The nitrefazole-ethanol interaction in man: cardiovascular responses and the accumulation of acetaldehyde and...

The cardiovascular effects of ethanol ingestion after pretreatment with a new antialcohol drug, nitrefazole (2-methyl-4-nitro-1-(4-nitro-phenyl)imidazole, Altimol) were studied. Left ventricular function was examined by echocardiography and systolic time intervals in six healthy Finnish male volunteers who ingested 0.15-0.25 g of ethanol/kg, 24 hr after an 800 or 1600-mg peroral dose of nitrefazole. After ethanol ingestion, accumulation of acetaldehyde in blood (25-150 microM) was accompanied by a 1.5-2-fold increase in plasma noradrenaline, a 3-10-fold increase in plasma adrenaline, and a 0.5-2.0 degrees C rise in skin temperature. Heart rate increased by 70% and cardiac output by 107%. Diastolic blood pressure decreased by 30% and peripheral vascular resistance by 54%. Ejection fraction and maximum circumferential fiber-shortening velocity increased by 26 and 71%, respectively; the pre-ejection period/ejection time ratio decreased by 46%. An apparent vasovagal collapse was noticed in two nitrefazole-treated subjects after ethanol ingestion, and a third subject experienced a fainting attack shortly after the experiment. Thus, in subjects pretreated with nitrefazole, ingestion of rather small amounts of ethanol results in marked accumulation of acetaldehyde apparently due to aldehyde dehydrogenase inhibition. This causes elevation of plasma catecholamines and intense enhancement of cardiac performance. The marked cardiovascular changes demonstrate the potency of nitrefazole, suggesting that, particularly with alcoholics with occult myocardial diseases, its interaction with ethanol may be even more hazardous than that produced by other antialcohol drugs.