Myocardial contractile function is a commonly used marker of cell viability. However, mechanical function may be an inadequate index of cell viability since failure to recover contractile function following ischemia and reperfusion is not synonymous with cell death. Alterations in compounds of oxidative or anaerobic metabolism may be more indicative of cell viability and the ability of the heart to maintain or recover mechanical function. The loss of high energy phosphate stores or accumulation of lactate during anaerobic metabolism has been associated with ischemia induced myocardial dysfunction. It would be ideal to determine the serial in vivo changes of these compounds during and following myocardial ischemia in order to assess if these compounds may be used to predict reversibility of postischemic contractile dysfunction. Until recently, biopsies of myocardial tissue were necessary to evaluate the metabolic products of oxidative and anaerobic metabolism. Recent technological advances in nuclear magnetic resonance (NMR) spectroscopy now allow measurements of these compounds in a serial , nondestructive manner in vivo. Previously, the conventional method for measurement of regional mechanical function in animals utilized the transit-time technique which required tow ultrasound crystals; one sutured to the epicardium and the other imbedded into the subendocardium. This procedure caused considerable trauma and difficulty in maintaining alignment of the two crystals during an experiment. A newly developed epicardial Doppler ultrasound crystal technique has overcome these limitations and allows assessment of segmental myocardial contractility in a nontraumatic, noninvasive manner. Thus, using NMR techniques in conjunction with epicardial Doppler measurements of mechanical function, a unique method for rapid serial for vivo measurements metabolic and mechanical changes that occur with myocardial ischemia and reperfusion is possible. We propose to utilize these techniques to determine serially in vivo cardiac changes of high energy phosphate compounds and lactate during and following ischemia and relate these changes to the changes in myocardial contractility in order to determine if one of these compounds can be used to predict reversal of post-ischemic myocardial dysfunction. With the advent of in vivo NMR techniques applicable to man, this work may be useful in assessing the changes of cardiac metabolism and mechanical function that may occur following interventions designed to limit myocardial ischemia.
