Ventricular pressure-heart rate product before induction of ischemia as a determinant of the reperfusion-induced accumulation of calcium within myocardium

Using the product of heart rate (HR) and left ventricular developed pressure (LVP) as a measure of the total mechanical energy required for contraction (TMEFC), experiments were performed with isolated perfused heart preparations of the guinea pig to establish the importance of TMEFC before induction of ischemia for induction of calcium accumulation within ischemic reperfused myocardium. Two calcium antagonists, diltiazem and nicardipine, and prazosin produced a dose-related suppression of the calcium accumulation when given prior to induction of ischemia (except for the highest dose of nicardipine), while they were ineffective when given only during the period of reperfusion, and the suppression was found to be closely correlated with the decrease in HRxLVP before induction of ischemia. The failure of the highest dose of nicardipine to suppress calcium accumulation (while producing a dose-related decrease in HRxLVP) was not associated with an increase in cyclic AMP. These findings are compatible with the idea that TMEFC before induction of ischemia is a prime determinant of calcium accumulation within the ischemic reperfused myocardium.