Pharmacology of Cardiovascular Physiology

Question 1

Outline what cardiac glycosides do?

Answer 1

Cardiac glycosides such as digoxin
. modulate contractility pharmacologically
. increase the force of contraction -
.Mechanism of Action = inhibit the Na+/K+ ATPase, so Na+ cannot be extruded from the cell
. Therefore intracellular Na+ increases and inhibits the NCX so Ca2+ is not extruded from the cell and accumulates - meaning more Ca2+ is available for contraction
. In short, cardiac output increases because SV (ionotropy) increases

Question 2

What affect do cardiac glycosides have on cardiac ouput.

Answer 2

. Increase cardiac output
Increase Stroke Volume -
enhanced contractility = inotropy
+ Slow heart rate by enhancing vagal tone -> leads to slowing of SAN and AVN conduction and thereby a reduction in heart rate
Pharmacological application - slow heart rate + more powerful contraction + improved filling of ventricles = can be used for treating atrial fibrillation after other options like beta blockers and calcium channel blockers do not work

Question 3

Give the equation for cardiac output

Answer 3

Cardiac output = stroke volume times heart rate

Question 4

Heart is modulated excessively by the autonomic nervous system
Stroke volume = subject to both intrinsic and extrinsic control - state what the intrinsic and extrinsic control are?

Answer 4

Intrinsic = change in fibre length
Extrinsic = modulation in contractility

Question 5

Experimental evidence for Frank-Starling Mechanism - Frank part

Answer 5

Frank - using isolated frog hearts
. strength of ventricular contraction was increased when the ventricle was stretched prior to contraction
. Frank - isolated & perfused frog hearts, then he measure ventricular pressure whilst injecting blood through dissected vena cava and found that an increased volume = increases the pressure generated

Question 6

Experimental evidence for Frank-Starling Mechanism - Starling part

Answer 6

. Starlings work supported the findings of Frank
- Starling’s work =
. increasing the venous return to the heart led to increased stroke volume
. decreasing venous return led to decreased stroke volume
- Starling demonstrated this experimentally on anaesthetised dog, increasing the preload by lifting the reservoir of blood to higher levels, using gravity to increase pressure

Question 7

Extrinsic Control