Section 2 Cardiovascular Physiology
Chapter
Cardiovascular physiology applied to critical
12 care and anesthesia
Nils Siegenthaler and Karim Bendjelid
Introduction
Hemodynamic management of the patient in a
perioperative setting and especially in intensive care
is considered a cornerstone of patient treatment.1,2
Guidelines and protocols provide a standard basis
for the management of such patients. However,
mastering the cardiovascular physiology, and identi-
fying the pathophysiological mechanisms and arche-
types involved, allow the clinician to manage each
situation according to the specific characteristics of
the state of the patient. Moreover, implementation of
hemodynamic monitoring at the bedside faces many
challenges.
Monitoring devices and hemodynamic markers
assessed at the bedside have evolved significantly over
the last 30 years, resulting in the availability of a large
variety of methods and procedures with specific fea-
tures and limitations. In the present setting, adequate
use of these devices and machines requires a full
knowledge of the concepts used to obtain the meas-
ured parameters. Thus, in order to guide therapy,
physician skills should be based on physiological con-
cepts rather than on simple guidelines.3,4 Indeed, no
hemodynamic monitoring, per se, has been associated
with an improvement in patient survival5–9 unless
integrated in an early and clinically relevant therapy.1
Finally, the habitually measured macrohemodynamic
parameters may not always allow assessment of tissue
perfusion. Indeed, in some circumstances, macrocir-
culatory perfusion may be decoupled from microcir-
culation perfusion, resulting in situations where, even
if macrocirculatory parameters are adequate, tissue
hypoperfusion may persist.10,11
The objective of the present chapter is to describe
the essential physiological mechanisms involved
in the hemodynamic management of patients in a
Perioperative Hemodynamic Monitoring and Goal Directed Therapy, ed. Maxime Cannesson and Rupert Pearse.
Published by Cambridge University Press. © Cambridge University Press 2014.
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perioperative setting and in intensive care. The
chapter was conceived primarily to provide up-to-
date information to anesthesiologists and intensivists
in order to be able to understand adequately meas-
ured hemodynamic parameters and to adapt the
therapy according to the pathophysiological state
of patients.
Hemodynamics and oxygenation
The “Pathway of oxygen,” described previously by the
Swiss biologist ER Weibel, successively combines a
system able to extract oxygen from the atmosphere
and eliminate CO2 produced by the cells, i.e., the
respiratory system. Then, the cardiovascular system
is charged to transport oxygen from the lungs to the
tissues. Within the cells, cellular respiration will use the
oxygen to produce adenosine triphosphate and other
high-energy compounds through aerobic metabolism.
The cardiovascular system can be separated into two
circulations, with specific characteristics, arranged in
series. Macrocirculation, which includes the heart,
arteries and veins, is responsible for the transport
of oxygen to the organs and for the transport of meta-
bolic wastes to their elimination sites. Microcirculation
includes arterioles, capillaries, and venules and ensures
adequate and homogeneous perfusion of tissues. Even if
these two systems are arranged in series, the specificity
of each system means there may be a situation where,
despite one part seeming to operate correctly, the other
one may be altered. This particular state, called macro-
microcirculatory decoupling, explains why in specific
situations, signs of tissue hypoperfusion may persist
despite normalization and optimization of macrohemo-
dynamic parameters.11
The hemodynamic goal of macrocirculation is to
generate an oxygenated blood flow (DO2). DO2 is
95
 Section 2: Cardiovascular Physiology

Critical DO2 Figure 12.1. The relationship between

total cellular consumption of oxygen
(VO2) and the O2 delivery (DO2). In the
supply independent zone, a decrease in
DO2 is compensated by an increase in O2
Oxygen consumption VO2

extraction, which preserves O2 cellular

Decrease the oxygen need without change in O2 consumption.
needs DO2/VO2 relationship
3 A further decrease in DO2, under the
2 critical point of DO2, could not be
compensated by an increase in O2
extraction, and thus will result in a
1
decrease in O2 cellular consumption. Two
Signs of cellular hypoxia therapeutic strategies can allow
Increase the oxygen
delivery
(lactate) the re-equilibration of DO2/VO2
relationship: a decrease in O2 needs or
an increase in DO2. (1) Low DO2/VO2
relationship indicating shock state. (2)
adequate DO2/VO2 relationship. (3) high
Oxygen delivery DO2 DO2/VO2 relationship representing
supra-physiologic resuscitation.

