Short-term effects of glipizide (an adenosine triphosphate-sensitive potassium channel inhibitor) on cardiopulmonary hemodynamics and global oxygen transport in healthy and endotoxemic sheep

Matthias Lange, Csaba Szabo, Hugo Van Aken, William Williams, Daniel L. Traber, Fritz Daudel, Katrin Bröking, Andrew L. Salzman, Hans Georg Bone, Martin Westphal

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

In severe sepsis and septic shock, hemodynamic support is often complicated by a tachyphylaxis against exogenous catecholamines. Because activation of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels plays a pivotal role in the pathogenesis of hyperdynamic vasodilatory shock, we hypothesized that it may be beneficial to administer a specific KATP channel inhibitor to prevent, or at least attenuate, hemodynamic dysfunction in sepsis. The present study was designed as a prospective and controlled laboratory experiment to elucidate the short-term effects of glipizide, a specific KATP channel inhibitor, on cardiopulmonary hemodynamics and global oxygen transport in healthy sheep and sheep with endotoxemia. Ten adult ewes were anesthetized and operatively instrumented with a pulmonary artery, a femoral artery, and a foley catheter. After 24 h of recovery, healthy sheep received glipizide as a bolus infusion (4 mg/kg over 15 min). After 24 h of recovery, a continuous infusion of endotoxin (Salmonella typhosa, 10 ng·kg·min) was started in the same sheep and administered for the next 17 h. After 16 h of endotoxemia, glipizide was given as described above. Administration of glipizide was followed by a transient, but significant, increase in mean arterial pressure in both healthy controls (95 ± 3 mmHg vs. 101 ± 2 mmHg, P < 0.05) and sheep with endotoxemia (86 ± 3 mmHg vs. 93 ± 3 mmHg, P < 0.05). However, the increase in mean arterial pressure was longer lasting in ewes with endotoxemia. Cardiac index, oxygen delivery index, arterial lactate concentrations, and arterial pH were not significantly affected by glipizide. Therefore, administration of glipizide may represent a beneficial therapeutic option to treat arterial hypotension resulting from sepsis and systemic inflammatory response syndrome. Additional studies are required to determine the effects of continuous infusion of glipizide in the presence of systemic inflammation.

Original languageEnglish (US)
Pages (from-to)516-521
Number of pages6
JournalShock
Volume26
Issue number5
DOIs
StatePublished - Nov 2006
Externally publishedYes

Fingerprint

Glipizide
Potassium Channels
Sheep
Adenosine Triphosphate
Hemodynamics
Oxygen
Endotoxemia
KATP Channels
Sepsis
Arterial Pressure
Tachyphylaxis
Systemic Inflammatory Response Syndrome
Salmonella typhi
Femoral Artery
Septic Shock
Endotoxins
Hypotension
Pulmonary Artery
Catecholamines
Shock

Keywords

  • Endotoxemia
  • Glipizide
  • K-channel inhibition
  • Sepsis
  • Sheep
  • Systemic inflammatory response syndrome

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Cite this

Short-term effects of glipizide (an adenosine triphosphate-sensitive potassium channel inhibitor) on cardiopulmonary hemodynamics and global oxygen transport in healthy and endotoxemic sheep. / Lange, Matthias; Szabo, Csaba; Van Aken, Hugo; Williams, William; Traber, Daniel L.; Daudel, Fritz; Bröking, Katrin; Salzman, Andrew L.; Bone, Hans Georg; Westphal, Martin.

In: Shock, Vol. 26, No. 5, 11.2006, p. 516-521.

Research output: Contribution to journalArticle

Lange, Matthias ; Szabo, Csaba ; Van Aken, Hugo ; Williams, William ; Traber, Daniel L. ; Daudel, Fritz ; Bröking, Katrin ; Salzman, Andrew L. ; Bone, Hans Georg ; Westphal, Martin. / Short-term effects of glipizide (an adenosine triphosphate-sensitive potassium channel inhibitor) on cardiopulmonary hemodynamics and global oxygen transport in healthy and endotoxemic sheep. In: Shock. 2006 ; Vol. 26, No. 5. pp. 516-521.
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