L2 (PA) - Ischemic Heart Disease

What is ischemic heart disease?

A condition in which an imbalance between myocardial oxygen supply and myocardial oxygen demand causes myocardial hypoxia and accumulation of waste metabolites; it is most often caused by atherosclerotic disease of the coronary arteries (coronary artery disease).

What determines whether the myocardium receives enough oxygen?

The balance between myocardial oxygen demand (oxygen required by the heart) and myocardial oxygen supply (oxygen delivered to the heart).

What are the two major determinants of myocardial oxygen supply?

1) Oxygen content of the blood and 2) coronary blood flow.

What are the two main coronary arteries that supply oxygenated blood to the heart?

Left main coronary artery (LM) and right coronary artery (RCA).

Where do the left main and right coronary arteries originate?

From the coronary ostia at the base of the aorta in the sinus of Valsalva.

Where are the major coronary arteries located?

On the epicardial surface of the heart.

What is the function of the major epicardial coronary arteries?

They act as low-resistance distribution vessels that deliver oxygenated blood to the myocardium.

When does most coronary blood flow occur?

During DIASTOLE rather than systole.

Why does most coronary blood flow occur during diastole?

During ventricular systole, contraction of the myocardium compresses the intramyocardial microvasculature, increasing vascular resistance and decreasing coronary blood flow.

Why is systolic compression of the coronary circulation greater in the LV than the RV?

The LV generates greater pressure and contracts more forcefully, producing greater compression of its microvasculature.

What happens to coronary perfusion when heart rate increases?

Diastole becomes shorter, leaving less time available for coronary perfusion.

Why can a high heart rate become a problem in patients with diseased coronary arteries?

Increased HR shortens diastole and therefore decreases the time available for coronary perfusion. Normal coronary arteries can compensate by dilating, but diseased coronary arteries may not be able to adequately dilate.

What is coronary blood flow directly proportional to?

Coronary perfusion pressure.

What is coronary blood flow inversely proportional to?

Coronary vascular resistance.

What can coronary perfusion pressure be approximated by?

Aortic diastolic pressure.

What is the basic relationship for coronary blood flow?

Coronary blood flow ∝ Perfusion pressure / Vascular resistance.

Why does the heart require a large amount of oxygen?

The heart has high oxidative metabolism and requires continuous ATP production.

Approximately how much oxygen in coronary arterial blood is extracted by the myocardium?

Approximately 70–75%.

Why can't the heart greatly increase oxygen extraction when myocardial oxygen demand increases?

The myocardium already extracts approximately 70–75% of available oxygen at baseline, so there is little oxygen extraction reserve.

How does the heart primarily meet an increase in myocardial oxygen demand?

By increasing coronary blood flow.

What is the relationship between myocardial oxygen demand and coronary blood flow?

As myocardial oxygen demand increases, coronary blood flow must increase because the myocardium has little additional oxygen extraction reserve.

What are the three major intrinsic factors controlling myocardial oxygen supply/coronary blood flow?

Metabolic factors, endothelial factors, and neural factors.

What happens to ATP production during myocardial hypoxia?

Aerobic metabolism and oxidative phosphorylation are impaired, causing ATP production to decrease.

What important endogenous chemicals are associated with coronary vasodilation?

Adenosine, nitric oxide (NO), and prostaglandins.

What is the overall purpose of metabolic regulation of coronary blood flow?

To match coronary blood flow and oxygen delivery to the metabolic needs of the myocardium.

How does a healthy endothelium affect coronary vascular tone?

It favors vascular smooth muscle relaxation/vasodilation because endothelial vasodilators predominate over vasoconstrictors.

What major vasodilators are produced or released by healthy endothelial cells?

Nitric oxide (NO), prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF).

What happens to vascular tone when the endothelium becomes dysfunctional, such as in atherosclerosis?

The endothelium produces reduced amounts of vasodilators, shifting the balance toward vasoconstriction.

What is prostacyclin?

An arachidonic acid metabolite released by endothelial cells that causes vascular smooth muscle relaxation and vasodilation.

What stimulates prostacyclin release?

Hypoxia, shear stress, acetylcholine (ACh), and platelet products such as serotonin.

How does prostacyclin cause vascular smooth muscle relaxation?

Through a cyclic AMP (cAMP)-dependent mechanism.

What is the overall effect of nitric oxide (NO) on coronary blood vessels?

NO is an endothelium-derived vasodilator that promotes vascular smooth muscle relaxation.

What is EDHF?

Endothelium-derived hyperpolarizing factor; a diffusible substance released by the endothelium that hyperpolarizes and relaxes neighboring vascular smooth muscle cells.

What stimulates EDHF release?

Factors including acetylcholine (ACh) and normal pulsatile blood flow.

Where is EDHF particularly important in the coronary circulation?

It is more important for modulating relaxation in small coronary arteries than in large conduit arteries.

What is endothelin-1?

A potent vasoconstrictor produced by endothelial cells that partially counteracts the actions of endothelial vasodilators.

What stimulates endothelin-1 expression?

Thrombin, angiotensin II, epinephrine, and shear stress from blood flow.

What is the overall balance of endothelial control of coronary vessels?

Vasodilators such as NO, prostacyclin, and EDHF oppose vasoconstrictors such as endothelin-1; in healthy endothelium, vasodilatory influences predominate.

What neurotransmitter is released from sympathetic nerve terminals to regulate coronary vascular tone?

Norepinephrine (NE).

What is the order of functional importance of coronary postjunctional adrenergic receptors for norepinephrine?

α1 > α2 > β2.

What happens when norepinephrine stimulates coronary α-adrenoceptors?

Increased vascular tone → vasoconstriction.

What happens when β2-adrenoceptors are stimulated in coronary vessels?

Decreased vascular tone → vasodilation.

What are the three categories you should think of when asked how coronary oxygen supply is regulated?

Metabolic → match flow to myocardial metabolism; Endothelial → balance vasodilators and vasoconstrictors; Neural → sympathetic adrenergic regulation of vascular tone.

What is the key connection between oxygen demand and oxygen supply in the normal heart?

There is a dynamic balance between the oxygen required by the myocardium and the oxygen delivered to it.

What happens when myocardial oxygen supply cannot meet myocardial oxygen demand?

Myocardial hypoxia/ischemia develops, with accumulation of waste metabolites.