Arrhythmia susceptibility and myocardial composition in diabetes. Influence of physical conditioning.

Abnormal myocardial composition in diabetes mellitus has been described, but the effects on ventricular vulnerability have not been defined. We have assessed the susceptibility to arrhythmias in a canine model after 1 yr of mild diabetes induced by alloxan. Since physical conditioning can affect metabolic abnormalities in diabetes, this intervention has also been evaluated. Group 1 served as controls and groups 3 and 4 were diabetic. Animals in the latter group as well as nondiabetic controls of group 2 were exercised on a treadmill for the last 8 mo of the experiment. After 1 yr, anesthesia was induced with chloralose for vulnerability studies. The ventricular fibrillation threshold of 24.4 +/- 1.9 mA in group 3 was significantly less than in normals (45.1 +/- 2.2). Spontaneous arrhythmias were also more prevalent in diabetics during acute ischemia (group 3-A). Increased ventricular vulnerability after epinephrine infusion was present in the sedentary diabetes despite normal ventricular function responsiveness. In a superfused preparation of myocardium, resting membrane potential and action potential amplitude were normal in diabetics, and beta-adrenergic stimulation shortened repolarization more than in controls. Myocardial collagen concentrations, which included an interfibrillar distribution on morphologic examination, were increased in group 3. In the trained diabetics of group 4 the basal vulnerability thresholds and responses to epinephrine were normal. While myocardial collagen levels were normal, cholesterol and triglyceride increments persisted. Thus, in mild experimental diabetes, enhanced susceptibility to arrhythmias exists; this susceptibility may be based on a combination of nonhomogenous collagen accumulation affecting local conduction and increased electrophysiologic sensitivity to catecholamines.

Relation of growth hormone and myocardial collagen accumulation in experimental diabetes.

A pathogenic role of growth hormone in the tissue complications of diabetes has been postulated. Because collagen has been found to accumulate in myocardial interstitium in diabetes, we have undertaken a study of the relationship of plasma growth hormone levels to collagen accumulation in a canine model of chronic diabetes. Sedentary normal animals and diabetic animals were compared respectively with physically conditioned animals in which the collagen increment associated with diabetes was minimized. Basal growth hormone levels as well as increments induced by hormone release after clonidine have been related to the myocardial alteration. Myocardial collagen concentration was increased to 2.94 +/- 0.11 micrograms/mg dry weight in the sedentary diabetic animals vs. 1.97 +/- 0.07 micrograms/mg dry weight in sedentary normals (P less than 0.01), but was normal in the exercised diabetic animals after 1 year. However, levels of growth hormone in the basal state were similar in all four groups. After provocative stimulation with clonidine in the normals there was a progressive rise of growth hormone levels that was similar in the sedentary and physically conditioned animals. The diabetic groups exhibited a rise of plasma growth hormone that was not significantly higher in the nonexercised animals. Moreover the peak levels of growth hormone after clonidine were comparable. The data suggest that collagen accumulation in diabetic myocardium does not appear to be dependent on increased plasma levels of growth hormone, but a role for enhanced sensitivity to hormonal action is not excluded.