Cold Renal Perfusion During Simulation of Juxtarenal Aortic Aneurysm Repair Reduces Systemic Oxidative Stress and Sigmoid Damage in Rats

Abstract

Juxtarenal aortic surgery induces renal ischaemia reperfusion, which contributes to systemic inflammatory tissue injury and remote organ damage. Renal cooling during suprarenal cross clamping has been shown to reduce renal damage. It is hypothesised that renal cooling during suprarenal cross clamping also has systemic effects and could decrease damage to other organs, like the sigmoid colon. Open juxtarenal aortic aneurysm repair was simulated in 28 male Wistar rats with suprarenal cross clamping for 45min, followed by 20min of infrarenal aortic clamping. Four groups were created: sham, no, warm (37°C saline), and cold (4°C saline) renal perfusion during suprarenal cross clamping. Primary outcomes were renal damage and sigmoid damage. To assess renal damage, procedure completion serum creatinine rises were measured. Peri-operative microcirculatory flow ratios were determined in the sigmoid using laser Doppler flux. Semi-quantitative immunofluorescence microscopy was used to measure alterations in systemic inflammation parameters, including reactive oxygen species (ROS) production in circulating leukocytes and leukocyte infiltration in the sigmoid. Sigmoid damage was assessed using digestive enzyme (intestinal fatty acid binding protein - I-FABP) leakage, a marker of intestinal integrity. Suprarenal cross clamping caused deterioration of all systemic parameters. Only cold renal perfusion protected against serum creatinine rise: 0.45mg/dL without renal perfusion, 0.33mg/dL, and 0.14mg/dL (p=.009) with warm and cold perfusion, respectively. Microcirculation in the sigmoid was attenuated with warm (p=.002) and cold renal perfusion (p=.002). A smaller increase of ROS production (p=.034) was seen only after cold perfusion, while leukocyte infiltration in the sigmoid colon decreased after warm (p=.006) and cold perfusion (p=.018). Finally, digestive enzyme leakage increased more without (1.5AU) than with warm (1.3AU; p=.007) and cold renal perfusion (1.2AU; p=.002). Renal ischaemia/reperfusion injury after suprarenal cross clamping decreased microcirculatory flow, increased systemic ROS production, leukocyte infiltration, and I-FABP leakage in the sigmoid colon. Cold renal perfusion was superior to warm perfusion and reduced renal damage and had beneficial systemic effects, reducing sigmoid damage in this experimental study.