ISCHEMIC-HEART-DISEASE AND ANTIOXIDANTS - MECHANISTIC ASPECTS OF OXIDATIVE INJURY AND ITS PREVENTION

The disease state of myocardial ischemia results from a hypoperfusion- induced insufficiency of heart-muscle oxidative metabolism due to inad equate coronary circulation. Myocardial ischemia is an important, life span-limiting medical problem and a major economic health-care concern . Reperfusion, although avidly pursued in the clinic as essential to t he ultimate survival of acutely ischemic heart muscle, may itself carr y an injury component Cardiac reperfusion injury appears to reflect, a t feast in part, an oxidant burden established upon reoxygenation of i schemic myocardium. Laboratory evidence demonstrates that oxidative st ress to the heart-muscle cell (cardiomyocyte) can elicit the three kno wn types of ischemia-reperfusion injury that directly affect the myoca rdium: arrhythmia, stunning, and infarction. The limited clinical occu rrence of serious reperfusion arrhythmias has restricted the importanc e of antioxidants as antiarrhythmic agents against this form of myocar dial ischemia-reperfusion damage. Despite the utmost clinical signific ance of lethal cardiomyocyte injury as a negative prognostic indicator for the ischemic heart-disease patient, inconsistent results of antio xidant interventions in reducing infarct size have somewhat tempered i nterest in antioxidant infarct trials. By contrast, the negative clini cal consequences of stunning may indeed be preventable by utilizing an tioxidants to help restore postischemic cardiac pump function. Several as yet unanswered questions remain regarding oxidative stress in the reperfused heart, its significance to cardiomyocyte damage, and its ab ility to elicit specific postischemic myocardial derangements. Targete d mechanistic studies are required to address these questions and to d efine the pathogenic role of oxidative stress (and hence, the therapeu tic potential of antioxidant intervention) in myocardial ischemia-repe rfusion injury. The overall aim of current research in this area is to enable the cardiac surgeon/cardiologist to advance beyond the largely palliative drugs now available for management of the coronary heart-d isease patient and attack directly the pathogenic determinants of hear t-muscle ischemia-reperfusion injury. Optimal use of antioxidants may help address this important medical need.