Karabulut R, Sönmez K, Sancak B, Türkyilmaz Z, Demiroğullari B, Ozen I O, Ekingen G, Candan S, Başaklar A C, Kale N
Department of Pediatric Surgery, Faculty of Medicine, Gazy University, Ankara, Turkey.
Urol Res. 2002 Jul;30(3):164-8. doi: 10.1007/s00240-002-0256-3. Epub 2002 Jun 4.
Renal ischemia/reperfusion injury could arise as a consequence of clinical conditions such as renal transplantation, shock, cardiac arrest, hemorrhage and renal artery surgery. In this experimental study, we aimed to determine the preventive effects of amrinone on bilateral renal ischemia/reperfusion injury in rats. A total of 60 Wistar-albino rats were divided into six groups ( n=10). Midline laparotomies were made under ketamine anesthesia. In the sham, amrinone1 and amrinone2 without ischemia (AWI1 and AWI2) groups saline, 5 and 10 mg/kg of amrinone was infused, respectively. In the ischemia, ischemia plus amrinone1 (IPA1) and ischemia plus amrinone2 (IPA2) groups, saline and 5 and 10 mg/kg of amrinone was infused, respectively, at the beginning of reperfusion, subsequent to 45 min of bilateral renal artery occlusion. Following 6 h of reperfusion, blood was drawn to study serum BUN and creatinine and a bilateral nephrectomy was done to determine tissue malonyldialdehyde ( MDA) and myeloperoxidase (MPO) levels. The results were analysed by Mann-Whitney U-test. The parameters studied were statistically higher in the ischemia group compared with the other groups ( P<0.05 for each comparison), indicating renal I/R injury. These parameters were lower in the amrinone without ischemia groups (AWI1 and AWI2) than in the sham group, however there were no significant differences between the groups ( P>0.05, for each comparison). The treatment groups IPA1 and IPA2 had statistically similar results compared with the sham group, showing the preventive effect of amrinone on renal I/R injury at the given doses. We conclude that amrinone prevented experimental renal ischemia/reperfusion injury in rats, independently of the administered doses. This preventive effect of the agent could depend on its effect of regulating the microcirculation, in decreasing intracellular calcium and in preventing neutrophil activation. We propose that this preventive effect of amrinone - which has gained clinical application especially in cases of cardiac insufficiency - could also be exploited in clinical conditions related with renal ischemia/reperfusion.
肾缺血/再灌注损伤可能由肾移植、休克、心脏骤停、出血及肾动脉手术等临床情况引起。在本实验研究中,我们旨在确定氨力农对大鼠双侧肾缺血/再灌注损伤的预防作用。将60只Wistar白化大鼠分为6组(每组n = 10)。在氯胺酮麻醉下进行中线剖腹术。在假手术组、未缺血氨力农1组(AWI1)和未缺血氨力农2组(AWI2)中,分别输注生理盐水、5mg/kg和10mg/kg氨力农。在缺血组、缺血加氨力农1组(IPA1)和缺血加氨力农2组(IPA2)中,在双侧肾动脉阻断45分钟后再灌注开始时,分别输注生理盐水、5mg/kg和10mg/kg氨力农。再灌注6小时后,取血检测血清尿素氮和肌酐,并进行双侧肾切除术以测定组织丙二醛(MDA)和髓过氧化物酶(MPO)水平。结果采用Mann-Whitney U检验进行分析。与其他组相比,缺血组研究的参数在统计学上更高(每次比较P<0.05),表明存在肾缺血/再灌注损伤。未缺血氨力农组(AWI1和AWI2)的这些参数低于假手术组,但各组之间无显著差异(每次比较P>0.05)。治疗组IPA1和IPA2与假手术组相比在统计学上结果相似,表明氨力农在给定剂量下对肾缺血/再灌注损伤有预防作用。我们得出结论,氨力农可预防大鼠实验性肾缺血/再灌注损伤,与给药剂量无关。该药物的这种预防作用可能取决于其调节微循环、降低细胞内钙及预防中性粒细胞活化的作用。我们提出,氨力农的这种预防作用——尤其在心力衰竭病例中已获得临床应用——也可应用于与肾缺血/再灌注相关的临床情况。