title: Effects of carvedilol on mortality and inflammatory responses to severe hemorrhagic shock in rats.
abstract: The nonselective beta-adrenoceptor and the selective alpha1-adrenoceptor blocker carvedilol are widely used in hypertensive and/or cardiac failure patients because of its efficacy. However, there have been few studies regarding the effects of carvedilol on severe hemorrhagic shock. The present study was performed to evaluate the effects of carvedilol on severe hemorrhagic shock in rats. Twenty-four male Sprague-Dawley rats were randomly assigned to 1 of the following 2 groups (n = 12 per group): control group, no medication; and treatment group, oral administration of carvedilol (10 mg/kg per day) for 5 days. All animals were anesthetized with i.p. pentobarbital. Severe hemorrhagic shock was induced by partial exsanguination. Eight minutes after shock, all removed blood was returned to the animal. No other treatments were administered before, during, or after shock. Hemodynamics and arterial blood gases were recorded, mortality was calculated for the 5-h observation period, and plasma cytokine concentrations were measured at 5 h after shock. The mortality rates at 5 h after cardiac arrest were 8% and 50% for control and treatment groups, respectively. The increases in base deficit and lactate concentrations were less in the control group than that in the treatment group. Moreover, the increases in TNF-alpha concentrations were less in the control group than in the treatment group. The present study indicated that oral administration of carvedilol had adverse effects on mortality and inflammatory responses to severe hemorrhagic shock in rats. These findings suggest that carvedilol may adversely affect recovery from severe hemorrhagic shock.
authors.affiliation: Department of Emergency and Critical Care Medicine, Graduate School of Medical Science, Kanazawa University, Japan. takutaniyan@yahoo.co.jp
authors.forename: Takumi
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Akihide
authors.initials: A
authors.lastname: Kurita
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Inaba
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000097:blood; D000077261:Carvedilol; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D010100:Oxygen / Q000097:blood; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D014409:Tumor Necrosis Factor-alpha; D000077261:Carvedilol; D002245:Carbon Dioxide; D010100:Oxygen