Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart.

Observations are presented which suggest that myocardial cellular hypoxia may account for the reduction in myocardial ATP and CP in the ketoacidotic diabetic state. It is suggested that reduced 2,3-diphosphoglycerate adversely affects oxygen release from the red blood cell, thereby leading to myocardial cellular hypoxia.

The extent of tissue oxygenation in patients with diabetes mellitus has been the subject of several recent reports in the literature (Alberti, et al., 1972; Ditzel, 1972; Bellingham, et al., 1970). The criterion of tissue oxygenation used in these studies was the P50, the oxygen tension at 50% hemoglobin saturation. Interpretation of these results is difficult in that both increased and decreased P50’s were reported. The conditions varied from acute ketoacidosis to non-acidotic, ambulatory patients receiving insulin. An increased P50 was associated with the acute ketoacidotic stage of diabetes while a decreased P50 was associated with insulin treatment.