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Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle.

Utilization of carbohydrate and fatty acids is strongly influenced by rates of con­ sumption and production of high energy compounds in cardiac muscle. In well­ oxygenated hearts, fatty acid has been identified as the preferred substrate by both in vivo and in vitro studies (for review see 146). Availability of fatty acid suppresses glucose utilization by inhibition of several steps in the glycolytic pathway. Since a variety of longand short-chained fatty substrates are inhibitory and since the effect is abolished in hearts perfused under anaerobic conditions, oxidation of the fatty acid appears to be required for this effect. When energy utilization of well­ oxygenated hearts is increased, consumption of fatty acids and/or glucose is ac­ celerated. Under these conditions, fatty acids remain the preferred oxidative substrate. Availability of oxygen to the heart can be restricted either by lowering or reducing to zero the oxygen tension of the perfusate, thereby inducing hypoxia or anoxia, or by restricting the flow of perfusate containing high oxygen tensions to induce ischemia. In hypoxic or anoxic hearts, fatty acid oxidation is suppressed and glycol­ ysis is stimulated. The acceleration of flux through glycolysis may be as much as 10to 20-fold. On the other hand, ischemia results in only a transient increase in glycolytic flux that is followed within 3-4 min by inhibition. Fatty acid oxidation is suppressed in ischemic hearts leading to accumulation of long-chained CoA derivatives and increase in triglyceride levels.