QUANTITATIVE MORPHOLOGY OF CARDIAC HYPERTROPHY

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In vitro contractile dysfunction is a result of cardiac hypertrophy that is caused by a pressure overload of the ventricular myocardium. This abnormal function occurs whether the pressure overload is from a chronic progressive or an acute overload. In contrast volume overload induced hypertrophy does not result in in vitro contractile dysfunction. In the case of the pressure overload induced hypertrophy, if this process is reversed then the contractile function returns to normal. We have studied an early stage of acute pressure overload right ventricular hypertrophy and found that there is an increase in the connective tissue components of the ventricular myocardium and a change in myocyte size and external sarcolemma surface area/ cell volume ratio. The change in connective tissue associated with pressure overload hypertrophy could contribute directly to compromised contractile performance by altering the elastic properties of the ventricle. The change in myocyte size and shape could contribute indirectly by altering the basic control systems for the contractile apparatus. The SPECIFIC AIM of this proposal is to determine whether these structural effects or other structural modifications that are found in this pathophysiological model are causally related to the impaired contractile function and therefore have etiologic significance for the eventual changes found in this model. Since the chronic progressive pressure overload model does not cause myocardial injury a comparison to the tissue from the acute pressure overload model will determine if the changes seen are a result of the myocardial injury produced by acute pressure overload. Then a comparison of the pressure overload hypertrophied right ventricular myocardium to the volume overload hypertrophied myocardium will identify those structural alterations associated with the abnormal contractile function and those associated with the hypertrophy process in general. Those alterations unique to the myocardium with contractile dysfunction should return to normal when the hypertrophy process is reversed. This will be examined in the reversed chronic progressive pressure overload model. Morphometric ultrastructural studies are used to compare and contrast the right ventricular myocardium under these different hemodynamic conditions. These studies relate to our long-term objectives which are to determine myocardial alterations that result in abnormal function and ultimately heart failure.