defined as the quantity of oxygen per unit of volume of elevation in the plasmatic concentration of lactate, or
blood (CaO2 ¼ [1.39 × Hb (g.liter 1)] × [SaO2 (%)] + signs of excessive extraction of oxygen (low venous
[(0.23 × PaO2 k Pa 1)]) debited at a rate equivalent blood saturation).
to the cardiac output (CO) in liters per minute (DO2 ¼ Equilibration of DO2/VO2 can be obtained by two
CO × CaO2). DO2 is adequate when the present value methods (Figure 12.1): a decrease in the oxygen
is equivalent to the metabolic oxygen requirement requirement (VO2) or an increase in the oxygen deliv-
(oxygen consumption: VO2). The relationship linking ery (DO2). First, VO2 depends mainly on cellular
DO2 to VO2 presents with two zones (Figure 12.1). metabolism, which may be increased by a rise in
Initially, a decrease in DO2 is compensated by an cellular metabolism (temperature or muscular activ-
increase in extraction of oxygen in order to maintain ity). In a critically ill patient, the respiratory cost of
the aerobic metabolism (zone of supply independ- spontaneous breathing may be important. Field et al.
ency). However, when DO2 decreases further, oxygen estimated the cost of breathing in a patient with
extraction may not be able to compensate for the cardiorespiratory disease to be about 24% of the
decrease in delivery (critical DO2 point) and cells VO2 total, but it may be higher in specific patients.13
suffer from a lack of oxygen, limiting their aerobic Therefore, respiratory support to decrease VO2 may
metabolism, which may result in cellular hypoxia, allow re-equilibration of the DO2/VO2 relationship
ischemia, lactate production, and lastly death (zone until DO2 improves. This concept is especially
of supply dependency) (Figure 12.1). Therefore, important in a patient where a refractory low cardiac
the goal of tissue resuscitation is to use any method output limits the DO2. For example, after a cardio-
possible to balance the relationship between DO2 pulmonary bypass, myocardial function may be tran-
and VO2. A therapeutic management that allows sitorily decreased, limiting DO2. In this case, the
achievement of a high DO2 value (far above VO2) increased cost of breathing during an early weaning
may also result in the situation of supraphysiologic of positive pressure ventilation can be associated with
oxygenation that has been demonstrated to be associ- a DO2/VO2 imbalance, resulting in cellular hypoxia.
ated with an excess of morbidity and mortality The second way to re-equilibrate DO2/VO2 is to
(Figure 12.1).12 The present concept of DO2/VO2 increase DO2 (Figure 12.2). The arterial oxygen
balance applies not only in a global shock state, but content, CaO2, can be optimized by increasing the
also in a situation where local perfusion is altered hemoglobin content or by raising the SaO2. The usual
(intracranial hypertension, cerebral vasospasm, mes- goal is to achieve a hemoglobin concentration
enteric ischemia, intra-abdominal compartment between 7.0 and 9.0 g/dL. SaO2 could be increased
syndrome). Imbalance between DO2/VO2 can be iden- by raising FiO2 or by improving the pulmonary gas
tified by the occurrence of signs of cellular hypoxia exchange (decreasing the pulmonary shunt [zones
(Figure 12.1): organ dysfunction (oliguria, confusion), with low ventilation/perfusion ratio]).

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 Chapter 12: Critical care and anesthesia

Tissue oxygenation

Oxygen
Oxygen delivery consumption
VO2

Macrocirculatory oxygen delivery

DO2 Driving pressure

Upstream Compartment Downstream

CaO2 CO pressure pressure pressure

Heart
Hcrt SaO2 Systolic volume of ejection
rate

Preload Inotropy Afterload

Figure 12.2. Hemodynamic determinants of tissue oxygenation. Tissue oxygenation is adequate when O2 delivery is equilibrated with O2
needs. O2 delivery is determined by the arterial content in oxygen (CaO2 × cardiac output (CO)). The main determinants of CaO2 are the
arterial mass in red cells (Hematocrit: Hcrt) and the O2 arterial hemoglobin saturation (SaO2). CO is determined by the stroke volume multiplied
by the heart rate. The value of preload, inotropy, and afterload influence stroke volume. A sufficient driving pressure across the tissue is
mandatory in order to maintain tissue perfusion. Driving pressure is determined by the upstream pressure (arterial pressure), the downstream
pressure (venous pressure), and the pressure around the tissue.

