This grant will test the hypothesis that resistance of the myocardial fiber to shortening-determines the energy cost of contraction. In post-ischemic myocardial dysfunction (stunning), we have observed that end-diastolic length and also the delay that occurs from the onset of local force-development to the beginning of segment shortening are markedly prolonged, and can be shortened by isoproterenol. Under various conditions, efficiency of myocardial contraction (regional segment work / regional myocardial oxygen consumption) varies over a range of at least 100-150%. It is proposed that the relative elastance of each myocardial segment largely controls local myocardial efficiency, and determines the extent of global energy loss. Experiments will be performed and a mathematical model will be constructed to test this hypothesis by producing local and global changes in elastance (passive and time- varying) and observing the effect on local and global myocardial efficiency. In open-chest anesthetized dogs, local segment length and developed force will be measured simultaneously in myocardium supplied by the left anterior descending and circumflex coronary arteries respectively. LV pressure and volume will also be measured. Regional and global LV work will be calculated on-line by integration of the length-force and volume-pressure loops during systole. Regional and total LV coronary blood flow will be measured with radioactive microspheres, and microspectrophotometric determination of regional O2 saturations as well as coronary sinus oximetry will be used to calculate regional and global MVO2 respectively. The effects of induced changes in end-diastolic volume, contractility, and heart rate during regional and global ischemia and reperfusion of varying durations on these parameters will be measured. A mathematical model of regionally impaired ventricular contraction will consist of normal and impaired regions. Each region will have a prescribed dynamic pressure- volume relationship and will be permitted to interact with each other, the arterial load, and a filling reservoir. The purpose of the model will be to help explain and suggest basic relationships for the observed data. Information obtained from this study will provide a quantitative understanding of factors controlling oxygen cost of local contraction, and may lead to management of coronary insufficiency by treatment aimed at increasing efficiency.
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