Cardiovascular effects of acetaldehyde accumulation after ethanol ingestion: their modification by beta-adrenergic blockade and alcohol dehydrogenase inhibition.
Left ventricular function was examined by echocardiography and systolic time intervals in nine healthy male volunteers, who ingested ethanol 0.35 g/kg 4 hr after a 50-mg peroral dose of calcium cyanamide, an aldehyde dehydrogenase inhibitor. Accumulation of acetaldehyde in blood was accompanied by marked increases in heart rate (53%) and cardiac output (78%) as well as by decreases in diastolic arterial blood pressure (19%) and peripheral vascular resistance (46%). Ejection fraction and maximum circumferential fibre shortening velocity increased by 25 and 47%, respectively; the preejection period/ejection time ratio decreased by 31%. 4-Methylpyrazole, an alcohol dehydrogenase inhibitor, efficiently reduced blood acetaldehyde levels when injected intravenously (7 mg/kg) at the height of the reaction. It was as effective as intravenous propranolol (0.1 mg/kg) in attenuating the hyperdynamic circulation and stabilized arterial blood pressure better than propranolol. We conclude that even a very mild alcohol intoxication (30-50 mg/100 ml) causes a marked enhancement of cardiac function, in addition to vasodilation, in subjects with impaired acetaldehyde oxidation. These changes are reversed by preventing acetaldehyde formation through alcohol dehydrogenase inhibition.
D000079:Acetaldehyde / Q000097:blood*; D000328:Adult; D000426:Alcohol Dehydrogenase; D000428:Alcohol Drinking; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors*; D000435:Alcoholic Intoxication / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003484:Cyanamide / Q000627:therapeutic use*; D003486:Cyanides / Q000627:therapeutic use*; D004452:Echocardiography; D000431:Ethanol / Q000097:blood; D000077604:Fomepizole; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D011433:Propranolol / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use
D003486:Cyanides; D011720:Pyrazoles; D000431:Ethanol; D003484:Cyanamide; D000077604:Fomepizole; D011433:Propranolol; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D000079:Acetaldehyde