Downstream effects of splanchnic ischemia-reperfusion injury on renal function and eicosanoid release

Abstract

This study examines the hypothesis that intestinal ischemia-reperfusion (I/R) injury contributes to renal dysfunction by altered renal eicosanoid release. Anesthetized Sprague-Dawley rats underwent 60 min of sham or superior mesenteric artery (SMA) occlusion with 60 min of reperfusion. The I/R groups received either allopurinol, pentoxifylline, 1-benzylimidazole, or carrier before SMA occlusion. In vivo renal artery blood flow was measured by Transonic flow probes, the kidneys were then perfused in vitro for 30 min, and the effluent was analyzed for eicosanoid release and renal function. Intestinal I/R caused a twofold increase in the ratio of renal release of thromboxane B2 to prostaglandin E2 and to 6-ketoprostaglandin F1alpha compared with the sham level, with a corresponding 25% decrease in renal sodium and inulin clearance and renal blood flow. Pentoxifylline or allopurinol pretreatment restored renal eicosanoid release and renal sodium and inulin clearance to the sham level but did not alter renal blood flow. Pretreatment with 1-benzylimidazole restored renal function, eicosanoid release, and renal blood flow to sham levels. These data suggest that severe intestinal I/R contributes to the downregulation of renal function. The decrease in renal function is due in part to toxic oxygen metabolites, which occur in the milieu of altered renal eicosanoid release, reflecting a decrease in vasodilator and an increase in vasoconstrictor eicosanoids.

The protective effects of curcumin on intestine and remote organs against mesenteric ischemia/reperfusion injury

“…Renal injuries induced by mesenteric I/R injury have also been reported (24), but the kidney was the less-affected organ in this study and had the lowest score of histopathological damage.…”

Acute mesenteric ischemia after cardio-pulmonary bypass surgery

“…Finally, damage to the intestinal micro-vessels and the disruption of the intestinal mucosal barrier results in leakage of water and bacteria, with resulting endotoxemia [23] and bacteremia [24,25] . Ultimately, multi-organ failure ensues and involves the liver [18] , heart [26] , kidneys [27] and lungs [28] . Acute pulmonary edema resulting from mesenteric ischemia/reperfusion is caused by an increase in pulmonary microvascular permeability to fluids and proteins, as well as smooth muscle dysfunction [29,30] .…”

Alteration of Mrp2 and P-gp expression, including expression in remote organs, after intestinal ischemia-reperfusion

“…In the kidney, the most prominent changes are swelling of endothelial cells and destruction of mitochondrial cristae in endothelial cells of glomerular capillaries and epithelial tubular cells (Mutlu et al, 2002). Also, after intestinal I/R, blood urea nitrogen (BUN) has been shown to increase, (Yang et al, 2004) and inulin clearance decreases (Rothenbach et al, 1997). The intestine, liver and kidney are involved in the excretion of many different xenobiotics, toxins, and endogenous compounds.…”