January 31, 2013

Dr. Bowie

PHAR 301
Lecture 8: Complications of Heart Disease

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Complications of heart disease

Arrhythmias, Diabetes, Embolism

Heart Structure & the Cardiac Cycle

Four chambered organ
Right ventricle expulses blood towards the
lungs to get oxygenated
Left ventricle (much bigger) pumps blood
to the systemic circulation
During atrial systole there is ventricular
diastole (Figure 1)
During ventricular systole there is atrial
relaxation
:ca
Arterial pressure (i.e in the aorta) changes
quite significantly in the cardiac cycle
Atrial pressure also changes, but not as
much
One cardiac cycle = atria contract,
Semilunar valve
ventricles contract (blood pushed out),
closure
Figure 1: The cardiac cycle
relaxation
o The right atrium is innervated first
How does the blood move?
o Blood pressure in the atria is slightly higher than the pressure in the ventricles (before
contraction)
Causes blood to go straight into the ventricles even as atria is filling up
Atr ial contraction is the fin al 'squeeze' of blood to fill the ventricles
The contraction of the atria is caused by a wave of depolarization
Pressure in the arteries is still higher than in the ventricles when the AV valves close
Pr eload is the pressure from the veins
o If this pressure is higher, the ventricles have to work more to close the valves (i .e.
hypertension)
Afterload is the pressure from to arteries
o If thi s is higher, the ventricles again have to work harder to open the valves (i.e.
hypertension)
The aorta "absorbs" the blood, and then contracts again
o While thi s occurs, the ventricular and arterial pressure have to be almost the same, to
prevent backflow

PHAR 301
Lecture 8: Complications of Heart Disease

o Once blood is pumped out the

semilunar valves close

Diastole: everything is relaxed, because it
is trying to go back to the homeostatic
situation at the start of the cardiac cycle

January 31, 2013

Dr. Bowie
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OAS complex
Cardiac Electrophysiology
STsegcnent
ECG wave (Figure 2):
o P wave = atrial depolarization
T.wave
P wave
o QRS complex = ventricular
depolarization
Atrial repolarization occurs
simultaneously but is
masked by the QRS
complex
o T wave= ventricular repolarization
o PR interval is the delay at the AV
Node
PR in terval
o SA Node: cells that initiate atrial
systole
Figure 2: Components of an ECG
o AV Node
Provides a delay in impulse transmission
Protects ventricles from atrial fibrillation
Bundle of His:
o Divides the L and R bundles
o Provides orderly and equally spread depolarization of the ventricles
If you record action potentials from different types of cells, values will be different
o Different cells use different ion channels
Na+
channels

o Must be a rapid depolarization

o Causes the upstream of the action potential
o Na+ channels switch off immediately after activation
o Na+ channels are considered the ignition
Ca2+ channels
o Activate more slowly, but remain open for a much longer period of time
o Are responsible for the actual contraction you see
o Plateau for a while before K+ and er channels activate
K\
Cr channels

o Responsible for repolarizing the membrane

o Why do these kick in later on? What explains the K+ and Cr ions coming in after the Ca2+
plateau?
K+ channels open much slower than Ca2+ channels
By the time the K+ channels allow the K+ ions to flow out of the cell, the Ca2+
channels have switched off

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PHAR 301
Lecture 8: Complications of Heart Disease

January 31, 2013

Dr. Bowie

K+ channels do not switch off as fast, K+ keeps exiting the cell, resulting in a
slight hyperpolarization of the membrane
Timing is everything
All 3 (Na+, Ca2+, K) channels are designed to have an inactive state

Cardiac Arrhythmias: Etiology

2 main causes
o Abnormal pacemaker activity
o Abnormal cardiac conduction
o Orboth
Ea~y atterdepalarizatian
Risk Factors
(arises from the plateau)
Prolonged
plateau
o lschemia, hypoxia,
Early
acidosis/alkalosis,
Af terdepolari zation
electrolyte
(Oft e n occur ot slow heart rate)
abnormalities (i.e. due
to diuretics)
o Excessive
catecholamine
exposure, autonomic
Delayed aflerdepalarization
influences (stress,
(arises from the resting
Delayed
goiters and excess
potential)
Afterdepolarization
thyroxine cause heart
(occur at fast heart rates)
rate to increase)
o Drug toxicity,
scarred/diseased tissue
possibly from a previous
Figure 3: Abnormal Pacemaker activity
heart attack
Treatment
o Electrical Devices (pacemakers, defibrillators)
o E lectrical ablation of abnormal pathways
o Drug treatment
Impulse Formation
3 ways of slowing normal pacemaker activity
o More negative diastolic potential (open K+ channels)
o Reduction of diastolic depolarization (block Na+ or Ca2 + channels)
o More positive threshold potential (shift voltage sensitivity of ion channels)
Abnormal Pacemaker Activity (Figure 3)
Early afterdepolarization
o Prolonged plateau causes an ectopic heart beat
o More likely when you are lying down since your heart is slowing down
Delayed afterpolarization
o Calcium overload caused by the Ca2+ channels that have not inactivated
o Too much contraction
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PHAR 301
Lecture 8: Complications of Heart Disease

