Diltiazem treatment of endotoxic shock in suckling rats

Gram-negative sepsis septic shock continues to produce significant mortality and therefore remains a major medical problem. Vasodilators have been studied in the treatment of circulatory shock. However, the effectiveness of calcium channel blockers in the treatment of newborn endotoxic shock has not been well documented. In the present study, diltiazem, a calcium channel blocker, and nitroprusside, a vasodilator, were used for the treatment of endotoxic shock in 10-day-old rats. Mortality rate, hemodynamics, and glucose metabolism were monitored. Diltiazem at a dose of 0.3 mg/kg attenuated the hypotension, bradycardia, hypoglycemia, and lactacidemia in newborn endotoxic shock. Diltiazem treatment resulted in reduced 24-hour mortality. However, 0.6 mg/kg diltiazem enhanced the hypotension, bradycardia, and lactacidemia in endotoxic shock. Nitroprusside blunted the hypoglycemia and decreased the mortality rate among rats with endotoxic shock. Afterload reduction may be responsible for the beneficial effects of 0.3 mg/kg diltiazem and nitroprusside. Diltiazem at a dose of 0.3 mg/kg reduced the lactacidemia of endotoxic shock more than nitroprusside. Therefore the effects of diltiazem may be due not only to afterload reduction but also to inhibition of cellular calcium influx. We conclude that 0.3 mg/kg diltiazem and 1.0 mg/kg nitroprusside are beneficial for the treatment of endotoxic shock in newborn rats.