As optimization of DO2 by SaO2 and hemo-
globin concentration is limited, CO is thus the
main determinant of DO2 in a shock state. CO is
defined as the systolic volume (SV) of ejection
(stroke volume: SV) multiplied by the heart rate
(CO (liter min 1) ¼ SV (liter) × HR (beat min 1))
(Figure 12.2). The three main determinants of SV
are ventricular preload, ventricular inotropy, and
ventricular afterload (or aortic impedance in a pul-
satile system). Each of these determinants will be
discussed separately in the next part of the chapter.
The second determinant of CO is heart rate. Heart
rate must be high enough to ensure CO; however,
an increase in heart rate is at the expense of a
decreased duration of diastole, necessary to gener-
ate enough preload, and is associated with an
increase in myocardial work. Finally, even if a
macrocirculatory oxygenated blood flow is gener-
ated (optimal DO2), it must be transmitted to
arterial and tissue circulation. Therefore, arterial
pressure must be enough to overcome vascular
resistance and downstream pressure, maintaining
an adequate perfusion pressure (blood flow ¼
perfusion pressure/resistance).
Perfusion pressure, often called driving pressure,
depends on upstream pressure (aortic or postarteriolar
pressure for the capillary circulation) and on down-
stream pressure (venous pressure) (Figure 12.3A). In
some cases (intracranial hypertension, abdominal
compartment syndrome, limb compartment syn-
drome), pressure surrounding the tissue is higher
than downstream vascular pressure. In this situation,
similarly to a Starling resistor, the external pressure
will determine driving pressure and thus the flow
across the tissue (Figure 12.3B). Flow can be main-
tained by increasing the arterial pressure (thera-
peutic hypertension) or by lowering the extramural
tissue pressure (decompressive craniectomy,
opening of the abdominal wall, draining excessive
abdominal fluid, fasciotomy). An increase in down-
stream vascular pressure (high central venous pres-
sure) may also limit perfusion pressure and may

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 Section 2: Cardiovascular Physiology

A C
P2 P2

P1 P3 P1 P3

Upstream pressure
Upstream pressure Downstream pressure Downstream pressure

Tissue
Tissue compartment
compartment pressure
pressure

Arteriolar vasoconstriction
B D
P2

P1 P2 P3 Partial P1 P3

Upstream pressure Downstream pressure

Upstream pressure Downstream pressure

Tissue Tissue
compartment compartment
pressure pressure

Figure 12.3. The main hemodynamic determinant of the driving pressure (i.e., pressure allowing perfusion of tissue). Upstream pressure
represents input arterial pressure and downstream pressure represents the outlet venous pressure. The tissue compartment pressure
represents the pressure around the tissue. In a normal situation (A) upstream pressure is higher than downstream pressure, that is higher than
the tissue compartment pressure resulting in a positive, driving pressure allowing tissue perfusion. When the tissue compartment pressure
increases (intracranial hypertension, abdominal compartment, etc.) at a value higher than downstream pressure, the pressure surrounding the
organ determines the flow across the tissue. In the case where the present pressure increases more than the upstream pressure, blood flow
across the tissue ceases. In various situations, such as venous congestion, increasing downstream pressure may also limit the blood flow across
the tissue, even if upstream pressure seems adequate (C). The upstream pressure of the capillaries lies next to the arteriolar site of
vasoconstriction. Therefore, when arteriolar vasoconstriction is excessive, even if arterial pressure may be high, upstream pressure determining
the driving pressure across capillaries may be low, resulting in a decreased tissue blood flow.

contribute to organ dysfunction (venous conges-
tion), as in the cardio-renal syndrome, for example
(Figure 12.3C).14,15 Finally, even if the arterial pressure
seems adequate, increasing arteriolar vasoconstriction
induced by the use of vasopressors, for example, may
be responsible for significant perfusion pressure
loss (Figure 12.3D). Consequently, postarteriolar pres-
sure decreases, leading to a decrease in capillary perfu-
sion pressure, inducing tissue hypoperfusion. This
mechanism (peripheral resistance-induced macro-
microcirculatory decoupling) can be observed in the
distal limb of hypovolemic patients under high doses
of norepinephrine.
Preload and venous return
To improve SV, preload must be adequate. Excessive
preload, especially in cases of decreased ventricular
compliance, however, may be associated with the
high ventricular pressure responsible for pulmonary
and/or systemic congestion. Preload is defined as the
degree of tension of the cardiac muscle (stretching
of cardiomyocyte) before contraction. As this cannot
be measured directly, clinicians may estimate pre-
load either by volumetric indices or by ventricular
filling pressure measurements. Since volumetric
indices may be better related with the degree of
stretch of the myocardium than with pressure, pre-
load can be defined as the ventricular end-diastolic
volume.16
The volume–pressure relationship depends on
the compliance of the cavity. Any change in ven-
tricular compliance may change the measured pres-
sure for the same volume. Therefore, a preload state
may be the same for different measured pressures.
Moreover, measured pressures reflect intra-cavitary
pressures and not the physiologically relevant trans-
mural pressures (transmural pressure ¼ intra-
cavitary Pr –extra-mural Pr). As a result, no static
parameters (central venous pressure, pulmonary
artery occlusion pressure) allow accurate preload
estimations.
The preload has two roles: to provide enough
fluid to be ejected and to recruit the force of con-
traction through the Frank–Starling mechanism.

