The ATP-sensitive potassium-channel inhibitor glibenclamide improves outcome in an ovine model of hemorrhagic shock

Dirk M. Maybauer, John R. Salsbury, Martin Westphal, Marc O. Maybauer, Andrew L. Salzman, Csaba Szabó, Beena B. Westphal-Varghese, Lillian D. Traber, Daniel L. Traber

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

This study was designed as a prospective laboratory experiment to evaluate the effects of the ATP-sensitive potassium-channel inhibitor glibenclamide on hemodynamics and end-organ function in an ovine model of hemorrhagic shock. Twenty-four adult sheep were anesthetized and surgically prepared to measure hemodynamics of the systemic and pulmonary circulation. The anterior surface of the abdominal aorta was exposed at a location 6 cm superior to the iliac bifurcation. After a 60-min period of stabilization, this location was punctured with a 14-G needle. To induce a hemorrhagic hypotension (mean arterial pressure [MAP] less than 50 mmHg) via bleeding, the needle was left in place for 15 s to insure good blood flow. Thereafter, it was removed, and the abdomen closed. The animals were then randomized to receive either glibenclamide (4 mg/kg over 15 min) or an equal volume of the vehicle, started 1 h postinjury. Hemodynamic variables were measured every 30 min. Compared with the control group, MAP and systemic vascular resistance index (SVRI) were significantly higher in the intervention group throughout the entire 6-h study period. Heal pH and urine output were higher in treated than in control animals (4 h, ileal pH 7.29 ± 0.31 vs. 7.17 ± 0.6; 6 h, urine output 36 ± 9 vs. 7.5 ± 2 mL; P value less than 0.05 each). Because glibenclamide improved both hemodynamics and organ function, it may be a beneficial component in the acute treatment of hemorrhagic shock.

Original languageEnglish (US)
Pages (from-to)387-391
Number of pages5
JournalShock
Volume22
Issue number4
DOIs
StatePublished - Oct 2004
Externally publishedYes

Keywords

  • Glibenclamide
  • Hemodynamic
  • Hemorrhage
  • Resuscitation
  • Sheep
  • Shock
  • Survival
  • Trauma

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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