Sustained nitric oxide production via L-arginine administration ameliorates effects of intestinal ischemia-reperfusion

Background. The role of nitric oxide in intestinal ischemia-reperfusion is unclear-some studies link it to the harmful effects of ischemia-reperfusion , while others report it to be protective. We propose that nitric oxide lev els diminish in the reperfusion period in conjunction with the onset of inc reased capillary permeability, The aim of this study is to determine the ef fect of supplementing nitric oxide synthase with its substrate, L-arginine, on development of local mucosal injury and systemic capillary leak. Materials and methods. Rats underwent 30 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. The vehicle groups received L-arg inine either intravenously (4 mg/kg/min) or into the intestinal lumen, The intravenous groups received L-arginine either before the ischemic event or after 30 min of reperfusion. Capillary leak in the gut and lung were measur ed, as were degree of mucosal injury and number of infiltrating neutrophils . Appropriate controls were performed. Results. Thirty minutes of mesenteric ischemia followed by 4 h of reperfusi on significantly increased gut and lung leak, neutrophil infiltration, and the severity of mucosal injury. L-Arginine given iv prior to ischemia inhib ited lung leak, mucosal injury, and neutrophil infiltration. When arginine was given during the reperfusion period, lung leak and neutrophil infiltrat ion but not mucosal injury were reduced. Intraluminal L-arginine reduced mu cosa injury, but had no effect on capillary leak. Conclusions. supplementation with L-arginine enhances NO production, result ing in reduced systemic endothelial dysfunction, This may act as a useful c linical adjunct in the management of trauma patients in preventing the deve lopment of ARDS and multiple organ failure.