PATHOPHYSIOLOGY OF ISCHEMIC HEART DISEASE



The manifestations of ischemic heart disease occur when the oxygen demand to the heart ex­ceeds the oxygen supply. The most common cause of this imbalance is fixed obstruction within a cor­onary artery. Normally the arterioles regulate the blood flow to any particular area of the heart, and the more proximal epicardial “conductance” ves­sels, in the absence of a fixed or dynamic obstruc­tion, do not restrict the flow. Once stenosis of 50 per cent or greater occurs in a conductance cor­onary artery, the vessel is unable to increase its flow sufficiently to maintain perfusion under con­ditions of increased demand despite the full di­lation of the more distal arterioles. In addition to fixed obstruction, transient or “dynamic” ob­struction of the conductance vessels may also occur. The caliber of these larger vessels can be altered by factors that are incompletely under­stood, and spasm of a localized area may decrease blood supply transiently to an area of the heaft~ (variant or Prinzmetal’s angina). Coronary artery spasm with or without the coexistent fixed cor­onary obstructive lesions may cause angina pec­toris because of a temporary decrease in oxygen supply rather than any increase in oxygen de­mand.

Occasionally oxygen demand can exceed oxy­gen supply despite normal coronary arteries; the classic example is aortic stenosis when the hy-pertrophied muscle and increased wall tension increase oxygen demand, but increased intra­mural pressure and decreased aortic pressure de­crease diastolic coronary artery flow and oxygen supply.

Ischemia affects the metabolism of cardiac cells, which can alter contractile and electrical functions. The inability to perform oxidative phosphorylation and generate highenergy com­pounds results in abnormal systolic myocardial contraction and also defects of diastolic compli­ance (relaxation). Dysfunction can be transient, for example, only after exercise-induced is­chemia, or permanent, such as with myocardial infarction. Decreased compliance requires in­creased pressure to fill the heart to any given end-diastolic volume and accounts for the need to el­evate somewhat the left ventricular filling pres­sure in order to maintain cardiac filling in patients with ischemic heart disease. The loss of cellular integrity allows release of enzymes (serum glu-tamine-ornithine transferase, lactate dehydrog­enase, and creatine kinase) into the blood that are used clinically to detect the presence of myocar­dial infarction. Electrical changes occur owing to altered ion transport across the cell membrane. Serious arrhythmias, most frequently ventricular tachycardia and fibrillation, are common.

The time during which ischemia is reversible is clinically important, since interventions exist that may restore flow to myocardium distal to an acute occlusion. Reperfusion after complete occlusion of less than 15 to 20 minutes salvages most if not all of the ischemic tissue. However, longer pe­riods of occlusion result in increased amounts of myocardium that remain irreversibly necrotic. After approximately four to six hours of occlu­sion, reperfusion salvages very little tissue.

In humans, collateral circulation (small vessels that course from a nonobstructed coronary system to the distal portion of an obstructed system) slowly develops as flow is gradually diminished by fixed coronary obstruction. Collateral flow does provide some perfusion to an ischemic vas­cular bed, but the adequacy of this perfusion is questionable, especially under periods of in­creased demand (for example, exercise). Collat­eral flow does not develop acutely after sudden obstruction of blood flow.