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Preload dependency Preload independency
Stroke volume
Preload (left ventricular end-diastolic volume)
Figure 12.4. Starling’s law of the heart. The relationship between
ventricular preload and stroke volume determines the heart function
curve. The heart function curve can be separated in to two zones,
depending on the effect of change in preload on the stroke volume.
In the preload-dependent zone, an increase in preload will result in a
significant increase in stroke volume and thus in cardiac output. In
the preload independent zone, a further increase in preload will no
longer result in a significant increase in stroke volume.
The Frank–Starling law of the heart states that, over
a specific range of preload, an increase in preload
will result in an increase in ejection volume defining
a situation of preload dependency (Figure 12.4).
Above a certain preload, the force of contraction
cannot be increased. Over this range of preload,
any increase in preload will be associated with an
increase in ventricular pressure, with no increase
in SV, defining a situation of preload independency.
In clinical practice, fluid infusion may improve the
hemodynamic state only if the specific function of
the heart is in a preload-dependent state. Otherwise,
fluid infusion will result in fluid overload. For the
left heart, fluid overload and associated high ven-
tricular pressure can induce a rise in pulmonary
capillary pressure, resulting in pulmonary edema.
The amplitude of the increase in pressure depends
on left ventricular compliance, therefore in a situ-
ation where the left ventricular (LV) compliance is
low, as in LV diastolic dysfunction (acute ischemia,
ventricular hypertrophy) a rise in LV end-diastolic
pressure could be significant. Therefore, with low
LV compliance, the optimal range of ventricular
volume is also narrow.
Ventricular preload is generated by the venous
return to the heart.17–19 The venous compartment
contains a large fraction of the total systemic
blood volume (70%). The part of this volume
that did not contribute to pressure generation is
called the unstressed blood volume (i.e., venous blood
volume at a venous transmural pressure near zero).
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Chapter 12: Critical care and anesthesia
Venous return
With
PEEP
0 Right atrial pressure
MSFP1 MSFP2
Figure 12.5. The relationship between venous return and right
atrial pressure (i.e., the downstream pressure or back pressure of
venous return) at different values of mean systemic filling pressure
(MSFP; representing the upstream pressure of venous return) and
venous resistance (VR). At a fixed MSFP, venous return increases
when the right atrial pressure decreases until a negative venous
transmural pressure results in a venous collapse, limiting a further
increase in the venous return. At a constant resistance to the venous
return (VR1), an increase in MSFP (MSFP1 to MSFP2) will result, at any
fixed value of right atrial pressure, in an increase in venous return. On
the other hand, at a fixed value of MSFP (MSFP1), a decrease in
venous resistance will result in a higher venous return for any fixed
value of right atrial pressure. Positive pressure ventilation with PEEP
will result in a right-ward shift in the venous return curve, limiting
the return of blood to the heart.
This volume keeps the venous system open, but with-
out pressure. Then, as the venous blood volume
increases, the venous pressure will increase and
determine the stressed blood volume (i.e., venous
blood volume above the unstressed blood volume that
is responsible for the generation of a positive venous
transmural pressure). Magder et al. suggested that the
stressed blood volume represents only a quarter of the
total blood volume, providing a large reserve of
unstressed blood volume.20 As soon as the stressed
blood volume generates a pressure above the down-
ward pressure (right atrial pressure), the positive
pressure gradient generates a flow: the venous return.
The venous return is thus determined by the
pressure difference (driving pressure of the venous
return) between upstream pressure (mean systemic
filling pressure: MSFP) and downstream pressure
(right atrial pressure [RAP]) and can be described
by the equation: Venous return ¼ (MSFP – RAP) /
Venous resistance (Figure 12.5). Venous return will
then increase if MSFP increases for a constant RAP
and venous resistance, or if RAP decreases with a
constant MSFP and venous resistance. However, if
RAP decreases under a critical pressure (close to the
99
 Section 2: Cardiovascular Physiology
extramural pressure), the transmural pressure
becomes negative, leading to the collapse of the vein,
limiting the flow of the venous return. This phenom-
enon of flow limitation may protect the heart
from excessive venous return (excessive ventricular
