Pathophysiology of ischemic heart disease

Abstract Recent clinical and experimental studies have helped to clarify the pathophysiology of acute and chronic coronary insufficiency, particularly in the area relating myocardial ischemia to abnormal function of the damaged left ventricle. When proximal vessel stenosis due to coronary atherosclerotic disease becomes the major locus of resistance to coronary blood flow, there is a decline in perfusion pressure distal to the stenosis. This results in ischemia when the normal mechanism for autoregulating coronary flow (i.c., coronary arteriolar vasodilatation) is no longer adequate to maintain flow. Formation of collaterals is important in maintaining flow and function and, in experimental infarction, may protect almost completely against slow occlusion of a major vessel. Speed of vessel closure is therefore important; if this is sudden, myocardial necrosis may occur before collaterals are able to form. It also is clear that relatively small changes in the degree of stenosis and in coronary flow, or relatively slight increases in myocardial oxygen requirement, may cause ischemia. When critical coronary stenosis is present, small imbalances in myocardial oxygen supply and demand may cause transient or, if sustained, permanent muscle injury and dysfunction. Thus, in patients with coronary artery disease, stresses that increase myocardial oxygen demand (exercise, isoproterenol infusion, or rapid pacing) may precipitate transient episodes of coronary insufficiency. Quantitatively left ventricular failure occurs when approximately 25% of the ventricular muscle is damaged. This results both from absolute loss of functioning myocardium and from asynchrony of contraction due to aneurysmal ballooning of the injured zone. With irreversible injury, gradual scarring and stiffening of the infarct often occur, resulting in some improvement of function. The improvement may also be due in part to enhanced contractile performance of the uninjured normal myocardium. However, some patients develop progressive cardiac dilatation or form large aneurysms, which may be related to extent of myocardial injury. In patients who succumb to cardiogenic shock 50% or more of the left ventricle may be damaged. Newer approaches to therapy of myocardial ischemia include attempting to restore blood flow to the ischemic area or to improve the balance of oxygen supply and demand in the marginally injured cells surrounding the infarct. Oxygen demand is strongly influenced by ventricular size and wall stress. Current studies emphasize the dynamic interplay of wall stress and contractile state: in nonfailed ventricles with focal ischemic lesions inotropic interventions may extend the area of infarction; in the dilated ventricle the opposite may be the case, provided that the net result of increased inotropy is a reduction in ventricular size. A more direct approach through assisted circulation or surgical revascularization of the myocardium is also under study. The ultimate utility of these methods in clinical myocardial infarction depends upon reversibility of ischemic myocardial injury, and this remains to be defined in various clinical settings.