Nisoldipine inhibits lipid peroxidation induced by coronary occlusion in pig myocardium

Abstract

The aim was to investigate the effect of the Ca++ channel blocker nisoldipine on the content of lipid peroxidation products in pig myocardium after acute coronary occlusion. Open chest pigs were subjected to the occlusion of the left anterior coronary artery (LAD) with or without nisoldipine. After 30 min ischaemia, myocardial samples were taken from the ischaemic area and from the non-ischaemic posterior wall of the left ventricle for determination of lipid peroxidation products. Subjects were farm pigs of either sex. In 10 pigs, the LAD was occluded without drug pretreatment; 11 pigs were infused with nisoldipine (10 micrograms.kg-1) 30 min before the LAD occlusion. Sham operated controls received no drug (n = 7) or nisoldipine (n = 9). Myocardial samples were assayed for the content of lipid peroxidation products: malondialdehyde, conjugated double bonds, and fluorescent end products. Plasma nisoldipine concentration was measured in some experiments. Following the LAD occlusion, the content of lipid peroxidation products increased in both ischaemic and non-ischaemic myocardial regions as compared to the hearts of sham operated pigs. Pretreatment with nisoldipine completely prevented these increases. At a time of the coronary occlusion, plasma nisoldipine concentrations were within the therapeutic range. Ca++ antagonist prevents the excessive peroxidation of myocardial membrane lipids which affects the whole myocardium when there is acute local ischaemia. Prevention of myocardial damage in the non-ischaemic region may determine survival of the infarcted heart.