Der renale Ischämie- und Reperfusionsschaden beim suprarenalen Aortenclamping im Großtiermodell unter Einfluss des Kalzium-Kanal-Blockers Nimodipin

Abstract

Juxtarenal crossclamping is associated with acute, temporary, interruption of renal blood flow, which may lead to acute renal failure requiring haemodialysis in up to 50% of patients. Ischemia reperfusion (I/R) is thought to play a major role in the pathogenesis of acute renal failure after juxtarenal cross-clamping. The protective effect of the calcium channel blocker (CCB) nimodipine in I/R models has already been shown. The down regulation of the cytosol and mitochondrial calcium levels seems to be a factor in prevention of I/R injury. Up to now, only I/R models are presented with systemic application of CCB. A better result in histomorphological and renal function post ischaemia are known. However in animal experiments, side effects of CCB´s on the systemic hemodynamic are described. We carried out selective perfusion during cross-clamping into the renal artery in our I/R model with pics, to reduce the side effects and rise the local dose. 16 anaesthetised and mechanically ventilated pigs were instrumented to measure systemic and renal hemodynamics, oxygen exchange and metabolism. During 45 minutes of juxtarenal aortic crossclamping animals received nimodipine or NaCl placed into the right renal artery via a catheter. 195 minutes after declamping and several measurements, the pigs were killed and the kidneys stored for histological examinations. The creatinine clearance (p=0.02) and the urine flow (p<0.05) after treatment was found in the nimodipine group to be significantly higher with equal urine osmolality.The terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (Tunel)-test shows the count of apoptotic cells in the renal tissue and is a one marker for cell damage. There was significantly less apoptosis in the nimodipine group(p=0.03). Conclusion: Intra arterial administration of nimodipine during cross-clamping of the suprarenal aorta decreases the renal cell damage and increases the renal function in comparison with the control group.