Protection by Pyruvate Infusion in a Rat Model of Severe Intestinal Ischemia-Reperfusion Injury

Abstract

Several lines of evidence suggest a strong protective potential of pyruvate against ischemia-reperfusion injury. Here, we studied the effect of pyruvate infusion on injury of the small intestine and on systemic parameters in a rat model of severe mesenteric ischemia-reperfusion injury. Mesenteric ischemia-reperfusion was induced by occlusion/reopening of the superior mesenteric artery of male Wistar rats (90 min ischemia, 120 min reperfusion). Sodium pyruvate was infused at overall doses of 50, 250, and 1,000 mg/kg during two time windows: 30 min before until the induction of ischemia and 30 min before reperfusion until 60 min after beginning of reperfusion. Pyruvate infusion attenuated ischemia-reperfusion injury of the small intestine between 25% and 55% as indicated by macroscopic and microscopic evaluation, intestinal hemorrhages, and myeloperoxidase activity (neutrophil invasion). There were no significant differences in the local protective effects exerted by the three doses of sodium pyruvate applied. At 250 mg sodium pyruvate/kg and 1,000 mg sodium pyruvate/kg, however, blood pH values were less acidotic, and at 250 mg sodium pyruvate/kg the mean arterial blood pressure remained at higher values during the reperfusion phase. A significant increase in the blood plasma sodium concentration only occurred at 1,000 mg sodium pyruvate/kg. Pyruvate infusion clearly protects the small intestine against ischemia-reperfusion injury. Protection can already be achieved at doses where sodium overload is negligible. Protection primarily results from local effects on the small intestine. Only at a dose of 250 mg sodium pyruvate/kg and above, systemic effects may additionally contribute.