxygen mole-
 cules bypassing the respiratory chain, as a result of which a large number of ¢
radicals are formed. The latter initiate reactions of free radical oxidation i,
. Cludip
lipid peroxidation, which are an important molecular mechanism of damage to ca
membranes (see lesson 7).

What is ischemic heart disease? What are its clinical forms?

Ischemic heart disease (IHD), also called coronary heart disease, is 3 disease
that develops as a result of absolute failure of the coronary circulation and jg man.
ifested by damage to the myocardium of varying degrees.
Its main clinical forms are:
1. Angina pectoris (stenocardia) — short-term (up to 20 min) acute corona
insufficiency accompanied by pain syndrome, a sense of fear and associateq veg
etative reactions.
There are (a) exertional angina, (b) angina at rest, (c) Prinzmetal angina (coro-
nary artery spasm), (d) various forms of unstable angina;
2. Pre-infarction condition (intermediate coronary syndrome, or acute focal
dystrophy of the myocardium). It develops with the duration of myocardial isch.
emia from 20 to 40 min.
3. Myocardial infarction - necrosis of the heart muscle caused by violations of
the coronary circulation. It occurs with reversible (transient) ischemia, which lasts
for more than 40-60 minutes, or with irreversible disturbances of coronary blood
flow.
4. Cardiosclerosis - sclerotic changes in the heart muscle. They can be diffuse
(atherosclerotic cardiosclerosis) and focal (postinfarction cardiosclerosis).
In addition, as a form of IHD, sudden coronary death (primary cardiac arrest) is
isolated. Its cause, as a rule, is the electrical instability of the heart accompanied
by the development of coronary insufficiency (see above). The organism can be
withdrawn from the state of clinical death, caused by cardiac arrest, by means of
resuscitation. If this is not done, then death comes.
In clinical practice, the term acute coronary syndrome is used to quickly decide
on the tactics of treatment. It includes such forms of IHD as unstable angina,
acute myocardial infarction and sudden coronary death.

What are the main causes of myocardial infarction?

1. Atherosclerosis of the coronary arteries (see lesson 25). Due to the rupture
of the atherosclerotic plaque and the formation of a thrombus on its surface, 0C
clusion of the coronary artery occurs which leads to the cessation of oxygen
Sup”
ply to the corresponding site of the myocardium.
2. Increased load on the heart (physical exertion, hypertension). This increases
the need for oxygen by the heart.
3. Stress (see lesson 33).
332

327 of 522
 what is the role of catecholamines in the
; genesis
pathogenesi of myocardial
infarction”
ab the® development of myocardial infarction , the following
a have significance i effects of catechol-

1. Disturbance of the coronary circulation. This is due to the fact that catechol-
mines:
? a) contribute to the development of atherosclerosis (stress and catechol-
amines, which take partin its realization, are a risk factor for this disease);
b) cause an over-constriction (Contractura) of the smooth muscles of the cor-
onary arteries. Itis a result of injury to the vascular cells by catecholamines;
¢) activate thrombus formation and blood clotting
2. Increased need of the heart in oxygen. Energy needs of the heart are increased
asa result of positive inotropic and chronotropic effects of catecholamines and a
rise of the total peripheral resistance, which increases the load on the heart
3. Non-coronary catecholamine damage to cardiomyocytes. They are not asso-
ciated with a violation of the coronary circulation. They occur because the large
doses of catecholamines activate lipid and calcium mechanisms of cell damage
(see lesson 7).

[24.14] What clinical syndromes are typical for myocardial infarction?

1. Pain syndrome.
2. Acute heart failure. It develops when large areas of the myocardium are
affected. It may be manifested as a syndrome of cardiac asthma and pulmonary
edema or cardiogenic shock.
3. Arrhythmic syndrome. The development of all types of arrhythmias is possi-
ble. The most dangerous is the appearance of ventricular fibrillation.
4. Resorption-necrotic syndrome.

What are the mechanisms and significance of pain syndrome in

myocardial infarction?