preload) when the patient generates very low pleural
pressure, for example, during high inspiratory effort.
As pressure and volume are linked by compliance,
MSFP pressure may increase as a consequence of
two interventions: an increase in volume, such as
during fluid expansion, for a constant venous compli-
ance, or by a decrease in venous compliance with a
constant volume, such as following venoconstriction.21
Fluid loading increases the stressed blood volume with-
out impacting on the unstressed blood volume, while
venoconstriction contributes unstressed blood toward
the stressed blood volume. At the bedside, clinicians
may thus increase venous return, and consequently
ventricular preload, by infusing fluid or by inducing
venoconstriction (phenylephrine, norepinephrine).
Fluid infusion may be more efficient, as the second
determinant of venous return, apart from the driving
pressure, is the venous resistance (Figure 12.5).
For any driving pressure, venous return decreases
when venous resistance increases. Fluid infusion
increases the diameter of the vein and thus reduces the
venous resistance, while the impact of venoconstriction
on venous resistance is difficult to predict (there are
different effects on large veins from those on venules).
Various situations may increase the venous resistance
to flow. For instance, an increased intra-abdominal
pressure (abdominal compartment syndrome, preg-
nancy) may limit venous return, despite an insufficient
increase in MSFP. This situation may result in a
preload-dependent decrease in cardiac output that
would not necessarily respond to fluid infusion or
venoconstriction, but that would dramatically improve
after freeing up the abdominal constraint (opening
the abdominal wall or draining the cavity).
Generation of the ventricular preload is mainly
determined by the diastolic phase of the heart cycle
(relaxation phase), and a normal heart filling is almost
completed at early diastole. However, in situations
characterized by an alteration of the relaxation phase
(diastolic failure), filling needs time, and occurs
during the entire diastole. Therefore, any factor that
would decrease the capacity of the ventricle to fill may
be associated with a limitation in preload generation.
This situation may occur when ventricular compli-
ance is decreased by intrinsic change of the ventricle
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(hypertrophic cardiomyopathy) or by extrinsic factors
(pericardial restriction, cardiac tamponade, or lung
hyperinflation). Duration of the diastole and the
contribution of the atrial contraction (30%–40% of
the filling) to ventricular filling may then limit gener-
ation of the preload.22
Assessment of the preload and especially the preload
dependency–independency state is difficult. The static
preload parameters (central venous pressure or pul-
monary artery occlusion pressure) that are influenced
by various physiological parameters (volume, compli-
ance, heart function, or extramural pressure), do not
allow adequate prediction of fluid responsiveness.23,24
The dynamic parameters (pulse pressure variation
[PPV] or stroke volume variation) are better indices as
they are based on the influence of cardiopulmonary
interactions, which are amplified in a state of preload
dependency (see heart–lung interactions).
Inotropy (contractility)
The second determinant of stroke volume, cardiac ino-
tropy, refers to the intrinsic ability of the myocardial
muscle to change its generation of force indepen-
dently of the preload. Inotropy can be described
in various terms: in terms of a length–tension relation-
ship (Frank–Starling curves: as an increase in tension
for a determined length [preload]); as the maximal
force generated at any ventricular volume (end-systolic
pressure–volume relationship); in terms of a force
(afterload)–velocity (of muscle shortening) relation-
ship; as an increase in velocity of shortening at zero
force (Vmax); or as an increase in the rate of pressure
generation that can be estimated by the ratio of pressure
change (dP) over a period of time (dt) : dP/dt.
With a constant value of preload and afterload, the
consequence of a variation in inotropy is a change in
stroke volume. When inotropy decreases, the Frank–
Starling curve is shifted downward and to the right,
resulting in decreased stroke volume, increased end-
diastolic volume, and increased end-diastolic pressure
(Figure 12.6). The amplitude of the increase in end-
diastolic pressure depends on the ventricular compli-
ance. In terms of preload, a decrease in inotropy may
thus transform a state of preload dependency into a
state of preload independency. Conversely, an
increase in inotropy will results in increased stroke
volume, decreased end-diastolic volume, and
decreased pressure. Usually, this change in preload
can be observed at the bedside after initiation of
 Chapter 12: Critical care and anesthesia

