The ATP-sensitive potassium-channel inhibitor glibenclamide improves outcome in an ovine model of hemorrhagic shock.
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.
Maybauer
Dirk M
DM
Department of Anesthesiology, University of Texas Medical Branch, and Shriners Burns Hospital for Children, Galveston, Texas 77555-0833, USA. dmmaybau@utmb.edu
Salsbury
John R
JR
Westphal
Martin
M
Maybauer
Marc O
MO
Salzman
Andrew L
AL
Szabó
Csaba
C
Westphal-Varghese
Beena B
BB
Traber
Lillian D
LD
Traber
Daniel L
DL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011446:Prospective Studies; D011897:Random Allocation; D012756:Sheep; D012771:Shock, Hemorrhagic / Q000188:drug therapy*; D014554:Urination / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D026902:Potassium Channel Blockers; D005905:Glyburide