influence of experimentally induce, non-insulin dependent diabetes on the extent of myocardial injury in a canine ischaemia-reperfusion model

ABSTRACT

Diabetes mellitus is a well known risk factor for coronary artery disease and subsequent myocardial infarction. The present study evaluated the effect of short term [12 weeks] experimentally induced non-insulin-requiring diabetes on the extent of myocardial injury in a canine ischaemia-reperfusion model and investigated the underlying biochemical mechanisms. Non-insulin-dependent diabetes was induced in 10 dogs by the streptozotocin-alloxan method and another 10 dogs were used as controls. On the day of the experiment, dogs of either group were weighted and blood samples were withdrawn from the anticubital vein for biochemical and lipid determinations. Dogs were then anaesthetised and myocardial infarction was provoked by occluding the left anterior descending coronary artery [LAD] for 1 hour followed by 3 hours reperfusion. Biopsies were taken from the center of the LAD bed before and then after the 4 hours of the whole occlusion/reperfusion technique. Twelve weeks following diabetes induction, diabetic dogs had higher fasting blood glucose, fructosamine, cholesterol, triglycerides, and apo B concentrations than control dogs. Plasma insulin level was significantly lower in diabetic dogs than controls. Also, plasma antioxidants vitamin E and A were significantly lower in diabetics than in controls on the day of the surgical procedure. Capillaries of the diabetic myocardium showed thickening of basal lamina. The diabetic cardiocytes revealed scalloping of sarcolemma and changes in the Z line in the form of thickening, irregularity and loss of alignment. Light bands were seen in many areas along the myofibrils. After ischaemia-reperfusion, severe ultrastructural changes were observed in the diabetic cardiocytes. Myofilaments showed disruption, lysis and fragmentation. Mitochondrial changes and widening of intercalated discs were also noticed. From the previous study, we cannot identify exactly the mechanism[s] by which diabetes aggravated myocardial injury. The results nevertheless suggest that one reason why myocardial ischaemia is less well tolerated in diabetics than in non-diabetics is likely to be by inducing myocardial ultrastructural changes. This may partly explain the poor prognosis of myocardial infarction in diabetic persons