Effects of Dopexamine on Lipid Peroxidation During Aortic Surgery in Pigs: Comparison with Dopamine
ABSTRACT We investigated the dose-related effect of dopexamine and dopamine on free radical production and lipid peroxidation estimated by MDA measurements in an ischaemia-reperfusion model of supraceliac aortic repair.
Prospective, randomized, blinded experimental study.
Twenty-five healthy pigs.
All experiments were performed under general endotracheal anaesthesia. Supraceliac aortic cross clamping was performed in all pigs. The pigs were randomly assigned into five groups (n=5 in each group) and received a continuous intravenous infusion of normal saline (CTL), dopamine 2 microg kg(-1)min(-1) (dopa 2), dopamine 8 microg kg(-1)min(-1) (dopa 8), dopexamine 2 microg kg(-1)min(-1) (dopex 2), dopexamine 8 microg kg(-1)min(-1) (dopex 8). Cardiac output, mean arterial pressure, arterial blood gas analysis and blood sampling for plasma MDA measurements (to reveal lipid peroxidation) were recorded after induction of anaesthesia (baseline), 60 and 120 min after cross-clamping of aorta (ischaemia phase), and 60 and 120 min after restoration of flow (reperfusion phase).
Dopexamine and dopamine at 8 microgkg(-1)min(-1) reduced MDA at 60 and 120 min after reperfusion.
Dopexamine seems superior to dopamine in reducing oxygen free radicals and subsequent lipid peroxidation during reperfusion after supraceliac aortic cross clamping in pigs.
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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