Angina (Concepts)

Question 1

What is angina pectoris?

Answer 1

Condition describing chest pain (and referred over left shoulders and upper arm) due to inadequate blood supply to the myocardium.

Question 2

Why does sympathetic stimulation reduce oxygenation of the myocardium?

Answer 2

1. Increased heart rate, reducing duration of diastole and thus duration of myocardial perfusion.
2. Increased force of contraction and work done by myocardium thus increasing O₂ demand.
3. Decreased efficiency of myocardium so that more O₂ is used for same amount of work done.

Question 3

Why does sympathetic stimulation cause angina in individuals with atherosclerosis but not healthy individuals?

Answer 3

1. In healthy individuals, increased O₂ demand to the myocardium during sympathetic stimulation is met by arteriolar vasodilation.
2. Atherosclerosis causes narrowing of coronary arteries so that arterioles are dilated normally to maintain adequate cardiac perfusion.
3. During sympathetic stimulation, there is no extra capacity for increased blood supply by arteriolar vasodilation.
4. Myocardium becomes ischaemic and causes angina.

Question 4

What changes in the myocardium occur in patients suffering from long-term angina?

Answer 4

Collateral vessels develop in coronary circulation and reduce the effects of ischaemia.

Question 5

What causes variant angina?

Answer 5

Coronary arterial spasms (unknown cause)

Question 6

What are the principles by which anti-anginal drugs function?

Answer 6

1. Increase perfusion of myocardium
2. Reduce O₂ demand of myocardium

Question 7

What is the mechanism of action of nitrovasodilators in treating angina?

Answer 7

Organic nitrates act as substrates for eNOS, increasing production of NO, which has 3 effects:

1. Vasodilation of coronary arteries/arterioles, increasing perfusion of myocardium.
2. Dilation of larger muscular arteries reduces pulse wave reflection, thus reducing afterload. This reduces workload and O₂ consumption of the heart.
3. Dilation of veins reduce MSFP, reducing CVP, VR and thus preload. This reduces workload and O₂ consumption of the heart.

Question 8

What is the fortuitous function of nitrovasodilators in terms of dilaton of coronary vessels?

Answer 8

• They cause vasodilation of select collateral vessels in heart instead of general vasodilation of all vessels.
• This allows blood to be diverted from less well perfused areas to better perfused areas.
• General vasodilation would cause ‘coronary steal’ whereby blood is diverted away from less well perfused areas due to high resistance of narrowed vessels.

Question 9

What are the side effects of nitrovasodilators?

Answer 9

1. Headaches: Vasodilation of cerebral vasculature
2. Postural hypotension: Vasodilation of systemic vasculature

Question 10

What is the consequence of prolonged nitrovasodilator use?

Answer 10

Development of tolerance possibly as a result of depletion of -SH groups in body, which is required for their function.

Question 11

What is the mechanism of action of β-blockers in treating angina?

Answer 11

Reverses effects of sympathetic stimulation of increasing myocardium O₂ demand.

Question 12

What is the mechanism of action of I_f blockers in treating angina?

Answer 12

Inhibition of I_f reduces heart rate which has 2 effects:

1. Increases time spent in diastole and thus perfusion
2. Decrease the work of the myocardium

Question 13

What type of Ca_v antagonists are used to treat angina and why?

Answer 13

• Dihydropyridines
• More selective for Ca_vs in VSM

Question 14

What is the mechanism of action of Ca_v antagonists in treating angina?

Answer 14

1. Vasodilation in coronary vessels: Increases perfusion of the heart
2. Vasodilation of systemic vessels: Decreases afterload and thus work of heart

Question 15

What are the contributions of the late Na⁺ current to angina?

Answer 15

• Late Na⁺ current in cardiac myocytes increases intracellular [Na⁺] which decreases efficiency of NCX.
• Causes increase in intracellular [Ca²⁺], which decreases the rate of relaxation of myocardium, increasing ventricular wall stiffness and end-diastolic pressure.
• This causes increased compression of coronary vasculature, impairing perfusion of myocardium during diastole.

Question 16

What is ischaemic pre-conditioning?

Answer 16

Phenomenon whereby short periods of ischaemia protects the heart against ischaemic reperfusion injury.

Question 17

What are the mechanisms of action of K_ATP antagonists in preventing ischaemic reperfusion injury?

Answer 17

1. Opening of mitoK_ATP channels may decrease the rate of ATP depletion within the mitochondria (possibly as a result of reduced ATP synthase activity that reverses in stoichiometry during ischaemia and causes ATP hydrolysis instead).
2. Nicorandil may also act as NO donor and aid in NO-dependent ischaemic pre-conditioning.
3. It may also open K_ATP channels in VSM cells, causing hyperpolarisation and relaxation. This leads to vasodilation and improved perfusion of myocardium.

Question 18

What are the surgical treatments for ischaemic heart disease?

Answer 18

1. Coronary artery bypass grafting (CABG)
2. Percutaneous coronary intervention (PCI)

Question 19

What are the problems with coronary angioplasty with insertion of stent?

Answer 19

Development of scar tissue around stent (neointimal proliferation) causing further narrowing of vessel.

Question 20

How is neointimal proliferation prevented after angioplasty?

Answer 20

Use of drug-eluting stents that inhibit cell growth