The development of pain syndrome in necrosis of the heart is explained by:

ions,
a) chemical factors that appear in tissues when cells are damaged. H*, K*
prostaglandins and lysosomal enzymes are among them;
myocar-
b) changes in the contractile properties of the ischemic portion of the
dium resulting in a pathological stretching (prolapse) of the heart wall as it
contracts. This leads to the excitation of the mechanoreceptors of the heart
and the development of pain.
myocardial infarction is
i J pathogenetic significance of the pain syndr ome in
sympathoad-
5 1- Pain is a powerful factor in initiating stress and activating the
this case contribute to
"al system . Large doses of catecholamines released in
333

m
Yocardial damage (see question 24.13);
N

H |
 |
2. Severe pain causes excitation first and then overexcitation of vita) Ceny
the brain (respiratory, cardiovascular). This circumstance is an iMportan fag
the development of cardiogenic shock. Or;
\

| PRIA What is cardiogenic shock? In what forms can it manifest itself

| Cardiogenic shock is a shock that occurs as a result of a sharp drop |

pumping function of the heart. It is the most dangerous complication of Myoe, ®
al infarction, often leading to death. Idi.
There are 4 forms of cardiogenic shock.
1. Reflex form (pain shock). The main mechanism of its developmen iSpy
longed pain which causes the activation of the sympathoadrenal
System, typ;
into its inhibition. This leads to depression of the contra
ctile function of the hea
bradycardia, a decrease in the tonus of the peripheral vessels and a drop in bloog
pressure.
)
2. Hypokinetic form (true cardiogenic shock). The main fact
or of its develo
ment is a sharp decrease in the contractile function of
I the heart ag a result
ischemic damage to cardiomyocytes. A true cardiogenic shock develops when,
I area of the affected myocardium exceeds 40 %.
fl 3. The dyskinetic form. It occurs as a result of asynergi
| ; a (mismatch) of the
fl myocardium contractions. The reason for this asyne :
rgy Is gross damage to the
i heart (aneurysm, rupture of the interventricular
i! septum, separation of the chord
valves).
i 4. Arrhythmic form. It is a consequence of severe arrhy
thmias.

[| What is the pathogenesis of cardiogenic shock?

In the pathogenesis of cardiogenic shock several
stages are distinguished.
Stage | - the initial drop in blood pressure. All pathogen
ic factors of cardiogenic
shock (reflex depression, increase in the area of
damaged myocardium, asynergy
of the heart, arrhythmia) cause a decrease in the card
iac output. This, according to
the laws of hemodynamics, leads to a decr
ease in blood pressure.
Stage Il - compensatory spasm of arterioles. It is char
acterized by the activa:
tion of the sympathoadrenal system, the release of
catecholamines, vasopressin
i glucocorticoids, and the formation of angiotensin Il. The
release of powerful v&
| soconstrictors causes a generalized spasm of arterioles resulting
in an increasé
| in the total peripheral resistance. This reaction is
compensatory and is aimed a
preventing further fall in blood pressure.
{ Stage Ill - secondary fall in blood pressure. Prolonged spasm
of arterioles In
peripheral tissues causes disturbance of microcircula
tion and hypoxia. The com
sequences of oxygen starvation are:
a) acidosis, which causes depression of the contr
actile function of the ™”
cardium;
es
b) the dilatation of arterioles resulting from the accumulation in the
of metabolites-
iS”
vasodilators (‘metabolic sympatholysis®);
|
- —Ry
 ~~ q
c) ately he myocenemic toxins from the tissues
m 2) rdial depression
into the blood
factor, , which Which i
the pancreas, is of great pathogenetic
importance ? released from
All these changes worsen the contractile function
of the heart and “remove”
the compensatory spasm of arterioles, therefore causing a further drop in blood
ressure. )
stage IV - terminal changes. As a result of 3 significant drop in blood
pressure
(below 40mm Hg):
a) coronary circulation 'S even more disturbed and myocardial
ischemia in-
creas
es — the impairement of contractile function of the myoc
ardium pro-
gresses;
b) acute renal failure develops (glomerular filtration completely stops;
anuria
and intoxication occur);
c) the cerebral circulation is disturbed, hypoxia of the brain develops, the vital
centers function is inhibited.
The complex of these changes leads to death.

What is the essence of the resorption-necrotic syndrome that develops

with myocardial infarction?

