THE ATP-SENSITIVE POTASSIUM-CHANNEL INHIBITOR GLIBENCLAMIDE IMPROVES OUTCOME IN AN OVINE MODEL OF HEMORRHAGIC SHOCK

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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. Ileal 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.