Effects of terbutaline on circulatory failure and organ dysfunction induced by peritonitis in rats

Abstract

Objective: The pathogenesis of multiple organ dysfunction syndrome (MODS) in septic shock is mainly caused by maldistribution of tissue perfusion and the amplification of inflammatory responses, which may be modulated by beta(2)-adrenoceptor agonists. We evaluated and compared effects of terbutaline on MODS in a cecal ligation and puncture (CLP) model of sepsis.

Design and setting: Prospective controlled animal study in a university laboratory.

Methods: Male adult Wistar rats received CLP or sham operation followed by the administration of saline or terbutaline (0.3 mg/kg i.v. at 3 and 9 h after CLP).

Measurements and results: At 0, 9 and 18 h after CLP, the changes of hemodynamics, organ function indexes, as well as the plasma interleukin-1beta (IL-1beta) and nitrite/nitrate levels were examined. At 18 h after CLP, animals were killed and their lungs, livers and kidneys were immediately excised to analyze superoxide anion (O(2) (-)) levels and inducible nitric oxide synthase (iNOS) expression. These organs were also evaluated by pathological study. Terbutaline significantly (1) prevented delayed hypotension and reduced hepatic and renal dysfunction, (2) diminished plasma IL-1beta and nitrite/nitrate, lung iNOS expression, tissue O(2) (-) level and the infiltration of neutrophils in the lung and the liver, and (3) improved the 18-h survival rate.

Conclusions: Terbutaline may be developed as an alternative treatment for severe sepsis-induced MODS. The protective effect of terbutaline seems to be through inhibition of proinflammatory mediators and attenuation of oxidant production.