Resorption-necrotic syndrome in myocardial infarction is the consequence of

the entry of decaying products of necrotic tissue of the heart into the blood. It
manifests itself as follows:
a) fever (see lesson 10);
b) neutrophilic leukocytosis;
¢) an increase in the erythrocyte sedimentation rate (ESR);
d) enzymemia - the appearance of enzymes from damaged cardiomyocytes
(creatine kinase, aspartate aminotransferase, lactate dehydrogenase |
type, etc.) in the blood;
e) autoimmune syndrome (Dressler’s syndrome). It develops as a result of
conformational changes in myocardial proteins. It is manifested by in-
flammation of the serous membranes of the body - polyserositis (pericar-
ditis, pleuritis, peritonitis).

24.19 | What is non-coronary heart necrosis? How are they modeled in the
experiment?

Non-coronary necrosis of the heart arises not as a result of insufficiency of the

Coronary circulation, but for other reasons.
There are 3 number of experimental models of such necrosis.
- Hypoxic necrosis of the myocardium. It can be reproduced with the help of
'0US types of hypoxia: hypoxic, hemic (see lesson 27). In this case, necrotic
rige to the muscle fibers of the heart develops against the background of gen-
"al lack of oxygen in the body, which in itself leads to an increase in the load on wn
™
€ Circulatory system. m™m

330 of 522
 centers function Is inhibited.
The complex of these changes leads to death.

What is the
ZEENmyocardial
with essence of the resorption-necrotic syndrome that develops
infarction?

Resorption-necrotic syndrome in myocardial infarction is the consequence of

the entry of decaying products of necrotic tissue of the heart into the blood. It
manifests itself as follows:
a) fever (see lesson 10);
b) neutrophilic leukocytosis;
¢) an increase in the erythrocyte sedimentation rate (ESR);
d) enzymemia - the appearance of enzymes from damaged cardiomyocytes
(creatine kinase, aspartate aminotransferase, lactate dehydrogenase |
type, etc.) in the blood;
e) autoimmune syndrome (Dressler’s syndrome). It develops as a result of
conformational changes in myocardial proteins. It is manifested by in-
flammation of the serous membranes of the body - polyserositis (pericar-
ditis, pleuritis, peritonitis).

| 24.19 | What is non-coronary heart necrosis? How are they modeled in the
experiment?

Non-coronary necrosis of the heart arises not as a result of insufficiency of the

coronary circulation, but for other reasons.
re are a number of experimental models of such necrosis.
1 Hypoxic necrosis of the myocardium. It can be reproduced with the help of
Probing types of hypoxia: hypoxic, hemic (see lesson 27). In this case, necrotic
Mage to the muscle fibers of the heart develops against the background of gen-
tek of oxygen in the body, which in itself leads to an increase in the load on

335
"Culatory system.

2. Electrolyte-steroid cardiopathy with necrosis. With the introduction of a large

amount of sodium salts (sulfates, phosphates) to rats, foci of damage and necro-
sis in the myocardium appear. They are often accompanied by the hyalinosis of
the vessels in other organs. These lesions become more extensive or occur with
the introduction of fewer salts if some steroid hormones of the adrenal glands =
(mineralocorticoids) are simultaneously administered.
3. Immune damage to the heart is possible when introducing a heterogeneous
serum into the body of an experimental animal. The serum should contain anti-
bodies against the heart proteins of an animal of this species (cardiac cytotoxins).
It has also been proven that in certain situations the antibodies and sensitized
lymphocytes directed against the tissues of their own heart and having a damag-
ing effect may appear in the body (autoimmune reactions, see lesson 6).
4. Neurogenic heart disease. Dystrophic c\hanges and necrosis of the myocar-
dium can be caused by acute or chronic stimulation of the cervical-thoracic gan-
glia of the sympathetic trunk, vagus nerve, hypothalamus, cerebral trunk or other
parts of the brain. The mechanism of neurogenic lesions is based on a discrepan-
cy between the levels of function, metabolism and blood supply of the heart. Irri-
tation of the cardiac sympathetic nerves is accompanied by a significant increase
in myocardial oxygen consumption in comparison with the insufficient increase in
the coronary blood flow. As a result, hypoxia of the myocardium develops.