Hemodynamic effects of glibenclamide during endotoxemia: contrasting findings in vitro versus in vivo.
The final common pathway involved in the cardiovascular alterations of septic shock is incompletely defined. The opening of KATP channels is associated with vasorelaxation and alterations in cardiac contractility. This event may be triggered during septic shock by increased nitric oxide (NO) production, by a decreased intracellular content of ATP, or by a change in the transmembrane electrical potential. In the present study, we assessed the effects of glibenclamide, an agent that blocks the opening of KATP channels in vitro, on the contractile response of rat aortic rings to norepinephrine, and in vivo in anesthetized dogs, with or without exposure to Escherichia coli endotoxin. In vitro, glibenclamide decreased the contractile response to norepinephrine in the presence of endotoxin, provided that the endothelium was intact. In vivo, administration of 0.15 mg/kg increased systemic vascular resistance (SVR) in the absence of endotoxin only, and increased myocardial performance. A higher dose of 1 mg/kg increased SVR and decreased myocardial performance, both during endotoxic shock and in control conditions. Renal and mesenteric blood flows decreased, but the respective fractional flows were unchanged. Oxygen delivery decreased in both experimental conditions, but oxygen consumption decreased only in control conditions. The in vitro observations suggest that the opening of KATP channels is involved in the regulation of vascular tone during endotoxemia, via an endothelium-dependent mechanism. As different effects of glibenclamide were observed in vivo, the importance of the opening of KATP channels in endotoxic shock may be limited.
Preiser
Jean-Charles
JC
Department of Intensive Care, Erasme Hospital, Brussels, Belgium.
Zhang
Haibo
H
Debelle
Frédéric
F
Fesler
Pierre
P
Kafi
Sofia Abdel
SA
Naeije
Robert
R
Vincent
Jean-Louis
JL
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D004285:Dogs; D019446:Endotoxemia / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity; D005905:Glyburide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000503:physiopathology*
D004731:Endotoxins; D005905:Glyburide