Experimental study of the effect of adrenaline tolerance on intestinal ischaemia–reperfusion

Abstract
Background: Adrenaline tolerance improves survival in animal models of shock. The purpose of this study was to determine the effects of adrenaline tolerance on intestinal ischaemia–reperfusion in a mouse model. Methods: Adrenaline tolerance was developed by injecting intravenous adrenaline, gradually increasing the dose to 2 mg/kg over 5 days. In experimental animals the superior mesenteric artery was clamped for 120 min and then released. Evans blue dye was given intravenously to all animals to quantify pulmonary microvascular injury. Some 60 min after clamp release, the animals were killed and the effects of reperfusion assessed on tissue samples. Results: Evans blue dye concentrations were significantly higher in animals with intestinal ischaemia–reperfusion than in those having sham intestinal ischaemia–reperfusion or in adrenaline-tolerant mice having intestinal ischaemia–reperfusion or sham ischaemia–reperfusion (P<0·01). Malonyldialdehyde levels increased significantly in the lung in the intestinal ischaemia–reperfusion group compared with those in the sham ischaemia–reperfusion group (P<0·001 for liver, lung and small intestine), whereas there was no difference in adrenaline-tolerant animals. There was no significant change induced by adrenaline tolerance in myeloperoxidase levels in any organ. Conclusion: Adrenaline tolerance reduced the lung permeability caused by intestinal ischaemia–reperfusion. Catecholamines may play a role in free radical generation induced by ischaemia–reperfusion.