Research Project
3473933
Despite meticulous adherence to modern myocardial management principles during invasive cardiological procedures or cardiac surgical repairs, REGIONAL postischemic cardiac dysfunction manifest as depressed GLOBAL left ventricular (LV) performance persistently contributes to postinterventional morbidity and mortality. Although preload optimization, afterload reduction and inotropic support often effect gross clinical improvement, it is NOT fully known what mechanical or energetic expense these classical therapeutic modalities may impart to recovering regions of the myocardium. Using new methods of assessing cardiac mechanisms, energetics and chemomechanical transduction developed in GLOBAL models of ischemia, the present studies propose to develop a model of REGIONAL cardiac energy transfer that will characterize the mechanical and energetic deficits attendant to protected and unprotected regional cardiac ischemia. Recovery from GLOBAL cardiac ischemia involves a shift in the total LV work from the external mechanical to the internal cardiac work compartment and is associated with an augmented postischemic myocardial oxygen utilization thought necessary to (1) repair damaged cell membranes and organelles (2) to restore disrupted transmembrane ionic gradients (e.g. calcium) and (3) to resume normal excitation-contraction coupling and contractile function. REGIONAL postischemic recovery is further complicated by heterogeneity of fiber distribution (anterior (thin) versus posterior (thick) myocardium), of tissue catecholamine and receptor density and of dynamic mechanical linkages between ischemic and non-ischemic zones. Accordingly, the present studies propose to (1) define preload, afterload and heart rate independent linear indices of regional contractility; (2) correlate regional myocardial oxygen utilization indices; (3) quantitate regional energy transfer attendant to alterations in loading and contractile state conditions as well as consequent to the altered myocellular oxygen utilization after both protected and unprotected cardiac ischemia. It is hoped the results of these investigations will contribute new information to develop alternative ameliorative and supportive strategies for recovering postischemic regions of myocardium and as a consequence reduce the morbidity and mortality related to interventional cardiological and cardiac surgical procedures.
