Functional effects of adrenochrome in isolated rabbit heart

The cardiotoxic effects of catecholamines have been explained in part by the generation of oxygen free radicals and aminochromes. The role of aminochromes remains however controversial. It has previously been demonstrated that adrenochrome, an oxidation product of adrenaline, shows cardiotoxic properties only at very high concentrations, and it has been suggested that the deleterious effects observed may be caused by a worsening in myocardial perfusion. The functional properties of adrenochrome were examined in isolated spontaneously-beating rabbit hearts with depleted catecholamine stores (reserpin 7.0 mg/kg 16-24 hr before preparation, Langendorff, constant pressure: 70 cm H2O, Tyrode solution, [Ca++]sol. 1.8 mmol/l, 37 degrees). Cumulative concentration-response curves show an adrenochrome-concentration-dependent increase of contractility (left ventricular pressure, EC50 = 3.6 x 10(-6) M; +dp/dtmax, EC50 = 1.6 x 10(-5) M), whereas myocardial relaxation was impaired (-dp/dtmax, EC50 = 2.6 x 10(-5) M; -dp/dtmax/+dp/dtmax = 0.68 at 10(-4) M). Heart-rate was only slightly enhanced (+10% at 10(-4) M), and the coronary flow was markedly influenced only by adrenochrome 10(-4) M (-17%). The relative coronary flow (= global coronary flow/pressure-rate product) was concentration-dependently reduced (EC50 = 10(-5) M; -49% at 10(-4) M). We conclude that in isolated rabbit hearts, adrenochrome has a positive inotropic action but impairs myocardial relaxation, and coronary constrictor activity prevents an increase of myocardial oxygen supply, thus worsening myocardial oxygen-demand/supply balance.