Rats fed a diet high in fat and low in protein continuously infused by intragastric cannula were given ethanol for 2 to 6 months in order to examine the response of liver adenine nucleotides to changes in systemic POz. Hepatic adenine nucleotides were measured in vivo monthly using liver obtained by biopsy from rats while a high blood alcohol level was maintained. Ethanol decreased hepatic ATP and the total adenylate pool, but did not change the levels of ADP and AMP. Adenylate energy charge showed only a tendency to be decreased. Carotid arterial POz was mildly but significantly lower in ethanol-fed rats compared to the pair-fed controls. Pure Oz inhalation for 3 min increased the POz four times in the ethanol and control-fed rats, and tended to increase ATP and decrease ADP in ethanol-fed rats as well as pair-fed controls. It restored the energy charge to a normal level in the ethanol-fed rats. Ten per cent Oz + 90% Nz inhalation for 3 min decreased the POz to 40 mm Hg in both the ethanol-fed and control rats, and this rapidly decreased ATP. This effect was significantly greater in the ethanol-fed rats compared to the controls. The total adenylate pool and the energy charge were decreased only in ethanol-fed rats. The results show that the reduced energy stores in the rat liver induced by ethanol are rapidly responsive to changes in POz. Thus, the livers of ethanol-fed rats were more vulnerable to transient hypoxia than were controls.
Since ATP is involved at various steps of intermediary metabolism, acting as an energy source in cells, cellular intermediate metabolism may be adversely effected when ATP levels are decreased. Both chronic ethanol ingestion and hypoxia may affect metabolism by lowering ATP levels and energy charge. Chronic administration of ethanol may affect ATP levels and decrease energy metabolism by impairing mitochondrial functions as measured in uitro (1-4). The abnormalities in ATP levels ( 5 ) and mitochondrial respiratory control (6) induced by ethanol feeding are rapidly reversed by ethanol abstinence. However, attempts to correlate ATP levels sequentially with liver pathology induced by ethanol have not been made.