The development of ischemic contracture and subsequent contraction band necrosis has been known to be more rapid in the hypertrophied than non-hypertrophied heart, and to occur first in the subendocardial layers of the left ventricle. The temporal correlation of metabolic abnormalities with structural alterations is much less clear, and the influence of non-hemodynamic factors on the development of subendocardial necrosis has received very little study. The hypothesis being tested is that there are metabolic differences in cardiac myocytes of subendocardial versus subepicardial tissue which occur independant of pressure and flow related changes and that these differences are accentuated in cardiac hypertrophy. These metabolic changes render the subendocardium more susceptible to ischemic cell death. We plan to study the development of cellular metabolic and structural changes in the isolated rat heart arrested with KC1 and under constant left ventricular pressure to avoid the influence of hemodynamic variables in the intact heart. We will utilize the isolated myocyte preparations to study myocyte response to anoxic conditions a) without the influence of other cellular components, and b) after one to two days and 1 and 2 weeks in culture to provide further temporal removal from in vivo hemodynamic effects. We will use morphological methods to identify time and location of ischemic myocardial alterations in relation to regional metabolic alterations in these normal and hypertrophied hearts. HPLC analysis will be used to quantitatively evaluate regional differences in adenine nucleotides and their metabolites. Finally, myosin isozymes will be analyzed to evaluate changes which may have occurred in contractile protein properties in hypertrophied myocardium. The results of these studies should provide information correlating metabolic and morphologic changes in hypertrophied myocardium and provide a better understanding for the increased susceptibility of the hypertrophied heart to ischemic heart disease.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Cardiovascular Study Section (CVA)
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University of Alabama Birmingham
School of Medicine & Dentistry
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