Parenteral administration of glipizide sodium salt, an inhibitor of adenosine triphosphate-sensitive potassium channels, prolongs short-term survival after severe controlled hemorrhage in rats

Oleg V. Evgenov, Pál Pacher, William Williams, Natalia V. Evgenov, Jon G. Mabley, James Cicila, Zsombor B. Sikó, Andrew L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Objective: Recent experimental evidence suggests that activation of adenosine triphosphate (ATP)-sensitive potassium channels contributes to vascular failure and early mortality after hemorrhagic shock. The present investigation evaluated the effects of the water-soluble sodium salt of glipizide, an inhibitor of ATP-sensitive potassium channels, in anesthetized and awake rats subjected to severe controlled hemorrhage. Design: Prospective, randomized, controlled study. Setting: Animal research laboratory. Subjects: Male Wistar rats. Interventions: Anesthetized rats were subjected to bleeding to reduce mean arterial pressure to either 40 or 35 mm Hg, which was maintained constant for 60 mins. In addition, awake rats underwent blood withdrawal of 4. 25 mL/100 g over 20 mins. At the end of the hemorrhage period and 30 mins later, the animals received intravenous (5 and 20 mg/kg) or intramuscular (10 and 40 mg/kg) injections of glipizide sodium salt or vehicle. Measurements and Main Results: In anesthetized rats subjected to pressure-controlled hemorrhage, glipizide sodium salt improved mean arterial pressure in a dose-dependent manner. Compared with the vehicle-treated animals, mean arterial pressure increased from 41.6 ± 4.6 to 63.1 ± 3.1 mm Hg in the 20 mg/kg intravenous group and from 33.2 ± 4.9 to 54.0 ± 4.7 mm Hg in the 40 mg/kg intramuscular group 60 mins after a 40-mm Hg shock. Furthermore, the drug did not affect the hemorrhage-induced changes in blood glucose concentrations. However, the higher doses of glipizide sodium salt attenuated the increments in plasma concentrations of lactate, alanine aminotransferase, creatinine, and amylase. Moreover, the higher doses markedly improved short-term survival after pressure- and volume-controlled bleeding. Overall, the intramuscular injections of the drug exerted salutary effects that were comparable to the intravenous administration. Conclusions: In rats, parenteral administration of the water-soluble glipizide sodium salt attenuates vascular and end-organ dysfunction associated with severe hemorrhagic shock and prolongs short-term survival. The intramuscular administration provides comparable benefits as obtained by the intravenous injection.

Original languageEnglish (US)
Pages (from-to)2429-2436
Number of pages8
JournalCritical Care Medicine
Volume31
Issue number10
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

Fingerprint

Glipizide
Potassium Channels
Salts
Adenosine Triphosphate
Sodium
Hemorrhage
Arterial Pressure
Hemorrhagic Shock
Blood Vessels
Pressure
Water
Intramuscular Injections
Amylases
Alanine Transaminase
Intravenous Injections
Pharmaceutical Preparations
Intravenous Administration
Blood Glucose
Wistar Rats
Shock

Keywords

  • Adenosine triphosphate-sensitive potassium channels
  • Hemorrhage
  • Mean arterial pressure
  • Resuscitation
  • Shock
  • Survival

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Parenteral administration of glipizide sodium salt, an inhibitor of adenosine triphosphate-sensitive potassium channels, prolongs short-term survival after severe controlled hemorrhage in rats. / Evgenov, Oleg V.; Pacher, Pál; Williams, William; Evgenov, Natalia V.; Mabley, Jon G.; Cicila, James; Sikó, Zsombor B.; Salzman, Andrew L.; Szabo, Csaba.

In: Critical Care Medicine, Vol. 31, No. 10, 01.10.2003, p. 2429-2436.