inhibition of intracellular cAMP corrosion by the

Normal inhibition of phosphodiesterase III (Milrinone), or by
an improvement in the efficiency of myofilament con-
Stroke volume

traction (calcium sensitizers). Although they allow an

1 Inotrope acute increase in the force of contraction, catechol-
Decreased
2
inotropy amines may also lead, in excess, to stress cardiomyop-
athy, resulting in a decrease in heart function. Increased
sensibility to circulating catecholamines at the apex
of the heart may explain the geometric characteristics
of takotsubo cardiomyopathy.27,28
Preload (left ventricular end-diastolic volume)

Figure 12.6. Relationship between ventricular preload and stroke Afterload

volume whatever the contractility. As ventricular contractility
(inotropy) decreases, the heart function curve is shifted right and
The afterload is the tension developed by the ventricle
downwards (1 to 2) resulting in a decrease in stroke volume and an during ejection and can be considered as the load
increase in left ventricular end-diastolic volume. Inotropic drugs may (impedance in a pulsatile system) against which the
improve stoke volume, while decreasing left ventricular end-diastolic
volume and thus ventricular pressure as the heart function curve
heart must contract in order to open the aortic valve
returns toward the baseline. and promote forward flow (blood ejection). The end-
systolic ventricular pressure defines this parameter.16
Afterload can be described, according to Laplace’s
inotropes that induces a decrease in central venous
law, as the repeated instantaneous wall stress of the
pressure or pulmonary artery occlusion pressure. The
ventricles, ventricular wall stress being wall tension
present paradigm explains why a fixed static value of
(ventricular pressure × ventricular radius, during
central venous pressure or pulmonary artery occlu-
ejection) divided by wall thickness. Thus, afterload
sion pressure is not able to accurately estimate fluid
integrates various parameters: ventricular structure,
responsiveness.
ventricular function, impedance, and resistance to
Myocardial contraction is related to actin–myosin
the ejection. This last component, when aortic or
interaction, facilitated by calcium (Ca2+) binding to
pulmonary valve or outflow tract are normal, is
troponin C and ATP. To maintain or improve
mainly determined by the characteristics of the
inotropy, first, oxygen delivery must be adapted to
arteries (systemic or pulmonary arterial load). To
the cellular needs. Unlike other organs, the myocar-
maintain the same ejection, an increase in afterload
dium has a low reserve of oxygen extraction that can
will be associated with an increase in the myocardial
compensate for a decrease in oxygen supply. (Oxygen
work. If the ventricle is unable to generate enough
extraction of the left ventricular myocardium is close
work, the volume of ejection will decrease, resulting
to 75% at rest.) The myocardium must thus depend on
in a reduction of the cardiac output and an increase
an increase in coronary blood flow to meet increased
in ventricular volume (Figure 12.7).
metabolic demand. Coronary perfusion must then
Afterload must then be maintained as low as
be maintained and the coronary flow reserve (the
possible, especially in situations with a decreased
difference between resting and maximal coronary
contractility and for the right ventricle. However, a
blood flow) must be adequate, otherwise the force of
certain amount of aortic pressure is mandatory for
contraction may be limited. If hypoxia persists, cellular
maintaining coronary perfusion and the driving
ischemia will ensue, inducing transitory or definitive
pressure of organ perfusion. Therefore, in cases where
loss of cardiac cells and myocardial function.25,26
an afterload value cannot be tolerated, mechanical
Before stimulating the myocardium with inotropes,
assistance (intra-aortic balloon counterpulsation, ven-
it is therefore essential that the coronary flow reserve
tricular assistance, etc. . .) may be required.
can meet the increased demand in oxygen by the
myocardium. Once myocardial oxygen delivery has
been confirmed, inotropic stimulation may be used. Specificity of the right ventricle
Inotropes increase contractility by different pathways: The right ventricle (RV) differs from the left ventricle
by stimulation of beta-adrenergic receptors – subtype 1 (LV) in various ways and can be considered to be a
(dopamine, dobutamine, isoprenaline, adrenalin), high-volume-low-pressure pump (volume primed but

