Increased severity of renal ischemia-reperfusion injury with venous clamping compared to arterial clamping in a rat model

Abstract

Arterial inflow occlusion is a well-known mechanism of renal injury during major vascular surgery. In contrast, renal injury from venous outflow obstruction is poorly understood. The goal of this study was to examine the injury pattern of renal venous outflow obstruction, compare this with the traditional model of arterial occlusion, and examine possible mechanisms. Male Fisher rats were used for the renal warm ischemia model. Twenty-five minutes of renal ischemia was induced by selectively occluding either the renal artery or vein. After 24 h of reperfusion, whole blood and kidney tissue were collected for further analysis. Serum creatinine (SCr) concentrations taken 24 h after reperfusion were significantly greater in the venous occlusion group (V) when compared to the arterial group (A). While histology did not demonstrate significant differences in extent of necrosis between both groups, a stronger inflammatory response resulted from venous occlusion. Specifically, significantly greater MCP-1 mRNA and significantly greater MCP-1, TNF-alpha, and HO-1 protein levels were found in the venous group, while no differences in MIP-2, ICAM-1, and VCAM-1 mRNA expression existed between A and V. Further analysis demonstrated presence of increased cleaved caspase-3 protein in the artery group than in the venous group. Venous renal outflow obstruction results in more severe functional renal injury when compared to arterial inflow occlusion. Macrophage activation and neutrophilic infiltration appear to be exaggerated during venous occlusion.