Influence of hypoxia and hyperoxia on the cardiovascular and lethal effects of ethanol.
The mutual potentiation of the hepatotoxic effects of ethanol and hypoxia raised the question of whether such an interaction also occurs in the cardiovascular system. Therefore, anaesthetized rats were infused intravenously with ethanol (25 mg/kg x min.) over 90 min. to reach blood ethanol concentrations between 2.2 and 2.6 g/l and were ventilated artificially either with room air, 10% O2/90% N2 or 100% O2. Under normoxic conditions, ethanol produced a slow decrease of mean arterial blood pressure from 130 to 100 mmHg due to the decline in cardiac output and stroke volume (-20%) while heart rate and peripheral resistance remained unchanged. Hypoxia (arterial oxygen tension 35-38 mmHg) without ethanol produced immediate hypotension (-60 mmHg) without decreasing the cardiac output, i.e. by reducing peripheral resistance. In combination with ethanol, hypoxia produced an even stronger hypotension (-90 mmHg) due to reduction in both cardiac output and peripheral resistance. On the other hand, respiration with 100% O2 (arterial oxygen tension about 500 mmHg) elevated peripheral resistance, attenuated ethanol-induced cardiodepression and prevented ethanol-induced hypotension. The lethal doses of ethanol evaluated by infusing 75 mg/kg x min. ethanol until death amounted to 4.1 g/kg with 10% O2, to 5.5 g/kg with 20% O2 (room air) and to 6.9 g/kg with 100% O2. Thus decrease in vascular contractility induced by hypoxia combined with ethanol-induced cardiodepression may result in lethal cardiovascular failure. Hyperoxia, on the other hand, counteracts ethanol-induced cardiodepression and its acute toxicity by raising the vascular contractility.
Strubelt
O
O
Institute of Toxicology, Medical University of Lübeck, Germany.
Younes
M
M
D000758:Anesthesia; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D018496:Hyperoxia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol