Mepacrine, a phospholipase inhibitor. A potential tool for modifying myocardial reperfusion injury.

Cardioprotective effects of phospholipase inhibitor, mepacrine, on ischemic reperfused myocardium were investigated in the isolated in situ pig heart preparation, which was subjected to 120 minutes of regional ischemia, with the final 60 minutes having superimposed global cardioplegic arrest followed by 60 minutes of reperfusion. Mepacrine (0.05 mmol/L) was administered before ischemia into the perfusion circuit in 15 of 29 experiments. Significant depletion of myocardial phospholipids occurred in nontreated animals during 60 minutes of reperfusion. Mepacrine prevented the reperfusion-induced phospholipid degradation. Further, the level of high-energy phosphate compounds was higher during ischemia and reperfusion in the mepacrine-treated hearts. Left ventricular developed pressure, maximum rate of rise of left ventricular pressure, and left ventricular end-diastolic pressure were measured under isovolumic conditions to assess cardiac contractility and compliance. During incubation with mepacrine, before ischemia, left ventricular developed pressure and maximum rate of rise of left ventricular pressure decreased to 45% and 51% of baseline values, respectively. This initial decline was improved to 65% and 70% in mepacrine-treated animals during the early period of regional ischemia. In the nontreated control heart, a progressive decline in contractility was observed with ischemia such that no significant difference was apparent in the two groups. Reperfusion resulted in a further deterioration of global cardiac performance in both mepacrine-treated and control animals. Although pretreatment with mepacrine did not improve contractility, myocardial oxygen consumption, coronary flow, and cardiac compliance significantly improved. These results suggest that myocardial injury may develop during reperfusion after temporary ischemia. Mepacrine inhibits such injury by acting as a phospholipase inhibitor, but it also behaves as a negative inotropic agent in ischemic reperfused myocardium.