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Am J Physiol Renal Physiol 293: F713-F722, 2007. First published June 27, 2007; doi:10.1152/ajprenal.00161.2007
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Isoflurane protects against renal ischemia and reperfusion injury and modulates leukocyte infiltration in mice

H. Thomas Lee,1 Mihwa Kim,1 Minjae Kim,1 NaLa Kim,1 Frederic T. Billings, IV,1 Vivette D. D'Agati,2 and Charles W. Emala, Sr.1

1Department of Anesthesiology and 2Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York

Submitted 7 April 2007 ; accepted in final form 25 June 2007

Inflammation after renal ischemia-reperfusion (IR) injury is a major contributor to renal cell death. We previously demonstrated that several volatile anesthetics protect against renal IR injury and necrosis in rats in vivo. We subsequently showed that volatile anesthetics produced direct anti-inflammatory and anti-necrotic effects in cultured proximal tubule cells in vitro. In this study, we wanted to determine whether the volatile anesthetic isoflurane protects against renal IR injury by producing anti-inflammatory effects in mice. C57BL/6 mice subjected to renal IR under isoflurane anesthesia demonstrated improved renal function and reduced necrosis compared with mice subjected to renal IR under pentobarbital anesthesia. Mice subjected to renal IR under isoflurane anesthesia also showed a reduction in inflammation evidenced by a reduced renal influx of neutrophils and macrophages, reduced ICAM-1 expression, less upregulation of proinflammatory mRNAs (TNF-{alpha}, ICAM-1, KC, and IL-1beta) as well as reduced nuclear translocation of NF-{kappa}B 24 h after renal IR injury. Analysis of specific lymphocyte subset trafficking to the kidney using flow cytometry demonstrated that isoflurane anesthesia reduced intrarenal influx of CD3+, CD4+, CD8+, and NK1.1+ lymphocytes at 3 h after renal ischemia compared with pentobarbital anesthesia. However, only the differential reduction of NK1.1+ lymphocytes persisted 24 h after renal ischemia. Therefore, we conclude that isoflurane anesthesia significantly attenuated renal IR injury in mice by reducing inflammation and modulating leukocyte influx. In particular, neutrophil, macrophage, and NK1.1+ lymphocyte cell modulation may play a significant role in renal protection by isoflurane anesthesia.

acute renal failure; flow cytometry; immunohistochemistry; inflammation; volatile anesthetic



Address for reprint requests and other correspondence: H. Thomas Lee, Dept. of Anesthesiology, Anesthesiology Research Laboratories, Columbia Univ., P&S Box 46 (PH-5), 630 West 168th St., New York, NY 10032-3784 (e-mail: tl128{at}columbia.edu)




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Am. J. Physiol. Renal Physiol.Home page
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Sevoflurane protects against renal ischemia and reperfusion injury in mice via the transforming growth factor-{beta}1 pathway
Am J Physiol Renal Physiol, July 1, 2008; 295(1): F128 - F136.
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Am. J. Physiol. Renal Physiol.Home page
M. Kim, M. Kim, N. Kim, V. D. D'Agati, C. W. Emala Sr, and H. T. Lee
Isoflurane mediates protection from renal ischemia-reperfusion injury via sphingosine kinase and sphingosine-1-phosphate-dependent pathways
Am J Physiol Renal Physiol, December 1, 2007; 293(6): F1827 - F1835.
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