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 Section 2: Cardiovascular Physiology
Right ventricle Left ventricle
Stroke volume
Normal
Decreased
inotropy
Afterload
Figure 12.7. Influence of afterload on right- and left-ventricular
stroke volume. On the left side of the heart, the stroke volume
of a normal left ventricle is influenced only at high afterload, as
ventricular work reserve is high. However, at decreased left
ventricular contractility (decreased inotropy), stroke work reserve
may not allow compensation for an increase in afterload and may
result in a decrease in stroke volume. Unlike the left ventricle,
due to anatomical structural and geometrical factors the right
ventricle does not tolerate any further increases in afterload.
pressure unprepared). The RV is thinner (one-sixth of
the LV), decreasing its capacity of force generation.
Its geometry is crescent-shaped, lying on the LV and
it contracts inward, longitudinally, and by traction
on the free wall, resulting in greater longitudinal than
radial shortening. As the RV lies on, and is bound
to, the LV through the septum, its contractility is
partly generated by the LV.29 Unlike the LV, the RV
is highly sensitive to afterload, relying on preload and
force of contraction (Figure 12.7). Moreover, the RV
is excessively preload sensitive allowing it to recruit
a force of contraction through the Frank–Starling
mechanism. However, volume overload of the RV
may result in right–left ventricular interaction,
impairing left ventricular diastolic function.30,31
Heart–lung interactions
It is essential to understand heart–lung interactions in
order to understand hemodynamic interactions in
patients under mechanical ventilation and during the
assessment of dynamic parameters of preload.32,33
Influence of static heart–lung interactions
on preload
A stable increase in intrathoracic pressure (PEEP) has
multiple influences. First, pressure may be transmit-
ted to the right atrium, resulting in a decrease in
the pressure gradient of venous return. Second, the
influence of intrathoracic pressure on venous return
may be amplified through an increase in venous
102
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resistance.34 Both of these effects result in a decrease
in venous return, ventricular preload, and thus right
ventricular stroke volume,32,35 but can be limited
by a simultaneous increase in mean systemic filling
pressure (the input pressure of the venous return),
maintaining the venous return. This adaptation to
increased intrathoracic pressure (PEEP) is mediated
through neurohumoral36 and mechanical factors,37
but may be blunted during hypovolemia. This
explains why PEEP may induce a significant decrease
in cardiac output in hypovolemic patients that
generally improves after fluid replacement. It must
be noted that severe lung inflation may induce a
progressive compression of the heart, resulting in a
restriction of ventricular diastolic filling.38
Influence of static heart–lung interactions
on afterload
During the inspiration phase of positive pressure
ventilation, the aortic transmural pressure decreases
(increase in pleural pressure), reducing the left ven-
tricular afterload and favoring ejection. This effect
can be especially beneficial in the presence of left
ventricular heart failure. Conversely, during spontan-
eous respiration, the decrease in pleural pressure will
result in an increase in left ventricular afterload
(increase in aortic transmural pressure), imposing a
greater load on the LV.
The effect of heart–lung interaction on the right
ventricle is different. As the lung volume increases
above its functional residual capacity, in spontaneous
or positive pressure ventilation, the pulmonary
arterial resistance increases due to the compression
of the vascular bed (capillaries) by the expanding lung
(increase in lung West zones I and II at the expense
of zone III).39
Cyclic influence of mechanical ventilation
on the hemodynamic state
First, as already stated, on the right side, a positive
intrathoracic pressure is responsible for an increase
in right atrial pressure and an increase in venous resist-
ance to the venous flow, resulting in a decrease in
venous return. Second, as the expanding lung
volume increases the right ventricular afterload, right
ventricular ejection decreases, resulting in a decrease in
transpulmonary blood flow. This limits the left ven-
tricular preload, which may decrease further in the case

of right ventricular volume or pressure overload (septal
shift to the left compresses the LV and limits its diastolic
expansion, decreasing LV compliance). After a few
heartbeats, corresponding to the pulmonary vascular
transit time, the left ventricular preload decreases,
with a concomitant decrease in LV stroke volume.
The relative increase in venous return on the right
side during expiration results in an increase in left
ventricular preload and SV a few heartbeats later,
during the mechanical breath. Moreover, at inspiration,
the increase in transpulmonary pressure (Palv > Ppl)
expands lung volume and may “squeeze” the capillaries,
recruiting lung blood and resulting in an early and
transitory increase in the left ventricular preload.40
At the same time, due to the increase in pleural pres-
sure, the left ventricular afterload decreases, resulting
in an increase in LV stroke volume.
Various factors may affect these heart–lung
interactions during positive pressure ventilation. In
hypovolemia, resulting in a state of preload depend-
ency, the amplitude of the variation of left ventricular
ejection increases with ventilation. When there is
spontaneous respiration during positive pressure
ventilation, as pleural pressure and alveolar pressure
are influenced by movable respiratory rate and
spontaneous effort, cardiopulmonary interactions
described may be unpredictable. The tidal volume
also influences the importance of cardiopulmonary
interaction, particularly because of the influence of
lung volume on transpulmonary pressure.
Cardiopulmonary interactions may be used to
treat patients. For example, the physiological man-
agement of pulmonary edema is determined by
the relation between the left ventricular volume and
compliance. An elevated left ventricular pressure
induces a postcapillary pulmonary vascular hyper-
tension responsible for initial interstitial edema.
Left ventricular pressure rises as ventricular
volume increases and/or as ventricular compliance
decreases. Therefore, in clinical practice, the treat-
ment of pulmonary edema consists of reducing
ventricular pressure essentially by a decrease in the
end-diastolic volume (preload). This can be achieved
by decreasing venous return through increasing
venous compliance with venodilatators, a decrease
in blood volume (diuretics), or by positive pressure
ventilation (decreasing venous return to the LV).
Moreover, the left ventricular volume can be
decreased by increasing left ventricular ejection
through decreasing afterload.41
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Chapter 12: Critical care and anesthesia
Considering the weaning of positive pressure
ventilation, two factors therefore seem important:
heart function must be recovered and fluid overload
avoided. Positive pressure ventilation decreases the
oxygen requirement from the respiratory muscles
and supports the heart, assisting systolic function
and limiting venous return. Thus weaning failure
may be due to the inability of the hemodynamic
system to support the new physiology and maintain
oxygen supply to the organs. First, heart function
must have recovered sufficiently to support the
decreased assistance of the LV by positive intrathor-
acic pressure. An apparent imbalance DO2/VO2
during weaning, representing an inability of the heart
to ensure the increased oxygen demand, can be
assessed by various means, for example, by the trend
of central venous blood saturation.42 Second, as
positive pressure limits the venous return and thus
protects the heart (Figure 12.5), any excess circulating
blood volume must be avoided before weaning of
positive pressure ventilation. An increase in ventricu-
lar pressure (pulmonary artery occlusion pressure,
for example) during weaning may indicate an inad-
equacy between the increase in venous return and
the heart function.43
Dynamic cardiopulmonary interactions may
also be used to determine the physiologic state
of the hemodynamic system. Dynamic indices of
preload, used to predict a state of preload depend-
ency, originate from these interactions. Among the
dynamic indices, pulse pressure variation is widely
used (Figure 12.8). The origin of pulse pressure
variation is related to cyclic perturbation of the car-
diovascular system by the respiratory system. The
perturbator (respiratory system) increases or
decreases the LV volume of ejection as discussed
previously. However, to be clinically relevant, the
present perturbation must be sufficient (enough
tidal volume [> 6 mL/kg], stable chest compliance,
stable transmission of pressure), unperturbed with
constant respiratory cycles (no spontaneous respir-
ation), and a stable cardiovascular system (regular
cardiac rhythm).
From macrocirculation to
microcirculation
Microcirculation is the “vital” part of the cardiovas-
cular system, consisting of a network of small vessels
(5–200 μm) including arterioles, capillaries, and
103
 Section 2: Cardiovascular Physiology

