Cardiac performance of isolated perfused hearts from alloxan diabetic rats

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Abstract
Acute alloxan diabetes (3 days) in the rat resulted in a decreased ability of the isolated perfused working heart to respond to increased atrial filling pressure with normal systolic (aortic) pressure development, using a physiologic concentration of glucose (5 mM) as substrate. The diabetic heart also exhibited impaired cardiac output which was due to decreased aortic output without any apparent effect on coronary flow. This decrease in ventricular performance was accompanied by a 40% reduction in glucose uptake and a 20% reduction in tissue ATP concentrations even though perfusate glucose levels remained at or near physiologic levels. Perfusion of hearts with 5 mM glucose plus 10-8 M insulin, with 10 or 30 mM glucose, or 1 mM octanoate reversed the diabetes-related decrease in systolic pressure development, cardiac output and tissue ATP content. The defect in cardiac performance with increased work loads associated with acute insulin deficiency is apparently due to the relative inability of the heart to utilize physiologic concentrations of glucose as substrate for energy production.