Low-volume resuscitation from traumatic hemorrhagic shock with Na+/H+ exchanger inhibitor

Dongmei Wu, Hui Dai, Jaqueline Arias, Loren Latta, William M. Abraham

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Objective: To evaluate the use of a Na/H exchanger (NHE-1) inhibitor as a cardioprotective adjunct therapy to low-volume resuscitation in two different rat models of traumatic hemorrhagic shock. Design: Experimental, prospective study. Setting: Medical center research laboratory. Subjects: Sprague Dawley male rats. Interventions: Series 1: femur fracture was induced in anesthetized rats, followed by pressure-controlled hemorrhage (40 mm Hg for 20 minutes) and resuscitation. Groups: 1) no therapy; 2) 15 mL/kg hetastarch; and 3) 3 mg/kg benzamide, N-(aminoiminomethyl)-4-[4-(2-furanylcarbonyl)-1-piperazinyl]-3- (methylsulfonyl), methanesulfonate (BIIB513) (NHE-1 inhibitor) + 15 mL/kg hetastarch infusion over 40 minutes. The experiment was terminated at 6 hours after resuscitation. Series 2: the rats received laparotomy and closure under anesthesia and subsequently remained conscious for the rest of the study. The rats were subjected to volume-controlled hemorrhage (2.5 mL/100 g) followed by resuscitation as described in series 1. The experiment was terminated at 24 hours after resuscitation. Measurements and main results: Series 1: all animals in the no-therapy group died within 2 hours. Compared with hetastarch infusion alone, the addition of NHE-1 inhibitor improved the hemodynamic response to fluid resuscitation, increased blood oxygen content, prevented metabolic acidosis, and improved 6-hour survival (42% in hetastarch group vs. 80% in BIIB513 + hetastarch group). NHE-1 inhibition also resulted in reduced plasma levels of tumor necrosis factor-α, intercellular adhesion molecule-1, and C-reactive protein, and attenuated neutrophil infiltration in the liver. Series 2: all animals in the no-therapy group died within 4 hours after hemorrhage. Compared with hetastarch infusion alone, the addition of BIIB513 improved 24-hour survival (44% in hetastarch group vs. 78% in BIIB513 + hetastarch group). NHE-1 inhibition also reduced plasma levels alanine aminotransferase at 24 hours after resuscitation. Conclusions: NHE-1 inhibition facilitated the hemodynamic response to fluid resuscitation, attenuated tissue inflammatory injury, and organ dysfunction, but most importantly improved survival.

Original languageEnglish (US)
Pages (from-to)1994-1999
Number of pages6
JournalCritical care medicine
Volume37
Issue number6
DOIs
StatePublished - May 2009

Keywords

  • Low volume resuscitation
  • Metabolic acidosis
  • Na /H exchanger
  • Organ function
  • Proinflammatory mediator
  • Traumatic hemorrhagic shock

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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