J Gu1, J Chen, P Xia, G Tao, H Zhao, D Ma. 1. Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing, China.
Abstract
BACKGROUND: Renal ischemia-reperfusion (I/R) may cause acute lung injury (ALI). The mortality of combined acute kidney injury and ALI is extremely high. Dexmedetomidine, an α(2) adrenergic agonist, exerts potent anti-inflammatory and organoprotective effects in addition to its sedative and analgesic properties. We sought to elucidate whether dexmedetomidine can attenuate lung injury following renal I/R in a murine model of renal I/R. METHODS: Adult C57BL/6J male mice were randomized to five groups: sham-operated control (Sham); renal I/R (I/R); intraperitoneal injection of dexmedetomidine 25 μg/kg before ischemia (pre-dex) and after perfusion (post-dex); combination of α(2) adrenergic antagonist atipamezole 250 μg/kg prior to dexmedetomidine pre-treatment (atip-dex). Kidney I/R was induced by bilateral renal pedicle clamping for 45 min and followed by 6 h reperfusion. The pulmonary tissues were harvested for histopathological evaluation, wet/dry ratio measurement, biochemical analysis of myeloperoxidase (MPO), Polymerase chain reaction (PCR) determination of Inter-cellular adhesion molecule (ICAM-1) and Tumor necrosis factor - alpha (TNF-α) mRNA. RESULTS: Renal IR induced significant pulmonary injuries, increased wet/dry ratio together with the enhanced of MPO activities and increased ICAM-1 and TNF-α mRNA level. Both pre- and post-treatment with dexmedetomidine markedly reduced lung edema and inflammatory response and lowered MPO activity and ICAM-1 and TNF-α mRNA expression. The protective effects of dexmedetomidine in the lung were partially reversed by atipamezole, but there were no effect on ICAM-1 and TNF-α mRNA expression level. CONCLUSIONS: Dexmedetomidine is capable of attenuating remote lung injury induced by renal IR via both α(2) adrenoceptors dependent and independent mechanisms.
BACKGROUND:Renal ischemia-reperfusion (I/R) may cause acute lung injury (ALI). The mortality of combined acute kidney injury and ALI is extremely high. Dexmedetomidine, an α(2) adrenergic agonist, exerts potent anti-inflammatory and organoprotective effects in addition to its sedative and analgesic properties. We sought to elucidate whether dexmedetomidine can attenuate lung injury following renal I/R in a murine model of renal I/R. METHODS: Adult C57BL/6J male mice were randomized to five groups: sham-operated control (Sham); renal I/R (I/R); intraperitoneal injection of dexmedetomidine 25 μg/kg before ischemia (pre-dex) and after perfusion (post-dex); combination of α(2) adrenergic antagonist atipamezole 250 μg/kg prior to dexmedetomidine pre-treatment (atip-dex). Kidney I/R was induced by bilateral renal pedicle clamping for 45 min and followed by 6 h reperfusion. The pulmonary tissues were harvested for histopathological evaluation, wet/dry ratio measurement, biochemical analysis of myeloperoxidase (MPO), Polymerase chain reaction (PCR) determination of Inter-cellular adhesion molecule (ICAM-1) and Tumor necrosis factor - alpha (TNF-α) mRNA. RESULTS: Renal IR induced significant pulmonary injuries, increased wet/dry ratio together with the enhanced of MPO activities and increased ICAM-1 and TNF-α mRNA level. Both pre- and post-treatment with dexmedetomidine markedly reduced lung edema and inflammatory response and lowered MPO activity and ICAM-1 and TNF-α mRNA expression. The protective effects of dexmedetomidine in the lung were partially reversed by atipamezole, but there were no effect on ICAM-1 and TNF-α mRNA expression level. CONCLUSIONS:Dexmedetomidine is capable of attenuating remote lung injury induced by renal IR via both α(2) adrenoceptors dependent and independent mechanisms.
Authors: Serdar Kuru; Osman Bahadir Bozkirli; Aziz Mutlu Barlas; Mehmet Esat Duymus; Mehmet Senes; Nihat Yumusak; Cevdet Yilmaz; Kemal Kismet Journal: Int Surg Date: 2015-01