Arterial levels, cardiac and hepatic arteriovenous differences, extraction coefficients and oxygen extraction ratios of various substrates in normal, and in acute and chronic alloxan-diabetic dogs.

Arterial levels and cardiac and hepatic arteriovenous differences (AVD), extraction coefficients and oxygen extraction ratios of glucose, lactate, pyruvate, free fatty acids, aceto-acetate, 3-hydroxybutyrate, citrate and oxygen were determined simultaneously by catheter techniques in anaesthetized (chloralose-urethane) normal, and in acute and chronic alloxan-diabetic dogs. The differences in mean values between the normal and the diabetic groups were tested for their significance by analysis of variance and the dependence of AVD values on their corresponding arterial levels by correlation analysis. 1 The arterial levels of glucose, free fatty acids, acetoacetate and 3-hydroxybutyrate were significantly raised in both diabetic groups. Citrate was significantly elevated only in the acute diabetic animals. Arterial pyruvate was significantly lowered in both diabetic groups. Arterial pH values of around 7.24 were found in the acute diabetic animals. 2 Cardiac AVD of glucose was significantly reversed in the acute diabetic dogs. The myocardial AVD of pyruvate and lactate were positive in normal, and significantly negative (except lactate in chronic diabetes) in both diabetic groups. A significant, positive correlation between myocardial AVD and arterial levels was obtained for lactate in the normal group and for pyruvate in normal and diabetic animals. Arterial lactate/pyruvate ratios were significantly correlated to arterial lactate and pyruvate levels in the diabetic animals. Myocardial AVD and oxygen extraction ratio values of free fatty acids were not significantly changed in the diabetic groups, but myocardial free fatty acids extraction coefficient values were significantly reduced. The myocardial AVD and oxygen extraction ratio values of acetoacetate and 3-hydroxybutyrate were significantly increased in both diabetic groups. A positive correlation between AVD and the corresponding arterial levels of free fatty acids and acetoacetate was obtained in normal dogs. Myocardial citrate AVD and oxygen extraction ratio were significantly raised in the acute diabetic animals. 3 The hepatic AVD of glucose, lactate and pyruvate were negative (release) in normal animals. No significant change in hepatic glucose AVD was found in the diabetic animals, yet the hepatic AVD of lactate and pyruvate became significantly positive (uptake). A highly significant, positive correlation between hepatic AVD and the arterial level of pyruvate was obtained in normal and in diabetic animals, the regression line of the diabetic animals being shifted to a 10-fold lower range of arterial levels. The hepatic AVD of free fatty acids was significantly raised in the acute diabetic dogs and significantly correlated to the arterial free fatty acids level in normal and diabetic animals, with almost identical regression lines. The hepatic AVD of acetoacetate and 3-hydroxybutyrate were negative in all animals but significantly more negative in the diabetic groups. A positive, significant correlation was obtained between AVD and the arterial level of acetoacetate in normal dogs and between the hepatic release of ketone bodies and the hepatic uptake of free fatty acids within all groups. The mean values of hepatic AVD of citrate were negative in all groups, the most negative values being found in the acute diabetic animals. The hepatic oxygen AVD was significantly doubled in the chronic diabetic group.