This multidisciplinary investigation of the pathogenesis, progression, and favorable modification of ischemic heart disease involves 27 investigators from 13 departments engaged in 11 research projects and 5 cores laboratories. Coronary vascular pathogenetic mechanisms are the focus of studies of attenuation of ultrasound, contractile properties, and prostaglandin metabolism in normal and diseased vessels. Improved quantification of regional myocardial ischemia and infarction are being pursued by delineation of processes governing release and disappearance of biochemical markers of necrosis (MB and mitochondrial CK) and the distribution of positron-emitting tracers detected by computer reconstruction tomography. Etiological roles of amphipathic lipids and regional adrenergic stimulation in the genesis of malignant dysrhythmia and of calcium flux in the precipitation of cell death in myocardium and the microvasculature will be characterized to provide a basis for more effective prophylaxis and therapy. Clinical projects are devoted to improved detection of regional myocardial ischemia and infarction with positron tomography; characterization of early recurrent infarction and identification of the roles of implicated etiological factors such as platelets and coronary vasospasm with enzymatic, scintigraphic, and tomographic approaches; and identification of biochemical and physiological determinants of early and late dysrhythmia including the extent of initial infarction and prevailing concentrations of circulating amphipathic lipids in patients at rest and with exercise. Studies involve several levels of biological organization including isolated cells, vessels and myocardium in vitro, isolated perfused hearts, experimental animal preparations, and patients. Although the scope is broad, the techniques required have been implemented, verified, and in several cases developed during the initial grant interval with each project therefore predicated on a substantial base of information already acquired.