Expiration Inspiration Expiratory pause

∆Up
SPVI
Arterial pressure

∆Down

PPmax

PPmin

PPref
time
Pulmonary transit time Pulmonary transit time

End-inspiration End-expiration
(Positive pressure (Positive pressure
ventilation) ventilation)

Figure 12.8. Arterial pressure variations during positive pressure ventilation without spontaneous effort. Due to cardiopulmonary
interactions, inspiration induces a decrease in right ventricular stroke volume, due to a decrease in venous return and an increase in right
ventricular afterload. After a few heart beats (pulmonary transit time), the present decrease affects the left ventricular filling and stroke volume.
The pulse pressure (PP) represents the difference between systolic and diastolic arterial pressure. Pulse pressure is maximal (PPmax) a few
heart beats after the end of expiration and lower (PPmin) a few heart beats after inspiration. The difference between maximal and minimal
pulse pressure determines the pulse pressure variation (PPv). The difference between maximal and minimal systolic pressure define the
systolic pressure variation (SPV) that comprises two values (∆Up and ∆Down), according to the reference value of systolic arterial pressure
(PPref) obtained after an expiratory pause.

venules.11 Its function resides in the regulation of macrocirculatory pressure, but it may also be associ-
exchanges between blood flow and tissue. Therefore, ated with a paradoxical reduction in the capillary
its anatomical and functional integrity is essential bed perfusion pressure, due to the loss of pressure in
to assure cellular oxygenation. the highly resistant arteriolar vascular network.44
Microcirculatory perfusion is determined by
macrocirculatory parameters (arterial blood pressure,
viscosity, DO2) and by specific microcirculatory Conclusions
parameters. In various situations, microcirculatory In summary, the key to treating the changes that
perfusion may be decoupled from macrocirculatory occur in a patient’s cardiovascular status is under-
parameters. During septic shock, for example, tissue standing the underlying physiology and how this
hypoperfusion may persist, despite normal macro- has been disturbed. When applied to anesthesia and
circulatory parameters. Consequently, in some cases, critical care, cardiovascular physiology provides
commonly measured macrocirulatory parameters paradigms and knowledge that could be used to
may not allow prediction of tissue perfusion. Various treat patients and to improve their critical state on a
mechanisms contribute to changes in microvascular daily basis. Recently, great progress was made in
perfusion: perfusion pressure, rheological factors, and perioperative hemodynamic monitoring and goal
alteration of the microcirculation autoregulation. directed therapy for these kinds of patients, with a
Considering capillary perfusion pressure, the input primary focus on concepts and algorithms able to
pressure of the capillary bed resides in the vascular assess cardiovascular integration and tissue resusci-
pressure next to the arteriole, which is the main site tation. At the beginning of the new millennium, this
of vasoconstriction and resistance (capillaries are evolution is an important indicator, highlighting
devoid of muscular tissue). Therefore, an increased the major shift of hemodynamic monitoring toward
arteriolar vasoconstriction results in an increase in a pragmatic approach.

104
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