January 31, 2013

Dr. Bowie

Disturbance of Cardiac Conduction

Normal conduction
o Action potentials going in opposite directions will eventually meet up with each other
o But already excited tissue cannot get excited again right away (kills the conduction)
A refractory period exists
~30 ms of inactivation
Prevents regurgitated excitation; what happens during ventricular fibrillation
Re-entry circuit
Some tissue is damaged and it can't be excited so there is a delay in the
extinguishing of the conduction. Conduction goes around and around the damaged
tissue.
Beginning of ventricular fibrillation
Common disturbance of conduction

Pharmacological Intervention
Anti-arrhythmic drugs (5 groups):
o Class 1: Na+ channel blockers (quinidine)
IA: slow intraventricular conduction (increase QRS) and increase ventricular AP
(increase QT)
lB: selective for abnormal tissue
1C: slow intraventricular conduction only
o Class 2: P-blockers (Propanolol)
Slow AV conduction and prolong the PR interval
o Class 3: IKr blockers (Sotalol)
Prolong ventricular AP therefore prolong the PR interval
o Class 4: L-type Ca2+ channel blockers (Verapamil)
Slow AV conduction and prolong the PR interval
o Class 5: Miscellaneous (including adenosine, K, Mg ions)
Anti-arrhythmic drugs have a very low therapeutic index and can provoke arrhythmias and heart
failure
Drug choice is always on a case by case basis, and often it is trial and enor to find the right drug

Diabetes

Type 1: Juvenile onset/ insulin dependent diabetes ( 10% total cases)

o Results from the body's failure to produce insulin, and presently requires the person to
inject insulin
Type 2: Insulin resistant/adult onset diabetes (80-90% of cases)
o Condition in which cells fail to use insulin properly, sometimes combined with an absolute
insulin deficiency
Body's cells are insensitive to insulin
Other Types
o Gestational (during pregnancy), congenital, cystic fibrosis related, steroid induced,
monogenic forms of diabetes
Diabetic macrovascular disease

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PHAR 301
Lecture 8: Complications of Heart Disease

January 31, 2013

Dr. Bowie

o Accelerated atherosclerosis involving the aorta, large and medium arteries

o Most common consequences: heart attack, gangrene of lower extremities
o Impaired circulation, tissue fragility of the limbs and feet, poor healing
Problems worsened by ischemic neuropathy
Hyaline arteriosclerosis
o Vascular lesion associated with hypertension
o Thickening of the wall of the arterioles with narrowing of the lumen
o More severe in diabetics
Diabetic microangiopathy
o Diffuse thickening of basement membrane
Most evident in capillaries of skin, skeletal muscle, retina, renal glomeruli/medulla
Diabetic capillaries are leakier to plasma proteins
Leads to development of diabetic nephropathy, some neuropathy
Side effects of some cardio drugs include hyperglycemia and diabetes
o Cardiovascular drugs, corticosteroids, atypical antipsychotics can induce or aggravate
hyperglycemia
o Cardiovascular drugs can inhibit insulin secretion
Clonidine (directly) and Ca2+ channel blockers (directly), or diuretics that deplete
K+ (indirectly)
Embolism
Arterial Emboli sm
o Source: Dilated left atrium in mitral stenosis (valve does not open completely), left
ventricle after heart attack, diseased abdominal aorta
o Consequence: May lodge in femoral artery and cause sudden critical ischemia of the
lower limb or in a branch of the Circle of Willis in the brain causing a stroke
Venous Embolism
o Source: Usually the deep veins of calf or thigh, but also the peri-prostatic venous plexus or
pelvic veins
o Consequence: Block of pulmonary trunk or major pulmonary arteries
This can cause a heart attack because it feeds back the blood pressure from the
lungs to the heart
Amniotic fluid embolism
o Infusion of amniotic fluid into the maternal circulation during pregnancy causing
shock/pulmonary problems
Air/gas embolism and fat embolism
Case Study
78 year old woman with a fractured hip
3 days post op: cough, chest and dyspnea (hard to inhale)
Friction rub at the right lung base; leathery sound caused by pleural membranes rubbing together
Long term immobilization can cause clot formation in the extremities
Deep vein thrombosis in thigh of injured leg
Nature of the surgery is also a huge risk factor
Complication: Poor circulation due to immobility caused a clot in the injured leg
o Resulted in pulmonary embolus
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PHAR 301
Lecture 8: Complications of Heart Disease

January 31, 2013

Dr. Bowie

To prevent: Give an anticoagulant (prophylactic heparin)

o Or a compression stocking, machine that decompresses knees, moves you around restoring
circulation. Have the surgery performed immediately after arriving at hospital.
Patient was started on heparin
o How does it act?
Inhibits thrombin formation
Inhibits binding to coagulation factors
o What kind should be used?
High molecular weight heparin (more effective but must be monitored) first but
lower version for longer term therapy
Summary
Why are cardiovascular diseases so important?
o Linked to other very prevalent diseases
What you need to know?
o Know the ANS, receptor types, neurotransmitters and where they act
o Remember how to control blood pressure (4 targets)
Resistance (arterioles)
Capacitance (venules)
Pump Output (hea11)
Volume (kidneys)
o Grasp the big picture of diseased states and how they are treated
Have to consider all problems

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