Fröba Gebhard, Bracht Hendrik, Hauser Balázs, Chkhouta Archil B, Huber-Lang Markus, Rittirsch Daniel, Brückner Uwe B, Radermacher Peter, Schelzig Hubert
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.
Shock. 2008 Jun;29(6):717-23. doi: 10.1097/shk.0b013e318160d6f9.
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.
钙通道拮抗剂已被用于测试改善肾脏缺血再灌注损伤，但因其具有降压特性，临床应用受限。因此，我们测试了以下假设：在猪的肾上腹主动脉交叉钳夹模型中，将钙通道阻滞剂尼莫地平直接注入肾动脉是否会减少肾细胞凋亡，从而改善器官功能。在一项前瞻性、随机、对照、双盲研究中，对麻醉、机械通气并安装仪器的猪进行45分钟的肾上主动脉交叉钳夹，动物分为两组，分别接受0.25微克·千克⁻¹·分钟⁻¹的尼莫地平（n = 8）或赋形剂（n = 8）。在钳夹前以及再灌注75分钟和195分钟（即主动脉阻断后120分钟和240分钟）之前和之时，评估全身和右肾血流动力学、氧交换和代谢情况。实验结束时，取右肾进行常规苏木精-伊红染色以及免疫组化，检测细胞周期蛋白依赖性激酶抑制剂p21（WAF1/CIP1）基因表达和凋亡情况（末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸生物素末端标记试验）。全身和肾血流动力学、氧交换、血浆和尿蛋白浓度、尿渗透压以及乳酸-丙酮酸比值在两组间均无差异。尼莫地平输注导致再灌注195分钟后肌酐清除率显著更高（26 [17 - 42] 对 17 [9 - 22] 毫升·分钟⁻¹），并减轻了肾小管损伤，表现为尿中小分子蛋白（25 kd）浓度降低。肾功能改善伴随着核末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸生物素末端标记染色阳性程度显著减轻。在猪的肾上主动脉交叉钳夹模型中，肾内输注尼莫地平改善了缺血后肾功能，最可能的原因是肾小球凋亡减轻。
