Faddegon Stephen, Best Sara L, Olweny Ephrem O, Tan Yung K, Park Samuel K, Mir Saad A, Cadeddu Jeffrey A
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Can J Urol. 2012 Jun;19(3):6274-9.
Growing evidence suggests that phosphodiesterase-5 inhibitors may mitigate ischemia-related renal damage through multiple mechanisms. We evaluated the role of tadalafil in renal function preservation during experimentally induced ischemia/reperfusion injury (IRI) in a solitary kidney porcine model.
Ten adult female pigs underwent left laparoscopic nephrectomy followed by a 1 week recovery period. They were then randomized to tadalafil versus no treatment prior to cross-clamping the contralateral renal hilum for 90 minutes. The experimental group received 40 mg tadalafil in two equally divided doses, 12 hours before and just prior to surgery. Serum creatinine for each animal was obtained just prior to ischemia induction (D0) and at days 1, 3 and 7 following hilar occlusion. Median creatinine at each time point was compared between groups using the Kruskal-Wallis test.
Median serum creatinine at D0 was significantly lower in the tadalafil group (after two doses of tadalafil) (123.8 µmol/L versus 168.0 µmol/L, p = 0.009). As expected, median creatinine for each group rose significantly on D1 (p = 0.04 for each). Median creatinines following hilar occlusion at D1, D3 and D7, however, were not significantly different between groups.
In this porcine model, administration of perioperative tadalafil improves preoperative renal function, but it does not appear to mitigate ischemia/ reperfusion injury from hilar occlusion.
越来越多的证据表明，磷酸二酯酶-5抑制剂可能通过多种机制减轻缺血相关的肾损伤。我们评估了他达拉非在单肾猪模型实验性诱导缺血/再灌注损伤（IRI）期间对肾功能保护的作用。
10只成年雌性猪接受左侧腹腔镜肾切除术，随后恢复期为1周。然后在夹闭对侧肾蒂90分钟之前，将它们随机分为他达拉非组和未治疗组。实验组在手术前12小时和即将手术前分两次等量给予40mg他达拉非。在缺血诱导前（D0）以及肾蒂阻断后第1、3和7天获取每只动物的血清肌酐。使用Kruskal-Wallis检验比较两组在每个时间点的肌酐中位数。
他达拉非组（给予两剂他达拉非后）在D0时的血清肌酐中位数显著更低（123.8µmol/L对168.0µmol/L，p = 0.009）。正如预期的那样，每组的肌酐中位数在D1时显著升高（每组p = 0.04）。然而，在D1、D3和D7肾蒂阻断后的肌酐中位数在两组之间没有显著差异。
在这个猪模型中，围手术期给予他达拉非可改善术前肾功能，但似乎并不能减轻肾蒂阻断引起的缺血/再灌注损伤。
