PROTECTIVE EFFECTS OF AN INDENOINDOLE ANTIOXIDANT ON CORONARY ENDOTHELIAL FUNCTION AFTER LONG-TERM STORAGE

Experiments were designed to evaluate function of the endothelium and smooth muscle of coronary arteries following storage of hearts in card ioplegia containing an inhibitor of lipid peroxidation (H 290/51, cis- 7-metyl-9-methoxy-5,5a, 6,10b tetrahydroindeno [2,1-b] indole). Canine hearts were perfused with crystalloid cardioplegia (Plegisol, 15 ml/k g, 4 degrees C) and left circumflex arteries were isolated and studied either immediately (group I, n=6), or after storage of the hearts at 4 degrees C for 10 (group II, n=6) or 24 hr with (group III, n=6) or w ithout (group IV, n=6) addition of H 290/51. The final concentration o f H 290/51 was 1 mu mol/L. Arteries were removed, cut into rings, and suspended in organ chambers for measurements of isometric force. In se lected rings, the endothelium was removed in order to study the functi on of the smooth muscle. In order to discriminate effects of ischemia/ reperfusion and protective properties on coronary endothelium or smoot h muscle, drugs with different mechanisms were used. The function of t he endothelium were studied with the alpha(2)-adrenergic agonist UK 14 ,304, bradykinin and A 23187. The smooth muscle function were studied with isoproterenol and nitric oxide, Endothelium-dependent relaxations to the alpha(2)-adrenergic agonist UK 14,304 and bradykinin, but not to A 23187, were reduced significantly in arteries from hearts stored for 24 hr in cardioplegic solution alone. Relaxations of arteries from hearts stored for 24 hr with H 290/51 were comparable to those arteri es from hearts that were not stored. Endothelium-independent relaxatio ns to isoproterenol and nitric oxide among the different groups were c omparable. These results suggest that storage of canine hearts with cr ystalloid cardioplegia selectively inhibits endothelium-dependent rela xations mediated by receptor activation. Inhibition of lipid peroxidat ion with H 290/51 preserves these relaxations and may therefore repres ent a therapeutic alternative to preserve hearts used for transplantat ion.