Myocardial and coronary vascular responses to insulin in the diabetic lamb

Diabetes mellitus was produced in 9 lambs by giving alloxan monohydrate, 150 mg/kg, 24 h prior to study, and these were compared with 12 control animals. Responses to insulin, 20 U/kg, were studied in each. Measurements of LV dP/dtmax, coronary sinus flow (CF) and myocardial extraction and uptake of O2, glucose and fatty acids (NEFA) were made using a hemodynamically controlled preparation described previously (Am. J. Physiol. 244: 1381, 1973). Initial arterial glucose (G) averaged 328 mg/dl in the diabetics compared with 110 mg/dl in controls. G fell to 160 mg/dl 90 min after insulin in the diabetics, and to 25 mg/dl in the controls. Initial LV dP/dtmax values were identical in both groups and showed similar increases of about 800 mmHg/s 30 min after insulin (P less than 0.001). However, initial CF was lower and resistance higher in diabetics than controls. After insulin, CF increased 50% in controls but only 10% in diabetics. Because inotropic responsiveness and O2 metabolism were the same in both groups, altered coronary vascular smooth muscle reactivity in the diabetics may explain these findings.