T3 C

thus myocardial O2 demand are raised. Should this continue over a long period, the ventricular myocardium will hypertrophy p. 224 ff.). This reduces wall tension, at least for a while (compensation). Decompensation occurs when the heart weight has reached the critical value of500 g, at which time the ventricle dilates (^ p. 224 ff.). The radius of the ventricular cavity and thus wall tension increases, so that O2 demand now suddenly rises to very high values.

Consequences and symptoms of myocardial ischemia. The myocardium covers its energy requirement by metabolizing free fatty acids, glucose, and lactate. These substrates are used for the O2-dependent formation of ATP (^ C, normal). When blood supply is interrupted (ischemia), this aerobic energy gain stagnates, so that ATP can only be formed nonaerobically. Lactatic acid is now produced, dissociating into H+ ions and lactate. In these circumstances not only is lactate not used up, it is actually produced (^ C, early "ischemic anoxia"). The ATP yield is thus quite meagre and, furthermore, the H+ ions accumulate because of the interrupted blood flow, both events being responsible for abnormal ventricular contraction (reversible cell damage; ^ C). If the ischemia persists, glycolysis is also inhibited by tissue acidosis, and irreversible cell damage occurs (infarct; see below) with release of intracellular enzymes into the blood (^C, left).

ATP deficiency leads to:

♦ Impairment of the systolic pumping action of the ventricle (forward failure; ^p. 224ff.) as well as

♦ Decreased compliance of the myocardium during diastole (backward failure; ^ p. 224 ff.), so that the diastolic atrial and ventricular pressures are raised.

♦ Congestion in the pulmonary circulation (dyspnea and tachypnea). Just before ventricular systole the lowered compliance in diastole produces a fourth heart sound that originates from the increased atrial contraction ("atrial gallop"). If the papillary muscles are affected by the ischemia, this may result in

♦ Finally, disorder of myocardial excitation caused by the ischemia (^E) may precipitate dangerous arrhythmias (ECG; ^ p. 186 ff.). During the ischemia period the ECG will show an elevation or depression (depending on the lead) of the ST segment as well as flattening or reversal of the T wave (similar to that in F4). If the resting ECG of a patient with angina is normal, these ECG changes can be provoked by controlled (heart rate, blood pressure) physical exercise.

Stimulation of the nociceptors (by kinins?, serotonin?, adenosine?) will lead not only to

- anginal pain (see above), but also to

- generalized activation of the sympathetic nervous system with tachycardia, sweating, and nausea.

Therapeutic attempts at restoring an even O2 balance (^ p. 217 C) in patients with angina are:

♦ Lowering myocardial O2 consumption (p-adrenergic blockers; organic nitrates that reduce the preload [and to some extent also the afterload] by generalized vasodilation; Ca2+ channel blockers), and

♦ Increasing the O2 supply (organic nitrate and Ca2+ channel blockers that both function to counteract spasm and to dilate coronary vessels). In addition, the size and position of the atherosclerotically stenosed coronary arteries make it possible to dilate them by balloon angioplasty or vascular stents or by revascularization with a surgically created aortocor-onary bypass.

Myocardial Infarction

Causes. If the myocardial ischemia lasts for some time (even at rest [unstable angina]; see above), tissue necrosis, i.e., myocardial infarction (MI), occurs within about an hour. In 85% of cases this is due to acute thrombus formation in the region of the atherosclerotic coronary stenosis.

This development is promoted by

- turbulence, and

- atheroma rupture with collagen exposure. Both events

- activate thrombocytes (aggregation, adhesion, and vasoconstriction by release of thromboxan). Thrombosis is also encouraged through

- abnormal functions of the endothelium, thus its vasodilators (NO, prostacyclin) and an-tithrombotic substances are not present

D. Acute Ischemia in Coronary Atherosclerosis

Atheroma

D. Acute Ischemia in Coronary Atherosclerosis

Atheroma

Thrombus (local, embolic)

Thrombus (local, embolic)

—*

Dilated

Constricted

Dilated

Constricted

Circumference of muscle ring

100%

95%

100%

95%

Internal radius (mm)

0 0

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