Influence of diabetes on the myocardium and coronary arteries of rhesus monkey fed an atherogenic diet.

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Abstract
To examine the influence of diabetes on the progression of coronary atherosclerosis and primary myocardial alterations in the rhesus monkey, a Purina or atherogenic diet was fed to nondiabetic animals of groups 1 and 2, respectively, and also to groups 3 and 4 with alloxan diabetes. After 18 mo., cardiac studies were performed, by indicator dilution in the intact anesthetized state, at similar levels of heart rate and aortic pressure. Despite comparable basal hemodynamics, preload increments with saline evoked a stroke work response that was significantly less in both diabetic groups. Left ventricular end-diastolic pressure rose from 10.1 .+-. 1.4 mm Hg to 20.5 .+-. 2.7 in group 3, and from 11.1 .+-. 2.1 to 24.0 .+-. 3.3 in group 4, which were significantly higher elevations than occurred in the controls. End-diastolic volume rose much less in diabetics. Indices of contractility as well as left heart weight were normal. Hydroxyproline concentrations were 4.98 .+-. 0.33 g/mg dry wt in group 1, 5.16 .+-. 0.24 in group 2, 8.4 .+-. 0.35 in group 3 and 7.1 .+-. 0.37 in group 4. Soluble collagen was significantly diminished and the insoluble fraction enhanced in diabetics and was the apparent basis for enhanced wall stiffness. The collagen increment was most evident between myofibers. Cardiac cell organelles by EM, tissue cation concentrations, as well as the myocardial lactate response to pacing, were within normal limits. Cholesterol content of the coronary arteries, as a measure of the early atherosclerotic process observed as lipid streaks, was similarly increased in the nondiabetic and diabetic monkeys on lipid diets, with respective plasma cholesterols of 367 .+-. 55 and 409 .+-. 62 mg/100 ml. The diabetic-Purina group had a lower but significantly elevated coronary artery cholesterol, associated with higher plasma glucose and nonsterol lipid levels. In this primate model, diabetes did not intensify either the early coronary lesions induced by moderate hypercholesterolemia, nor were the myocardial changes associated with diabetes altered by the presence of moderate hypercholesterolemia.