Research output: Contribution to journalArticle

Evgenov, Oleg V. ; Pacher, Pál ; Williams, William ; Evgenov, Natalia V. ; Mabley, Jon G. ; Cicila, James ; Sikó, Zsombor B. ; Salzman, Andrew L. ; Szabo, Csaba. / Parenteral administration of glipizide sodium salt, an inhibitor of adenosine triphosphate-sensitive potassium channels, prolongs short-term survival after severe controlled hemorrhage in rats. In: Critical Care Medicine. 2003 ; Vol. 31, No. 10. pp. 2429-2436.
@article{b443d834cf5b4492a3713f3a6b4dee68,
title = "Parenteral administration of glipizide sodium salt, an inhibitor of adenosine triphosphate-sensitive potassium channels, prolongs short-term survival after severe controlled hemorrhage in rats",
abstract = "Objective: Recent experimental evidence suggests that activation of adenosine triphosphate (ATP)-sensitive potassium channels contributes to vascular failure and early mortality after hemorrhagic shock. The present investigation evaluated the effects of the water-soluble sodium salt of glipizide, an inhibitor of ATP-sensitive potassium channels, in anesthetized and awake rats subjected to severe controlled hemorrhage. Design: Prospective, randomized, controlled study. Setting: Animal research laboratory. Subjects: Male Wistar rats. Interventions: Anesthetized rats were subjected to bleeding to reduce mean arterial pressure to either 40 or 35 mm Hg, which was maintained constant for 60 mins. In addition, awake rats underwent blood withdrawal of 4. 25 mL/100 g over 20 mins. At the end of the hemorrhage period and 30 mins later, the animals received intravenous (5 and 20 mg/kg) or intramuscular (10 and 40 mg/kg) injections of glipizide sodium salt or vehicle. Measurements and Main Results: In anesthetized rats subjected to pressure-controlled hemorrhage, glipizide sodium salt improved mean arterial pressure in a dose-dependent manner. Compared with the vehicle-treated animals, mean arterial pressure increased from 41.6 ± 4.6 to 63.1 ± 3.1 mm Hg in the 20 mg/kg intravenous group and from 33.2 ± 4.9 to 54.0 ± 4.7 mm Hg in the 40 mg/kg intramuscular group 60 mins after a 40-mm Hg shock. Furthermore, the drug did not affect the hemorrhage-induced changes in blood glucose concentrations. However, the higher doses of glipizide sodium salt attenuated the increments in plasma concentrations of lactate, alanine aminotransferase, creatinine, and amylase. Moreover, the higher doses markedly improved short-term survival after pressure- and volume-controlled bleeding. Overall, the intramuscular injections of the drug exerted salutary effects that were comparable to the intravenous administration. Conclusions: In rats, parenteral administration of the water-soluble glipizide sodium salt attenuates vascular and end-organ dysfunction associated with severe hemorrhagic shock and prolongs short-term survival. The intramuscular administration provides comparable benefits as obtained by the intravenous injection.",
keywords = "Adenosine triphosphate-sensitive potassium channels, Hemorrhage, Mean arterial pressure, Resuscitation, Shock, Survival",
author = "Evgenov, {Oleg V.} and P{\'a}l Pacher and William Williams and Evgenov, {Natalia V.} and Mabley, {Jon G.} and James Cicila and Sik{\'o}, {Zsombor B.} and Salzman, {Andrew L.} and Csaba Szabo",
year = "2003",
month = "10",
day = "1",
doi = "10.1097/01.CCM.0000089639.84344.A7",
language = "English (US)",
volume = "31",
pages = "2429--2436",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - Parenteral administration of glipizide sodium salt, an inhibitor of adenosine triphosphate-sensitive potassium channels, prolongs short-term survival after severe controlled hemorrhage in rats

AU - Evgenov, Oleg V.

AU - Pacher, Pál

AU - Williams, William

AU - Evgenov, Natalia V.

AU - Mabley, Jon G.

AU - Cicila, James

AU - Sikó, Zsombor B.

AU - Salzman, Andrew L.

