KATP-channel inhibition improves hemodynamics and cellular energetics in hemorrhagic shock

Andrew L. Salzman, Amos Vromen, Alvin Denenberg, Csaba Szabo

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

We 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 Ringer lactate (RL; 100% volume of shed blood; n = 10) or RL in combination with the KATP-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 PCO2. 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 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume41
Issue number2
StatePublished - Feb 1997
Externally publishedYes

Fingerprint

KATP Channels
Hemorrhagic Shock
Glyburide
Hemodynamics
Swine
Renal Circulation
Blood Volume
Vasodilation
Resuscitation
Vascular Resistance
Perfusion
Adenosine Triphosphate
Placebos
Blood Pressure
Kidney
Injections
Therapeutics

Keywords

  • Adenosine 5′-triphosphate-sensitive potassium channel
  • Glibenclamide
  • Resuscitation

ASJC Scopus subject areas

  • Physiology

Cite this

KATP-channel inhibition improves hemodynamics and cellular energetics in hemorrhagic shock. / Salzman, Andrew L.; Vromen, Amos; Denenberg, Alvin; Szabo, Csaba.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 41, No. 2, 02.1997.

Research output: Contribution to journalArticle

@article{93038e607dba4539ba2222be3799bb76,
title = "KATP-channel inhibition improves hemodynamics and cellular energetics in hemorrhagic shock",
abstract = "We 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 Ringer lactate (RL; 100{\%} volume of shed blood; n = 10) or RL in combination with the KATP-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 PCO2. 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 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.",
keywords = "Adenosine 5′-triphosphate-sensitive potassium channel, Glibenclamide, Resuscitation",
author = "Salzman, {Andrew L.} and Amos Vromen and Alvin Denenberg and Csaba Szabo",
year = "1997",
month = "2",
language = "English (US)",
volume = "41",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - KATP-channel inhibition improves hemodynamics and cellular energetics in hemorrhagic shock

AU - Salzman, Andrew L.

AU - Vromen, Amos

AU - Denenberg, Alvin

AU - Szabo, Csaba

PY - 1997/2

Y1 - 1997/2

N2 - We 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 Ringer lactate (RL; 100% volume of shed blood; n = 10) or RL in combination with the KATP-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 PCO2. 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 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.

AB - We 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 Ringer lactate (RL; 100% volume of shed blood; n = 10) or RL in combination with the KATP-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 PCO2. 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 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.

KW - Adenosine 5′-triphosphate-sensitive potassium channel

KW - Glibenclamide

KW - Resuscitation

UR - http://www.scopus.com/inward/record.url?scp=33750890884&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750890884&partnerID=8YFLogxK

M3 - Article

VL - 41

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 2

ER -