Effects of insulin on ventricular function in diabetic lambs with acidosis

Diabetes mellitus (DM) was induced in 10 lambs by giving alloxan (150 mg/kg). Two to 4 days later, mean values for glucose were 748 mg/dl, and for arterial pH 7.25 (acute group). Two additional lambs were studied after 3 mo of DM (chronic group). Data were compared with 7 controls (glucose 128 mg/dl, pH 7.36). Left ventricular (LV) performance was assessed from function curves and measurements of LV dP/dtmax. Stroke volume ejected at LV end-diastolic pressure of 5 cmH2O (SV5) was calculated from regression analysis of each curve. SV5 averaged 2.83 +/- 0.34 ml in controls and 2.90 +/- 0.23 ml in the acute diabetics (not significant). Mean values for LV dP/dtmax also did not differ. A significant correlation was found between SV5 and LV weight (P less than 0.001). SV5 was normalized as ml/100 g LV, and average values for the three groups were identical. Insulin (10 U/kg) caused a progressive fall in SV5 in diabetics with severe acidosis (pH 7.00), but not in those with less acidosis (pH 7.28). In nondiabetics given lactic acid (pH 7.01), SV5 fell to 60% of initial values 1 h after insulin. Acidemic animals not given insulin showed no reduction in LV performance in the same time interval. Adrenergic support is necessary to prevent cardiac failure associated with acidosis. The present findings are ascribed to inhibition by insulin of catecholamine inotropic action on myocardium.