CALCIUM OVERLOAD DURING REPERFUSION IS ACCELERATED IN ISOLATED HYPERTROPHIED RAT HEARTS

In this study, calcium overload during reperfusion and the severity of morphologically evident ischemic myocardial injury were compared in h ypertrophied and normal hearts. Hypertrophied hearts isolated from rat s where a clip had been placed on the proximal thoracic aorta for 6 we eks were compared to those from sham-operated rats in an isolated stat e perfused with Krebs-Henseleit buffer containing 3% albumin, 1.2 mM p almitate and 11 mM glucose. The isolated hearts were exposed to global , no-flow, normothermic ischemia following potassium arrest and were r eperfused. Following ischemia and reperfusion, left ventricular end di astolic pressure was increased (39+/-7 v 13+/-2 mmHg, P<0.05), and per centage recovery of left ventricular systolic function was decreased ( 34.4+/-8.9 v 77.1+/-6.3% P<0.05), in hypertrophied hearts compared to control hearts. Calcium overload during reperfusion was two and one-ha lf times greater in the hypertrophied hearts than in the control heart s and showed significant relationships with recovery of left ventricul ar systolic function (r=-0.86, P<0.001) and left ventricular end diast olic pressure (r=0.78, P<0.005). Myocardial energy charge did not diff er between the two groups at the end of reperfusion. Ischemic myocardi al injury was quantitated morphologically by point counting techniques in a comparable series of control and hypertrophied hearts. After isc hemia, hearts were either exposed to a monoclonal antimyosin antibody to identify and measure irreversibly injured myocardium by light micro scopy of fixed by perfusion with 2.5% glutaraldehyde to quantitate the morphologic changes ultrastructurally. Control and hypertrophied hear ts were not significantly different in severity of myocardial injury d ue to ischemia as assessed morphologically. Thus, the data suggest tha t calcium overload during reperfusion plays a significant role in post -ischemic left ventricular dysfunction of the hypertrophied heart. The accelerated calcium overload that occurs in the hypertrophied rat hea rt during reperfusion cannot be explained by differences in severity o f myocardial injury during ischemia which indicates that other mechani sms are responsible.