Cardiotoxicity of adrenochrome in isolated rabbit hearts assessed by epicardial NADH fluorescence

Abstract

Noradrenaline in a micromolar concentration has recently been shown to contribute to ischemic tissue injury by direct cardiotoxic effects independent of functional alterations. Oxygen free radicals, generated during the auto-oxidation of catecholamines, are important mediators of catecholamine cardiotoxicity. However, the role of the oxidative products (aminochromes) is still unclear. We examined the effects of adrenochrome on functional parameters and on regional myocardial ischemia (MI) in isolated electrically-driven rabbit hearts with depleted catecholamine stores (reserpine 7.0 mg/kg i.p. 16–24 h before preparation, Langendorff, constant pressure: 70 cm H₂O, Tyrode solution, Ca⁺⁺ 1.8 mmol/l, 37°C). Repetitive MI, separated by a reperfusion period of 50 min, was induced by coronary artery branch ligature, and MI was quantitated from epicardial NADH fluorescence photography. Adrenochrome-treatment (10⁻⁶ M or 10⁻⁴ M) was started after a reperfusion period of 20 min. The left ventricular pressure (LVP) was significantly enhanced by adrenochrome (p<0.05), but it fell thereafter to below its initial value in hearts treated with adrenochrome 10⁻⁴ M. The global 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×heart-rate) was numerically decreased by adrenochrome 10⁻⁶ M (p>0.05) and more markedly by adrenochrome 10⁻⁴ M (p<0.05). Whereas epicardial NADH fluorescence was similar after repetitive coronary artery occlusions in controls and in hearts treated with adrenochrome 10⁻⁶ M (p>0.05), it was significantly enhanced by adrenochrome 10⁻⁴ M (p<0.05). In isolated rabbit hearts, adrenochrome possesses deleterious effects on MI only at a very high concentration but not in a micromolar concentration. Therefore, it seems that aminochromes may be less cardiotoxic than catecholamines.