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29 January 2009

Effects of dobutamine on gut mucosal nitric oxide production during endotoxic shock in rabbits

Suzana M. LoboACEF, Francisco G. SorianoDE, Denise F. BarbeiroD, Daniel De BackerDE, Qinghua SunB, Zizhi TuB, George DimopoulosB, Jean-Charles PreiserA, Bernard VrayAG, Vincent VercruysseB, Jean-Louis VincentAEG

Med Sci Monit 2009; 15(2): BR37-42 :: ID: 869546

Abstract

Background
Dobutamine is the agent of choice for increasing cardiac output during myocardial depression in humans with septic shock. Studies have shown that beta-adrenoceptor agonists influence nitric oxide generation, probably by modulating cyclic adenosine monophosphate. We investigated the effects of dobutamine on the systemic and luminal gut release of nitric oxide during endotoxic shock in rabbits.
Material and Method
Twenty anesthetized and ventilated New Zealand rabbits received placebo or intravenous lipopolysaccharide with or without dobutamine (5 micro g/kg/min). Ultrasonic flow probes placed around the superior mesenteric artery and the abdominal aorta continuously estimated the flow. A segment from the ileum was isolated and perfused, and serum nitrate/nitrite levels were measured in the perfusate solution and the serum every hour.
Results
The mean arterial pressure decreased with statistical significance in the lipopolysaccharide group but not in the lipopolysaccharide/dobutamine group. The abdominal aortic flow decreased statistically significantly after lipopolysaccharide administration in both groups but recovered to baseline in the lipopolysaccharide/dobutamine group. The flow in the superior mesenteric artery was statistically significantly higher in the lipopolysaccharide/dobutamine group than in the lipopolysaccharide group at 2 hours. The serum nitrate/nitrite levels were higher in the lipopolysaccharide group and lower in the lipopolysaccharide/dobutamine group than those in the control group. The gut luminal perfusate serum nitrate/nitrite level was higher in the lipopolysaccharide group than in the lipopolysaccharide/dobutamine group.
Conclusions
Dobutamine can decrease total and intestinal nitric oxide production in vivo. Those effects seem to be inversely proportional to the changes in blood flow.

Keywords: Perfusion, Nitrites - blood, Rabbits, Nitric Oxide - biosynthesis, Nitrates - blood, Lipopolysaccharides - pharmacology, Intestinal Mucosa - metabolism, Lactic Acid - blood, Heart Rate - drug effects, Shock, Septic - physiopathology, Dobutamine - pharmacology, Coronary Circulation - drug effects

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750