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

Abstract

WHAT THIS PAPER ADDS Complications of juxtarenal aortic aneurysm repair include renal ischaemia reperfusion injury and post-operative colonic ischaemia. Renal ischaemia reperfusion injury results in the production of reactive oxygen species during oxidative stress. In the present study renal cooling preserved renal function. Above all, renal cooling was able to reduce the detrimental remote effects on sigmoid integrity of renal ischaemia reperfusion caused by suprarenal clamping; by preserving microcirculatory flow, attenuating circulating leukocyte ROS production, and decreasing leukocyte infiltration in the sigmoid. Objectives: 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. Methods: Open juxtarenal aortic aneurysm repair was simulated in 28 male Wistar rats with suprarenal cross clamping for 45 min, followed by 20 min 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. Results: Suprarenal cross clamping caused deterioration of all systemic parameters. Only cold renal perfusion protected against serum creatinine rise: 0.45 mg/dL without renal perfusion, 0.33 mg/dL, and 0.14 mg/dL (p ¼ .009) with warm and cold perfusion, respectively. Microcirculation in the sigmoid was attenuated with warm (p ¼ .002) and cold renal perfusion (p ¼ .002). A smaller increase of ROS production (p ¼ .034) was seen only after cold perfusion, while leukocyte infiltration in the sigmoid colon decreased after warm (p ¼ .006) and cold perfusion (p ¼ .018). Finally, digestive enzyme leakage increased more without (1.5AU) than with warm (1.3AU; p ¼ .007) and cold renal perfusion (1.2AU; p ¼ .002). Conclusions: 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.

Effect of Shorter Cross Clamp Time vs. longer Cross Clamp time on cardiac enzyme levels in pts of CAD undergoing CABG

“…3,4 Reduced ischemic damage: Cross clamp time can impact the amount of ischemic (lack of blood flow) damage that occurs to the tissues or organs supplied by the clamped artery. Shorter cross clamp time may result in less ischemic damage compared to longer clamp times, which can be particularly important in surgeries that involve major blood vessels or organs with high metabolic demands, such as the heart or brain 5,6,7,8 .…”

“…Lower risk of complications: Shorter cross clamp time may be associated with a lower risk of complications related to ischemic injury, such as tissue necrosis (cell death), organ dysfunction, or postoperative complications. For example, in cardiac surgery, shorter cross clamp time during coronary artery bypass graft (CABG) surgery has been associated with reduced risk of complications like myocardial injury and acute kidney injury 3,6,8 .…”

In Vitro/Ex Vivo Models for the Study of Ischemia Reperfusion Injury during Kidney Perfusion

“…Nevertheless, complications still exist, and current HMP technologies provide limited protection. For instance, HMP limits reactive oxygen species (ROS) production in the context of IR [5,6], but does so only partially [7]. As donor demography continues to evolve and further extension of inclusion criteria is expected, there is a clear need for improved preservation.…”