Effect of milrinone on ischemia-reperfusion injury in the rat kidney

T. Nishiki, H. Kitada, Y. Okabe, Y. Miura, K. Kurihara, S. Kawanami, M. Tanaka

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Abstract

Background: Milrinone (MIL), a phosphodiesterase (PDE) 3 inhibitor, exhibits cardiotonic and angioectatic effects. Various PDE inhibitors have been shown to suppress inflammatory cytokines. In this study, we evaluated the angioectatic and anti-inflammatory cytokine effects of MIL on renal function after warm ischemia in a rat ischemia-reperfusion (I-R) injury model. Materials and methods: MIL or control solution was perfused from the left renal artery to the right kidney, and the left kidney was excised. The right renal artery, vein, and ureter were clamped and then released after 50 minutes to produce warm ischemia. We evaluated control (n = 7), MIL (n = 7), and sham operation (n = 7) groups for serum creatinine, blood urea nitrogen (BUN), blood flow, expression of tumor necrosis factor (TNF)-α mRNA, apoptosis index, and histological evidence of acute tubular necrosis. Results: Serum creatinine and BUN concentrations peaked at 24 hours after reperfusion. MIL treatment significantly reduced serum creatinine (control group 1.27 ± 0.45 mg/dL vs MIL group 0.77 ± 0.19 mg/dL, P < .05; sham 0.35 ± 0.2 mg/dL) and BUN (control 67.6 ± 13.6 mg/dL vs MIL 51.0 ± 8.8 mg/dL, P < .05; sham 23.0 ± 4.2 mg/dL) levels at 24 hours. Thereafter, serum creatinine and BUN concentrations in the MIL group remained significantly lower compared with the control group for 120 hours (P < .05). MIL group exhibited significantly higher tissue blood flow, less acute tubular necrosis, lower expression of TNF-α mRNA in renal tissue, and lower apoptotic index (P < .05). Conclusions: MIL maintained renal tissue blood flow by its vasodilatory effect, suppressed expression of TNF-α mRNA by increasing intracellular cyclic adenosine monophosphate, and ultimately decreased tubular cell apoptosis, thus protecting renal function after warm I-R injury.

Original languageEnglish
Pages (from-to)1489-1494
Number of pages6
JournalTransplantation Proceedings
Volume43
Issue number5
DOIs
Publication statusPublished - Jun 1 2011

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

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    Nishiki, T., Kitada, H., Okabe, Y., Miura, Y., Kurihara, K., Kawanami, S., & Tanaka, M. (2011). Effect of milrinone on ischemia-reperfusion injury in the rat kidney. Transplantation Proceedings, 43(5), 1489-1494. https://doi.org/10.1016/j.transproceed.2011.03.009