title: Protective effects of an indenoindole antioxidant on coronary endothelial function after long-term storage.
abstract: Experiments were designed to evaluate function of the endothelium and smooth muscle of coronary arteries following storage of hearts in cardioplegia containing an inhibitor of lipid peroxidation (H 290/51, cis-7-methyl-9-methoxy-5,5a, 6,10b tetrahydroindeno [2,1-b] indole). Canine hearts were perfused with crystalloid cardioplegia (Plegisol, 15 ml/kg, 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 without (group IV, n = 6) addition of H 290/51. The final concentration of H 290/51 was 1 mumol/L. Arteries were removed, cut into rings, and suspended in organ chambers for measurements of isometric force. In selected rings, the endothelium was removed in order to study the function of the smooth muscle. In order to discriminate effects of ischemia/reperfusion and protective properties on coronary endothelium or smooth muscle, drugs with different mechanisms were used. The function of the 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 arteries from hearts that were not stored. Endothelium-independent relaxations to isoproterenol and nitric oxide among the different groups were comparable. These results suggest that storage of canine hearts with crystalloid cardioplegia selectively inhibits endothelium-dependent relaxations mediated by receptor activation. Inhibition of lipid peroxidation with H 290/51 preserves these relaxations and may therefore represent a therapeutic alternative to preserve hearts used for transplantation.
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D000001:Calcimycin / Q000494:pharmacology; D002314:Cardioplegic Solutions; D003331:Coronary Vessels / Q000502:physiology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D016027:Heart Transplantation; D007211:Indoles / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D014021:Tissue Preservation
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000975:Antioxidants; D002314:Cardioplegic Solutions; D007211:Indoles; D011810:Quinoxalines; D009569:Nitric Oxide; C057286:indenoindole; D000001:Calcimycin; D000068438:Brimonidine Tartrate; D007545:Isoproterenol; D001920:Bradykinin