Pathophysiology of ischemia in patients with coronary artery disease

Abstract

C ORONARY atherosclerosis is characterized by subintimal thickening that leads to plaque formation and stenosis.’ During the progression of this pathology in the large epicardial arteries, episodes of transient myocardial ischemia occur and each event is characterized by a reversible decrease in regional myocardial oxygen concentration that characteristically effects a segment of the left ventricle.2 This leads to the failure of systolic and diastolic muscle function, varying degrees of left ventricular failure, and profound metabolic disturbances. This functional expression of coronary artery disease can be induced by provoking disturbances in coronary blood supply and/or increases in myocardial demand for oxygen (ie, during exercise); ischemia also occurs during the activities of everyday life and it can precede damaging clinical events such as acute myocardial infarction, pulmonary edema, and sudden death.?,’ Transient myocardial ischemia in patients with obstructive coronary artery disease occurs in many different clinical syndromes (eg, chronic stable angina, unstable angina, and after myocardial infarction) and its presence always indicates the increased risk of adverse coronary events.2-7 In the majority of patients with ischemia and proven coronary artery disease, there are atherosclerotic stenoses that severely reduce crosssectional area in a segment of at least one epicardial artery. In these circumstances, standardized exercise protocols can provoke and reproduce ischemia and angina at a reproducible level of exercise. These clinical features have nurtured the belief that coronary blood supply is fixed and myocardial demand increases to cause ischemia. Although this concept is useful when considering the benefits of beta-adrenoreceptor blocking drugs, coronary angioplasty and by-pass graft surgery, these therapies probably do not address the disturbed biology of developing atherosclerotic lesions. Clinical studies of transient myocardial ischemia during daily life,8*9 studies of regional myocardial blood flow before and during ischemia”‘-I5 and studies of coronary vasomotion during cardiac catheterization all highlight the active role of the diseased epicardial arteries in causing transient ischemia.16-r9 An enhanced understanding of the biology of atherosclerotic stenoses has clarified pathophysiological mechanisms of myocardial ischemia and has suggested new directions in the development of therapies aimed at physical regression of coronary atherosclerosis and the control of constriction and thrombosis.20.2i This article will focus on transient myocardial ischemia by examining new clinical characteristics and pathogenic mechanisms rather than simply evaluating diagnostic techniques. It will discuss new clinical information about the biology of atherosclerosis and stenoses in relation to the occurrence of ischemia and adverse clinical outcomes. New insights from basic research will only be discussed as they provide fresh directions for clinical research. This paper will focus on transient ischemia rather than myocardial infarction or sudden death and will try to explore the relationship between coronary atherosclerosis, coronary vasoconstriction, and thrombosis as these problems occur in patients.