Effect of diltiazem on altered glucose regulation during endotoxic shock

Endotoxic shock is associated with profound metabolic alterations including hypoglycemia and hyperlactiacidemia. We studied hepatic glucose production and the role of diltiazem in affecting these metabolic alterations in a rat model of endotoxic shock. Fasted rats were intravenously injected with saline, endotoxin (20 mg/kg), endotoxin (20 mg/kg) plus diltiazem (1.2 mg/kg), or saline plus diltiazem. Five hours after the injections, the rats were anesthetized and blood samples were obtained for plasma glucose and lactate. The livers of all rats were then perfused in situ with an oxygenated 37 degrees C glucose-free Hanks' balanced salt solution at a rate of 30 ml/min via the portal vein and effluent was collected from the inferior vena cava. After 30 min equilibration, 5 mM lactate was added to the perfusate as a gluconeogenic substrate. Endotoxic groups exhibited hypoglycemia (64.5 +/- 12.7 mg/dl) and hyperlacticacidemia (4.3 +/- 0.63 mM). Diltiazem administration improved the hypoglycemia (96.9 +/- 9.1 mg/dl) and attenuated the hyperlacticacidemia (2.2 +/- 0.7 mM) in the endotoxic group. Gluconeogenic stimulation with lactate was demonstrated in both the control (18.1 +/- 2.3 vs 12.8 +/- 1.86 microns/g/hr, P < .05) and endotoxic (16.6 +/- 2.3 vs 9.8 +/- 1.1, P < .05) groups. However, stimulation in the endotoxic groups was significantly less compared with control. Gluconeogenic stimulation in the endotoxic group was unaffected after diltiazem administration. These data suggest that diltiazem treatment in endotoxic shock improves hypoglycemia and attenuates hyperlacticacidemia. These metabolic alterations are not associated with an improvement in substrate-specific stimulation of gluconeogenesis.