CTSN - Cardiovascular Physiology/Pharmacology

Cardiovascular Physiology/Pharmacology

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1. Heart Muscle Mechanics - 3 concepts

(1) TENSION (force) - Elements contributing:

Contractile element => Active tension

Elastic element (functional, not anatomic) => Resting tension

(2) LENGTH of muscle fibers influences Tension

Starling's relationship (Tension (active & resting) vs Length)

Performance-wise this is PRELOAD effect

(3) VELOCITY is influenced by Length and Tension

Calcium activation

Total calcium released

Sarcomere length alters calcium sensitivity

2. Cardiac Performance Cardiac output = HR x Stroke volume

Stroke Volume affected by

Preload

After load

Contractility
Law of La Place relates ventricular pressure and wall tension

T = Pr

3. The cardiac cycle
Isovolumetric ventricular contraction

Rapid ejection phase

Reduced ejection phase
Isovolumetric relaxation

Rapid filling phase

Slow filling period

(Atrial contribution (20-30% in failing heart))

4. Preload
Normal heart - increased venous return results in increased cardiac output
Failing heart - sarcomere length is already maximal; cardiac output increase requires increased contractility or heart rate
After load
Definition
Increased after load - increase in LVEDV and radius (=preload)
Anrep effect or homeometric autoregulation
Contractility - inotropic state of muscle

5. Indicators of Cardiac performance
Cardiac index = cardiac output/body surface area

LVEDP (or approximation)

mean left atrial pressure

mean pulmonary wedge pressure

pulmonary artery diastolic pressure
CI and LVEDP together are better indicators of contractility than either alone
Ejection fraction = stroke volume/end-diastolic volume
Fractional shortening - calculated from the diameter perpendicular to the midpoint of LV long axis

6. Coronary flow & myocardial O2 consumption
Very efficient oxygen extraction (70% oxygen utilization coefficient)
Coronary hemodynamics - Q = P/R
Viscous resistance
Autoregulatory resistance
Compressive resistance
Transmural gradient in myocardium - DPTI x HR = driving pressure
Myocardial oxygen consumption
Pressure work, contractility, heart rate, basal cell metabolism, electrical activation

CARDIOVASCULAR PHARMACOLOGY 7. Inotropes

Digitalis

Inhibit Na-K-ATPase - positive inotropic effect

Parasympathomimetic and anti-adrenergic mechanisms

Drug interaction - Quinidine, Verapamil, Amiodarone

Conditions that increase sensitivity

8. Inotropes, Vasoconstricting

Dopamine

Low doses - D1 receptors in renal vasculature

Increasing doses - b-1 receptors activated

High doses - a-adrenergic receptor activation

Epinephrine

Potent b and a effects

Norepinephrine

Potent alpha effects

9. Inotropes, Vasodilating

Dobutamine

Beta > alpha effect

Reduces LV filling pressures

Decreases afterload

Milrinone, Amrinone

Phosphodiesterase inhibitors

Isoproterenol

Inotropic (beta), chronotropic effects

10. Vasodilators & Vasoconstrictors

Vasodilators

Nitroprusside

Generalized vasodilatation

" Steal phenomena"

Indications - hypertension, acute heart failure

(thiocyanate toxicity - rare; with renal failure)

Nitroglycerine

General vasodilatation

Low doses - venous; high doses - arterial

Preload reduction and coronary vasodilation

Useful in management of ischemia

Decrease LVEDP and pulmonary vascular congestion

NO and Isoproterenol - pulmonary effects

Vasoconstrictors

Neosynephrine (pure alpha)

11. Calcium Antagonists

Mechanisms

Interference of Ca2+ - mediated smooth muscle contraction - coronary and peripheral smooth muscle relaxation

Selective Ca2+ channel inhibition

Treatment of angina pectoris / supraventricular tachycardia / hypertension

Agents

Verapamil

Nifedipine

Diltiazem

12. ACE Inhibitors

Mechanisms

Prevent conversion of Angiotensin I to Angiotensin II - vasodilation

Decreased Aldosterone secretion

Indication - hypertension, heart failure, prophylactically after MI

Agents

Captopril

Low cardiac output states - improvement in renal blood flow

Angioedema/cough/neutropenia/nephrotic syndrome

Increase in creatinine - RAS

Enalapril

Enalaprilat (liver) - delay - long duration

Less side-effects

13. Beta Blockers

Mechanisms

b-1 and b-2; cardioselectivity

Indications

Hypertension, angina pectoris, arrhythmias, prophylactically after MI

Adverse effects

Bronchospasm, Inhibition of myocardial contractility

Drug interactions

Lidocaine/Verapamil/Cimetidine/Diltiazem

Agents

Propanolol, metropolol, atenolol

Esmolol - very short half-life

14. Anti-arrhythmic Drugs and Their Actions

Class	Action	Agents
IA	Inhibit Na+ transport	Quinidine
	Reduced dV/dT of action potential	Procainamide
IB	Slow dV/dT of phase 0	Disoprymadine
	Moderate prolongation of repolarization	Lidocaine
	Prolongs PR, QRS, and QT intervals	Phenytoin
	Limited effect on dV/dT of phase O	Mexiletine
	Shortens repolarization	Tocainide
	Shortens QT in clinical doses
	Elevates fibrillation threshold

15. Anti-arrhythmic Drugs and Their Actions

Class	Action	Agents
IC	Markedly slows dV/dT	Flecainide
	Little effect on repolarization	Ecainide
	Markedly prolongs PR and QRS
II	Beta-adrenergic blockers	Metoprolol
	Decrease nodal conduction	Atenolol
		Propanolol
III	Prolongs repolarization	Amiodarone
	Alters membrane response	Bretylium
IV	Calcium channel blockers	Verapamil
	Decrease nodal conduction	Nifedipine
		Diltiazem

16. Thrombolytic Agents
Streptokinase - Indirectly activate plasminogen to plasmin => fibrin into FDP's (non-specific)
Urokinase - Indirectly - thrombolysis (non-specific)
tPA (Alteplase) - Clot specific thrombolytic - binds directly to clot via fibrin
APSAC - Like Streptokinase