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Effect of dopexamine on intestinal tissue concentrations of high-energy phosphates and intestinal release of purine compounds in endotoxemic rats

Objectives To determine the effect of dopexamine, a synthetic catecholamine ligand for dopaminergic and &bgr;2-adrenergic receptors, on intestinal release of adenosine 5′-triphosphate (ATP) degradation products and on intestinal tissue concentrations of high-energy phosphates during endotoxemia. Design Randomized, controlled trial. Setting Experimental laboratory. Subjects Twenty-one male Wistar rats. Interventions Rats given endotoxin (Escherichia coli lipopolysaccharide [LPS]; 1.5 mg/kg iv over 60 mins) were treated with a continuous infusion of dopexamine (DPX; 2.5 &mgr;g/kg/min, n = 7, group LPS + DPX) or 0.9% saline (n = 7, group LPS) during a study period of 120 mins. Animals in the control group (n = 7) received a volume-equivalent infusion of 0.9% saline without endotoxin. Measurements and Main Results In all groups, arterial and portal venous concentrations of adenosine, hypoxanthine, and uric acid were measured at baseline and at 60 and 120 mins after the endotoxin challenge, and we calculated the portal venous/arterial concentration differences as an indicator of the intestinal release of the purine compounds. Furthermore, at the end of the study, the intestinal tissue concentrations of the high-energy phosphates ATP, adenosine 5′-diphosphate (ADP), adenosine 5′-monophosphate (AMP), creatine phosphate, and adenosine were determined, and we calculated the adenine nucleotide pool, the ATP/ADP and AMP/adenosine ratios, and the adenylate energy charge of the intestinal tissue. Endotoxemia decreases intestinal tissue ATP, ADP, AMP, and creatine phosphate concentrations, increases tissue adenosine content, and increases the release of hypoxanthine and uric acid from the intestinal tract. Dopexamine attenuates the endotoxin-induced decrease of the intestinal tissue adenine nucleotide pool, the AMP/adenosine ratio, and the release of the ATP-degradation products hypoxanthine and uric acid from the intestinal tract. Conclusions Normotensive endotoxemia is associated with a deterioration of the intestinal energy balance and an increased release of ATP degradation products, indicating intestinal tissue ischemia. Furthermore, these results suggest the beneficial effects of dopexamine on pathophysiologic alterations of the intestinal energy metabolism during endotoxemia.