Effects of diabetes on myocardial perfusion in the atherosclerotic monkey

We examined the influence of diabetes on the severity of coronary atherosclerosis, as judged by coronary morphometric and blood flow studies. Cynomolgus monkeys were fed a coconut-peanut oil mixture plus cholesterol to induce the plaque lesions of atherosclerosis in nondiabetic (group 2) and diabetic monkeys (group 3). Group 1 consisted of chow-fed controls. After 18 months of hypercholesterolemia, the animals were anesthetized to assess myocardial blood flow, by use of radioactive microspheres. Transmural and inner/outer wall flow ratios were normal in the two lipid-fed groups in the basal state. Vasodilation after adenosine (0.45 mg/kg/min IV) elicited a more than threefold rise of transmural blood flow in group 1, and a significantly reduced increment in groups 2 and 3. The blood flow ratio was not different from unity in group 1 but declined to 0.69 +/- 0.03 in group 2 and 0.69 +/- 0.06 in group 3, with similar decrements of heart rate and aortic pressure. In contrast to results in group 1, left ventricular filling pressure rose and velocity of contractile elements declined to a similar extent in groups 2 and 3 after adenosine, consistent with myocardial ischemia. Morphometric measurements as well as chemical analyses were performed on the three major coronary arteries. The degree of intimal thickening and increase of cholesterol and collagen content were comparable in groups 2 and 3. Thus, in this model the plaque lesions of atherosclerosis did not appear to be intensified by diabetes. Moreover, the responses to adenosine in terms of myocardial underperfusion and mechanical dysfunction were comparable in the two experimental groups.