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

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-alpha, 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.

• Authors: Dongmei Wu, Hui Dai, Jaqueline Arias, Loren Latta, William M Abraham
• Journal: Critical care medicine (Crit Care Med) Vol. 37 Issue 6 Pg. 1994-9 (Jun 2009) ISSN: 1530-0293 [Electronic] United States
• PMID: 19384202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Mesylates
• Sodium-Hydrogen Exchangers
• BIIB 513

Topics

• Animals
• Male
• Mesylates (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Resuscitation (methods)
• Shock, Hemorrhagic (etiology, therapy)
• Sodium-Hydrogen Exchangers (antagonists & inhibitors)
• Wounds and Injuries (complications)