NDT Advance Access originally published online on April 9, 2008
Nephrology Dialysis Transplantation 2008 23(7):2213-2222; doi:10.1093/ndt/gfn093
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Application of normobaric hyperoxia therapy for amelioration of haemorrhagic shock-induced acute renal failure*
1 Division of Nephrology, Assaf Harofeh Medical Center, Zerifin 70300, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel 2 Research & Development Unit, Assaf Harofeh Medical Center, Zerifin 70300, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel
Correspondence and offprint requests to: Shai Efrati, Head of the Research & Development Unit, Assaf Harofeh Medical Center, Zerifin 70300, Israel. Tel: +972-8-9778411; Fax: +972-8-9779748; E-mail: efratishai{at}013.net
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Abstract |
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Background. Hypoxia resultant from haemorrhagic shock is the primary cause of kidney damage. Application of normobaric hyperoxia therapy (NHT) is an acceptable treatment for acute haemorrhagic shock. We investigated the effect of NHT on amelioration of haemorrhagic shock-induced rat renal failure.
Methods. Twenty-four Sprague-Dawley rats were subjected to gradual blood withdrawal/reperfusion, followed by 12-h, 24-h or 48-h NHT. Verification/monitoring of intrarenal hypoxia was performed using Hypoxyprobe-TM-1. Subsequently, cystatin C, urea and creatinine were assessed in serum by a Hitachi autoanalyser, and NO, 3-nitro-tyrosine, STAT-8-isoprostane and NF-kB in renal medullae and cortices by specific ELISAs.
Results. In rats subjected to haemorrhagic shock, 12- to 48-h NHT significantly reduced intrarenal Hypoxyprobe-TM-1 stained areas and attenuated augmentation of urea, creatinine and cystatin C. Haemorrhagic shock resulted in a 10-fold drop of intrarenal NO availability. 12-h and 24-h, but not 48-h, NHT significantly increased cortical/medullar NO synthesis, the latter, however, not approaching the pre-shock values. Significant shock-induced accumulation of STAT-8-isoprostane and 3-nitro-tyrosine was further exacerbated by NHT. Haemorrhagic shock activated NF-kB in ischaemic tissues, which was not attenuated by NHT.
Conclusions. (1) 12- to 48-h NHT decreased intrarenal hypoxia signs and ameliorated deterioration of renal functions in a rat model of haemorrhagic shock-induced renal failure. (2) 12- to 24 h NHT improved bioavailability of NO in cortices/medullae of kidneys recuperating from haemorrhagic shock. (3) If any anti-inflammatory activities were stimulated by NHT, they would not be mediated via the NF-kB pathway. (4) Despite NHT-associated elevation of reactive oxygen species (ROS), early oxygen supply proved mandatory for effective recuperation of ischaemic kidney from detrimental consequences of haemorrhagic shock.
Keywords: acute renal failure; haemorrhagic shock; ischaemia-reperfusion; normobaric hyperoxia; oxidative stress
* This manuscript includes data obtained as a part of Mr Ben-Aharon's MSci project performed for Tel-Aviv State University, on the premises of Research & Development Unit, Assaf Harofeh Medical Center, Zerifin, Israel.
Received for publication: 20. 7.07
Accepted in revised form: 30. 1.08