Abstract P224: Effects Of Oral Administration Of Carvedilol On Mortality And Inflammatory Responses To Endotoxin-induced Shock In Rats
Recent studies show that Carvedilol, nonselective beta-adrenoceptor and selective alphal-adrenoceptor blocker, is widely used in hypertensive and/or cardiac failure patients. Moreover, several studies show that Carvedilol and beta-blocker suppress the LPS-induced production of cytokine and tissue factor in vitro and attenuate myocardial dysfunction in septic animals. However, there are few studies about the effects of oral administration of Carvedilol during sepsis. The current study was to evaluate the effects of oral administration of Carvedilol on endotoxin-induced shock in rats. Twenty-four male Sprague Dawley rats were randomly assigned to one of the following two groups (n=12 per group), control group: no medication, treatment group: oral administration of Carvedilol (10 mg/kg/day) for 5 days. All animals were anesthetized with pentobarbital ip. Shock was induced by 15 mg of endotoxin iv. There were no therapies before, during or after endotoxin injection. Hemodynamics and arterial blood gases were evaluated, and mortality rate were calculated for the 8-hr observation period. Plasma cytokine concentrations were measured at baseline, 2, 4 and 5-hr after the endotoxin injection. The mortality rates at 8-hrs after endotoxin injection were 17% and 75% for the control and the treatment groups, respectively. The mortality rate in the treatment group was significantly higher than that in the control group (P=0.003). The increases in base deficit and lactate concentrations were less in the control group than the treatment group. Moreover, the increases of TNF-alpha concentrations were less in the control group than in the treatment group. The present study showed that oral administration of Carvedilol had the disadvantages on mortality and inflammatory responses to endotoxin-induced shock in rats. These findings suggest that Carvedilol may worsen the recovery of septic shock.