[Show abstract][Hide abstract] ABSTRACT:
INTRODUCTION: The effects of dopexamine, a beta2-agonist, on peri-operative and sepsis related haemodynamic, microvascular, immune and organ dysfunction are controversial and poorly understood. We investigated these effects in a rodent model of laparotomy and endotoxaemia. METHODS: In two experiments, 80 male Wistar rats underwent laparotomy. In 64 rats this was followed by administration of endotoxin, the remainder (16) underwent sham endotoxaemia. Endotoxaemic animals received either dopexamine at 0.5, 1 or 2 ug kg-1 min-1 or 0.9% saline vehicle (controls) as resuscitation fluid. The effects of dopexamine on global haemodynamics, mesenteric regional microvascular flow, renal and hepatic function and immune activation were evaluated. RESULTS: Endotoxin administration was associated with a systemic inflammatory response (increased plasma levels of TNF-alpha, IL-1beta, IL-6 and IL-10 as well as cell adhesion molecules CD11a and CD11b), increased pulmonary MPO activity (indicating pulmonary leucocyte infiltration) whilst biochemical changes demonstrated lactic acidosis with significant renal and hepatic injury. Dopexamine administration was associated with less severe lactic acidosis (pooled dopexamine vs controls - [lactate] (mmol l-1): 2.2 +/- 0.2 vs 4.0 +/- 0.5, p<0.001) and reductions in the systemic inflammatory response (pooled dopexamine vs control - 4 hour [TNF-alpha] (pg ml-1): 324 +/- 93 vs 97 +/- 14, p<0.01), pulmonary myeloperoxidase (MPO) activity and hepatic and renal injury (pooled dopexamine vs control - [ALT] (IU l-1): 81 +/- 4 vs 138 +/- 25, p<0.05; [Creatinine] (mumol l-1): 49.4 +/- 3.9 vs 76.2 +/- 9.8, p<0.005). However, in this study, clinically relevant doses of dopexamine were not associated with clinically significant changes in MAP, CI or gut regional microvascular flow. CONCLUSIONS: In this model dopexamine can attenuate the systemic inflammatory response, reduce tissue leucocyte infiltration and protect against organ injury at doses that do not alter global haemodynamics or regional microvascular flow. These findings suggest that immunomodulatory effects of catecholamines may be clinically significant when used in critically ill surgical patients and are independent of their haemodynamic actions.
Critical care (London, England) 03/2013; 17(2):R57. DOI:10.1186/cc12585
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