AU - Szabo, Csaba

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Objective: Recent experimental evidence suggests that activation of adenosine triphosphate (ATP)-sensitive potassium channels contributes to vascular failure and early mortality after hemorrhagic shock. The present investigation evaluated the effects of the water-soluble sodium salt of glipizide, an inhibitor of ATP-sensitive potassium channels, in anesthetized and awake rats subjected to severe controlled hemorrhage. Design: Prospective, randomized, controlled study. Setting: Animal research laboratory. Subjects: Male Wistar rats. Interventions: Anesthetized rats were subjected to bleeding to reduce mean arterial pressure to either 40 or 35 mm Hg, which was maintained constant for 60 mins. In addition, awake rats underwent blood withdrawal of 4. 25 mL/100 g over 20 mins. At the end of the hemorrhage period and 30 mins later, the animals received intravenous (5 and 20 mg/kg) or intramuscular (10 and 40 mg/kg) injections of glipizide sodium salt or vehicle. Measurements and Main Results: In anesthetized rats subjected to pressure-controlled hemorrhage, glipizide sodium salt improved mean arterial pressure in a dose-dependent manner. Compared with the vehicle-treated animals, mean arterial pressure increased from 41.6 ± 4.6 to 63.1 ± 3.1 mm Hg in the 20 mg/kg intravenous group and from 33.2 ± 4.9 to 54.0 ± 4.7 mm Hg in the 40 mg/kg intramuscular group 60 mins after a 40-mm Hg shock. Furthermore, the drug did not affect the hemorrhage-induced changes in blood glucose concentrations. However, the higher doses of glipizide sodium salt attenuated the increments in plasma concentrations of lactate, alanine aminotransferase, creatinine, and amylase. Moreover, the higher doses markedly improved short-term survival after pressure- and volume-controlled bleeding. Overall, the intramuscular injections of the drug exerted salutary effects that were comparable to the intravenous administration. Conclusions: In rats, parenteral administration of the water-soluble glipizide sodium salt attenuates vascular and end-organ dysfunction associated with severe hemorrhagic shock and prolongs short-term survival. The intramuscular administration provides comparable benefits as obtained by the intravenous injection.

AB - Objective: Recent experimental evidence suggests that activation of adenosine triphosphate (ATP)-sensitive potassium channels contributes to vascular failure and early mortality after hemorrhagic shock. The present investigation evaluated the effects of the water-soluble sodium salt of glipizide, an inhibitor of ATP-sensitive potassium channels, in anesthetized and awake rats subjected to severe controlled hemorrhage. Design: Prospective, randomized, controlled study. Setting: Animal research laboratory. Subjects: Male Wistar rats. Interventions: Anesthetized rats were subjected to bleeding to reduce mean arterial pressure to either 40 or 35 mm Hg, which was maintained constant for 60 mins. In addition, awake rats underwent blood withdrawal of 4. 25 mL/100 g over 20 mins. At the end of the hemorrhage period and 30 mins later, the animals received intravenous (5 and 20 mg/kg) or intramuscular (10 and 40 mg/kg) injections of glipizide sodium salt or vehicle. Measurements and Main Results: In anesthetized rats subjected to pressure-controlled hemorrhage, glipizide sodium salt improved mean arterial pressure in a dose-dependent manner. Compared with the vehicle-treated animals, mean arterial pressure increased from 41.6 ± 4.6 to 63.1 ± 3.1 mm Hg in the 20 mg/kg intravenous group and from 33.2 ± 4.9 to 54.0 ± 4.7 mm Hg in the 40 mg/kg intramuscular group 60 mins after a 40-mm Hg shock. Furthermore, the drug did not affect the hemorrhage-induced changes in blood glucose concentrations. However, the higher doses of glipizide sodium salt attenuated the increments in plasma concentrations of lactate, alanine aminotransferase, creatinine, and amylase. Moreover, the higher doses markedly improved short-term survival after pressure- and volume-controlled bleeding. Overall, the intramuscular injections of the drug exerted salutary effects that were comparable to the intravenous administration. Conclusions: In rats, parenteral administration of the water-soluble glipizide sodium salt attenuates vascular and end-organ dysfunction associated with severe hemorrhagic shock and prolongs short-term survival. The intramuscular administration provides comparable benefits as obtained by the intravenous injection.

KW - Adenosine triphosphate-sensitive potassium channels

KW - Hemorrhage

KW - Mean arterial pressure

KW - Resuscitation

KW - Shock

KW - Survival

UR - http://www.scopus.com/inward/record.url?scp=0142120387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0142120387&partnerID=8YFLogxK

U2 - 10.1097/01.CCM.0000089639.84344.A7

DO - 10.1097/01.CCM.0000089639.84344.A7

M3 - Article

VL - 31

SP - 2429

EP - 2436

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 10

ER -