Inhibition of k+-atp channels improves systemic and regional
hemodynamics and cellular energetic status in hemorrhagic shock.
Salzman, Andrew L., Amos Vromen, Alvin Denenberg, and Csaba Szab.
Children's Hospital Medical Center, Division of Critical Care1 and
Department of Pediatric Surgery, 3333 Burnet Avenue, Cincinnati, Ohio
45229, Tel.: (513) 559-4259, Fax: (513) 559-4267
APStracts 3:0408H, 1996.
We have tested whether activation of KATP 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
RingerOs Lactate (RL) (100% volume of shed blood) (n=10) or RL in
combination with the KATP channel antagonist glibenclamide (10 mg/kg
i.v. 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], and ileal mucosal pCO2. Treatment with RL alone
caused only a partial and transient hemodynamic and metabolic
benefit. Glibenclamide treatment of sham-shocked controls (n=6)
transiently increased mesenteric and systemic vascular resistance.
Inhibition of KATP 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.
Received 18 June 1996; accepted in final form 28 August 1996.
APS Manuscript Number H543-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996