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  • Title: Effects of intrarenal administration of the calcium antagonist nimodipine during porcine aortic occlusion-induced ischemia/reperfusion injury.
    Author: Fröba G, Bracht H, Hauser B, Chkhouta AB, Huber-Lang M, Rittirsch D, Brückner UB, Radermacher P, Schelzig H.
    Journal: Shock; 2008 Jun; 29(6):717-23. PubMed ID: 18091572.
    Abstract:
    Ca++ antagonists have been tested to improve I/R injury in the kidney, but their clinical use is limited due to their hypotensive properties. Therefore, we tested the hypothesis on whether infusing the Ca++ blocker nimodipine directly into the renal artery would reduce kidney cell apoptosis and thus improve organ function in a porcine model of suprarenal abdominal aortic cross-clamping. In a prospective, randomized, controlled, blinded study, anesthetized, mechanically ventilated, and instrumented pigs underwent 45 min of suprarenal aortic cross-clamping animals receiving either 0.25 microg kg(-1) min(-1) nimodipine (n = 8) or vehicle (n = 8). Systemic and right kidney hemodynamics, oxygen exchange, and metabolism were assessed before clamping, as well as before and at 75 and 195 min of reperfusion (i.e., at 120 and 240 min after aortic occlusion). At the end of the experiments, the right kidney was harvested for conventional hematoxylineosin staining and immunohistochemistry for the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) gene expression and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin end labeling test). Neither systemic nor renal hemodynamics and oxygen exchange, plasma and urine protein concentrations, urine osmolarity, and lactate-pyruvate ratios showed any intergroup difference. Nimodipine infusion resulted in a significantly higher creatinine clearance after 195 min of reperfusion (26 [17 - 42] vs. 17 [9 - 22] mL x min(-1)) and attenuated renal tubular damage, as indicated by lower urinary small protein (25 kd) concentrations. Improved renal function was concomitant with significantly less pronounced positive nuclear terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin end labeling staining. In a porcine model of suprarenal aortic cross-clamping, intrarenal nimodipine infusion improved postischemia kidney function, most likely as a result of attenuated glomerular apoptosis.
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