Influence of reducing agents on adrenochrome-induced changes in the heart

To elucidate the role of oxidation products of catecholamines play in myocardial necrosis, we examined the effects that adrenochrome in the presence of some reducing agents and that autoxidized solution of adrenochrome have on the ultrastructure and force of contraction in the isolated rat heart. Addition of ascorbic acid (1 mM) or cysteine (0.5 mM) into a perfusion medium containing 25 mg/L of adrenochrome produced ultrastructural damage greater than that seen with adrenochrome alone, whereas addition of dithiothreitol (0.5 mM) did not. The rate of failure of the heart due to adrenochrome was accelerated by use of ascorbic acid and dithiothreitol. Reduction of adrenochrome into other oxidation products of catecholamines by these reducing agents was indicated by the results of spectral analysis studies. Myocardial damage or contractile failure did not occur if the adrenochrome solution was allowed to autoxidize for 24 hours before perfusion. These data indicate that oxidation products of epinephrine other than adrenochrome are involved in the genesis of catecholamine-induced cardiotoxicity. This effect may occur through the formation of cardiotoxic free radicals, as well as through interaction of these oxidation products with sulfhydryl groups.