Coronary artery ligation and reperfusion in rabbits made diabetic with alloxan

The biochemical and functional changes associated with ligation (40 min) of the left circumflex coronary artery and subsequent reperfusion (60 min) in the rabbit made diabetic with alloxan were studied and compared with those of control animals. Measurement of haemodynamic parameters revealed that both left ventricular pressure and mean arterial pressure were significantly (P less than 0.05) decreased after ligation and reperfusion in the diabetic animals compared with controls. Analysis of subcellular organelle enzyme markers from the ischaemic tissue revealed that sarcolemmal Na+,K+-ATPase, mitochondrial ATPase and sarcoplasmic reticulum ATPase activities were decreased after ligation to the same extent in the diabetic and control animals. However, upon reperfusion, the recovery of mitochondrial ATPase activity was significantly (P less than 0.05) less in the diabetic animals than in the controls. Ion measurements revealed a significant (P less than 0.05) depletion of Mg in diabetic hearts before ligation, and this was augmented during reperfusion. In contrast, a significantly (P less than 0.05) higher calcium accumulation was observed upon reperfusion in the hearts of diabetic animals. Similarly, both tissue ATP levels and the ability of the mitochondria to generate ATP were depressed to a greater degree in the diabetic animals. Our results indicate, therefore, a greater susceptibility of the diabetic myocardium to ischaemic/reperfusion injury which in the clinical situation would exacerbate the problems associated with atherosclerosis and possibly contribute to the high mortality from cardiovascular complications in diabetic patients.