Myocardial cell damage and cardiovascular changes due to i.v. infusion of adrenochrome in rats

In vivo effects of adrenochrome (1-32 mg/kg), an oxidation product of catecholamines, on the heart ultrastructure, ECG and blood pressure were studied in rats over a period of 60 min following a single i.v. injection of the drug. One milligram of the drug had no influence on the myocardium or the cardiovascular system, whereas maximum changes in these parameters were recorded at 32 mg/kg of adrenochrome. The maximum structural damage, reached within 5-10 min, included marked swelling of mitochondria and sarcotubular system, intracellular and perinuclear oedema, hypercontraction of myofibrils and partial separation of the intercalated disc. Ultrastructural changes in the myocardium due to 4 and 8 mg of adrenochrome were not accompanied by any cardiovascular effects and the changes were fully reversed within 60 min of the injection of the drug. However, at 16 and 32 mg/kg of adrenochrome both heart rate and blood pressure were depressed within 5 min of drug administration. At these concentrations of adrenochrome arrhythmias, mainly due to premature ventricular contractions, were also noticed. Ultrastructural and cardiovascular changes seen at these higher concentrations of adrenochrome showed only a partial recovery. The data indicates that adrenochrome-induced ultrastructural changes in the heart are due to a direct myocardial effect of the drug which may not involve haemodynamic changes and the latter are most probably a consequence of this effect. However, the present study has not been able to rule out direct vascular effects at higher concentrations of adrenochrome.