Abstract 138: Disadvantageous Effects of Carvedilol on Mortality and Inflammatory Responses to Endotoxin-Induced Shock in Rats
Background Recent studies showed that beta-blocker suppressed the LPS-induced cytokine and tissue factor in vitro and attenuated myocardial dysfunction in septic animals. However, our previous report showed that 10mg/kg/day Carvedilol increased mortality rate and did not inhibit inflammatory responses in endotoxic rats. The purpose of this study is to evaluate the dose-effects of Carvedilol on mortality and inflammatory responses to endotoxin-induced shock in rats.
Methods Fifty-three male Sprague Dawley rats were randomly assigned to one of the following four groups, control group (n=12): no medication, high-dose treatment group (H group) (n=12): Oral administration of Carvedilol (10mg/kg/day ) for 5 days, medium-dose treatment group(M group)(n=15):Carvediolol (5mg/kg/day) for 5 days, low-dose treatment group(L group)(n=14):Carvedilol (2mg/kg/day) for 5 days. All animals were anesthetized with intraperitoneal pentobarbital. Endotoxic shock was induced by 15 mg of endotoxin injection. There were no therapies before, during or after endotoxin injection. Hemodynamics and arterial blood gases were evaluated, and mortality rate were assessed for the 8-hr observation period. Plasma cytokine concentrations were measured at baseline, 2, 4 and 5-hr after endotoxin injection.
Results The mortality rates at 8-hrs after endotoxin injection was 17%, 71%, 73% and 75% for control, L, M, H group, respectively. The mortality rates in the all treatment groups were significantly higher than that in the control group (P<0.05). There was no dose-response relationship on survival rate among each treatment groups. Blood pressure and heart rate was significantly lower in the treatment groups.
Conclusion This study indicates that any doses of Carvedilol have disadvantage effects on mortality and inflammatory responses to endotoxin-induced shock in rats.
- © 2011 by American Heart Association, Inc.