Archives of Orthopaedic and Trauma Surgery

, Volume 121, Issue 4, pp 219–222

Hypoxia-inducible factor-1 activation and cyclo-oxygenase-2 induction are early reperfusion-independent inflammatory events in hemorrhagic shock

  • C. Hierholzer
  • B. G. Harbrecht
  • T. R. Billiar
  • D. J. Tweardy
Clinical and experimental forum

DOI: 10.1007/s004020000211

Cite this article as:
Hierholzer, C., Harbrecht, B., Billiar, T. et al. Arch Orth Traum Surg (2001) 121: 219. doi:10.1007/s004020000211

Abstract

Hemorrhagic shock (HS) initiates an inflammatory response that includes increased expression of inducible nitric oxide synthase (iNOS) and production of prostaglandins. Induction of iNOS during the ischemic phase of HS may involve the activation of the hypoxia-inducible factor-1 (HIF-1). Increased expression of cyclo-oxygenase-2 (COX-2) during HS contributes to prostaglandin production. The aim of this study was to determine whether the ischemic phase of HS results in the activation of HIF-1 and the induction of COX-2. The lungs of rats subjected to HS demonstrated a twofold increase in HIF-1 activation (P < 0.01) and a 7.4-fold increase in expression of COX-2 mRNA (P < 0.01) compared with sham controls. The upregulation of iNOS and COX-2 during ischemia are two important early response genes that promote the inflammatory response and may contribute to organ damage through the rapid and exaggerated production of nitric oxide and prostaglandins.

Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • C. Hierholzer
    • 1
  • B. G. Harbrecht
    • 1
  • T. R. Billiar
    • 1
  • D. J. Tweardy
    • 2
  1. 1.Department of Surgery, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USAUS
  2. 2.Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, BCM 286, Room N1319, Houston TX 77030, USA e-mail: dtweardy@bcm.tmc.edu, Tel.: +1-713-7988918, Fax: +1-713-7988299US