Resuscitation from traumatic hemorrhagic shock with Na+/H+ exchanger inhibitor

D. Wu, H. Dai, J. Arias, L. Latta, W. M. Abraham

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Severe hemorrhage from traumatic injury is a major causative factor in almost half of these deaths on the battlefield, especially during the early period (<2h) after injury. Intervention with low-volume fluid resuscitation is increasingly preferred than more aggressive fluid replacement. We evaluated the use of a Na+/H+ exchanger (NHE) inhibitor, as a cardioprotective adjunct therapy to low-volume resuscitation in a rat model of traumatic hemorrhagic shock. Methods: Femur fracture with soft tissue injury was induced in 28 anesthetized male rats. The animals were then bled via the carotid artery to maintain a mean arterial pressure of 40 mmHg for 20 minutes. Groups: 1) no therapy; 2) 15 ml/kg Hextend infusion over 40 minutes; 3) 3 mg/kg BIIB513 (NHE-1 inhibitor) + 15 ml/kg Hextend infusion over 40 minutes. After 4 hours, the animals who survived received a second infusion of Hextend. The experiment was terminated at 6 hours after initial resuscitation. Data are reported as mean ± SD. Results: All animals in the no therapy group died within 2 hours. Compared to Hextend infusion alone, the addition of NHE-1 inhibition with BIIB513, improved the hemodynamic response to fluid resuscitation (Fig 1), increased blood oxygen content, prevented metabolic acidosis, and improved 6 hour survival (42% in Hextend group vs 80% in BIIB513 + Hextend group). NHE-1 inhibition also resulted in reduced plasma levels of TNF-α, ICAM-1 and C-reactive protein, and attenuated neutrophil infiltration in the liver. Conclusion: NHE-1 inhibition with BIIB513 improved the hemodynamic response to fluid resuscitation, attenuated tissue inflammatory mediators, and most importantly improved survival.

Original languageEnglish (US)
Title of host publication25th Southern Biomedical Engineering Conference 2009
Pages307-308
Number of pages2
DOIs
StatePublished - Nov 6 2009
Event25th Southern Biomedical Engineering Conference 2009 - Miami, FL, United States
Duration: May 15 2009May 17 2009

Publication series

NameIFMBE Proceedings
Volume24
ISSN (Print)1680-0737

Other

Other25th Southern Biomedical Engineering Conference 2009
CountryUnited States
CityMiami, FL
Period5/15/095/17/09

    Fingerprint

Keywords

  • Metabolic acidosis
  • Organ function
  • Proinflammatory mediator
  • Traumatic hemorrhagic shock

ASJC Scopus subject areas

  • Biomedical Engineering
  • Bioengineering

Cite this

Wu, D., Dai, H., Arias, J., Latta, L., & Abraham, W. M. (2009). Resuscitation from traumatic hemorrhagic shock with Na+/H+ exchanger inhibitor. In 25th Southern Biomedical Engineering Conference 2009 (pp. 307-308). (IFMBE Proceedings; Vol. 24). https://doi.org/10.1007/978-3-642-01697-4_108