K(ATP)-channel inhibition improves hemodynamics and cellular energetics in hemorrhagic shock.
We tested whether activation of K(ATP) channels contributes to vasodilatation and end-organ hypoperfusion in severe hemorrhagic shock (HS). Anesthetized juvenile pigs were hemorrhaged to a portal blood flow of 45% of baseline for 45 min and then resuscitated with Ringer lactate (RL; 100% volume of shed blood; n = 10) or RL in combination with the K(ATP)-channel antagonist glibenclamide (10 mg/kg iv bolus injection; n = 10). Addition of glibenclamide to the resuscitation fluid caused a sustained recovery of systemic blood pressure, cardiac index, portal blood flow, renal blood flow, renal cortical ATP concentration, and ileal mucosal P(CO2). Treatment with RL alone caused only a partial and transient hemodynamic and metabolic benefit. Glibenclamide treatment of sham-shocked control pigs (n = 6) transiently increased mesenteric and systemic vascular resistance. Inhibition of K(ATP)-channel activity in HS, which effectively and safely restores systemic hemodynamics, regional perfusion, and tissue metabolism, is a potentially novel therapeutic approach to the management of severe HS.
Salzman
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AL
Division of Critical Care, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Vromen
A
A
Denenberg
A
A
Szabó
C
C
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D004734:Energy Metabolism; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D026902:Potassium Channel Blockers; D012151:Resuscitation; D000077325:Ringer's Lactate; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D013552:Swine
D007552:Isotonic Solutions; D026902:Potassium Channel Blockers; D000077325:Ringer's Lactate; D000255:Adenosine Triphosphate; D010100:Oxygen; D005905:Glyburide