MEPACRINE PROTECTS THE ISOLATED RAT-HEART DURING HYPOXIA AND REOXYGENATION - BUT NOT BY INHIBITION OF PHOSPHOLIPASE A(2)

Mepacrine (quinacrine) has in a number of studies been shown to protec t the heart from ischemic injury, a protection commonly claimed to be due to inhibition of phospholipase A(2). The aim of the present study was to investigate the effect of mepacrine 1 mu M on isolated, buffer perfused rat hearts subjected to 60 min hypoxia and 30 min reoxygenati on. We also wanted to clarify whether any cardioprotective effect was due to inhibition of phospholipase A(2) or to other effects of the dru g. Mepacrine led to a substantial fall in left ventricular developed p ressure (LVDP) and coronary flow (CF) during normoxic perfusion. Treat ed hearts showed less increase in LVEDP and less fall in LVDP during t he hypoxic period, and significantly fewer hearts stopped beating comp ared to untreated controls. Release of CK during hypoxia and reoxygena tion was reduced in treated hearts compared to controls (19.9 +/- 3.8 vs. 73.1 +/- 13.3 IU, p < 0.05). Lipid analyses of the myocardium show ed a significant increase in the total amount of non esterified fatty acids (NEFA) in both untreated and mepacrine treated hypoxic hearts co mpared to normoxic controls, but to a significantly lower level in the mepacrine treated hearts. However, contribution of polyunsaturated NE FAs to total NEFAs did not differ between the groups. Also, neither to tal amount of fatty acids nor amount of polyunsaturated fatty acids ob tained from the 2-position of the phospholipid fraction differed betwe en the treated and untreated groups. In an enzyme assay, mepacrine 1 m u M did not inhibit phospholipase A(2) activity. We conclude that in o ur model mepacrine protects the heart from hypoxic injury, but probabl y by another mechanism than inhibition of phospholipase A(2) induced m embrane damage.