This is a multidisciplinary proposal to explore the fundamental pathophysiology and biochemistry of ischemic and infarcted myocardium and to implement knowledge of the pathophysiology of this disease into programs to: (1) identify those at risk of serious ischemic events and (2) examine means for improving the management of those patient manifesting ischemic heart disease. Studies of the metabolism of ischemic myocardium will utilize nuclear magnetic resonance to identify rapid changes in energy state. The importance of shape changes, relaxation characteristics of myocardium and ischemic and scarred myocardium as determinants of left ventricular function will be examined in animal models and man. The role of prostaglandins in ischemia and in the mechanism of action of cardiac active drugs will be explored. We will attempt to identify the anatomic predictors of sudden cardiac death invasively and non-invasively as well as explore risk factor profile in relationship to anatomic coronary lesions and prognosis. We will explore the therapeutic potential of a new automatic implantable defibrillator device in man. Randomized clinical intervention trials will include: (1) nitroglycerin plus propranolol in low risk patients with acute infarction (vs. placebo); (2) intraaortic balloon pumping and nitroglycerin in high risk patients with acute infarction (vs. routine therapy); (3) new vs. conventional cardiopulmonary resuscitative techniques; (4) a slow channel blocker (vs. placebo) in patients with unstable angina pectoris; (5) a membrane active anti-arrhythmic agent vs. placebo in survivors of acute infarcts assessed to be at high risk of subsequent sudden death and (6) use of perioperative agents for decreasing complications of coronary bypass surgery. Core support laboratories include: Pathology, Nuclear Cardiology, Echocardiography and Pharmacology.
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