CARDIOTOXICITY OF ADRENOCHROME IN ISOLATED RABBIT HEARTS ASSESSED BY EPICARDIAL NADH FLUORESCENCE

Noradrenaline in a micromolar concentration has recently been shown to contribute to ischemic tissue injury by direct cardiotoxic effects in dependent of functional alterations. Oxygen free radicals, generated d uring the autooxidation of catecholamines, are important mediators of catecholamine cardiotoxicity. However, the role of the oxidative produ cts (aminochromes) is still unclear. We examined the effects of adreno chrome on functional parameters and on regional myocardial ischemia (M I) in isolated electrically-driven rabbit hearts with depleted catecho lamine stores (reserpine 7.0 mg/kg i.p. 16-24 h before preparation, La ngendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca++ 1.8 mmo l/l, 37 degrees C). Repetitive MI, separated by a reperfusion period o f 50 min, was induced by coronary artery branch ligature, and MI was q uantitated from epicardial NADH fluorescence photography. Adrenochrome -treatment (10(-6) M or 10(-4) M) was started after a reperfusion peri od of 20 min. The left ventricular pressure (LVP) was significantly en hanced by adrenochrome (p < 0.05), but it fell thereafter to below its initial value in hearts treated with adrenochrome 10(-4) M. The globa l coronary flow (CF) was not affected by adrenochrome 10(-6) M (P > 0. 05), but it was significantly decreased by adrenochrome 10(-4) M (P < 0.05). The relative CF (= CF/ LVP x heart-rate) was numerically decrea sed by adrenochrome 10(-6) M (p > 0.05) and more markedly by adrenochr ome 10(-4) M (p < 0.05). Whereas epicardial NADH fluorescence was simi lar after repetitive coronary artery occlusions in controls and in hea rts treated with adrenochrome 10(-6) M (p > 0.05), it was significantl y enhanced by adrenochrome 10(-4) M (p < 0.05). In isolated rabbit hea rts, adrenochrome possesses deleterious effects on MI only at a very h igh concentration but not in a micromolar concentration. Therefore, it seems that aminochromes may be less cardiotoxic than catecholamines.