Previous studies have shown contractile defects for some forms of experimental cardiac hypertrophy; however, because of the complex organization of myocardial tissue, which is comprised of cardiac muscle cells embedded in a network of neural, vascular and inter- stitial cells, it has not been possible until recently to determine whether the contractile defect observed for the myocardial tissue is an intrinsic property of the cardiac muscle cell (cardiocyte) itself, or a property of the cardiac muscle cell within its interstitium. The advent of the helium-neon laser has made it possible to measure sarcomere shortening in isolated cardiocytes, and therefore to study the contractile properties of these cells without the confounding influence of the surrounding myocardial tissue; accordingly, this technique will be used to study the contractile function of cardiocytes isolated from right and left ventricular hypertrophy models during exposure of such cells to two sets of defined in vitro loading conditions: first, unloaded peak velocity and extent of sarcomere shortening will be studied in buffer solution; second, a relation between the extent and velocity of sarcomere shortening vs. load will be established using a technique unique to our laboratory, wherein the load on an individual cardiocyte is varied as a function of the viscosity of the solution external to the cell. The first specific aim of this proposal is to establish whether the contractile defect in an experimental model of right ventricular pressure overload hypertrophy is a property of the cardiocyte itself, or whether instead it is a property of a normal cardiocyte functioning within an abnormal interstitial environment. Two considerations have led us extend our studies to left ventricular hypertrophy models: first, left ventricular disease is far more important clinically than is right ventricular disease; second, in contrast to the behavior of the corresponding right ventricular models, experimental left ventricular volume overload usually leads to contractile dysfunction whereas pressure overload usually does not. Thus the second specific aim of this proposal is to extend the same question of cardiocyte vs. myocardial tissue contractile function to the left ventricle. These studies will accomplish two goals: first, they will focus future research regarding the contractile defect in hypertrophied myocardium either on the cardiac muscle cell itself, or the cardiac muscle cell within its interstitium; second they will answer the question of whether there is an intrinsic difference in the contractile defect that develops in experimental models of right and left ventricular hemodynamic overload.
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