The endothelin receptor antagonist, bosentan, in combination with the cyclooxygenase inhibitor, diclofenac, counteracts pulmonary hypertension in porcine endotoxin shock

Critical Care Medicine
M WanecekE Weitzberg

Abstract

To prevent endotoxin-induced pulmonary hypertension in the pig with a combination of a nonpeptide mixed endothelin receptor antagonist, bosentan, and a cyclooxygenase inhibitor, diclofenac. Prospective, controlled trial. Animal laboratory at a large university medical center. Twelve domestic pigs, weighing 17.5 to 27 kg. Endotoxin shock was induced by intravenous infusion of Escherichia coli lipopolysaccharide endotoxin (15 micrograms/kg/hr). Six pigs receiving only endotoxin served as controls. Six pigs were pretreated with intravenous bolus injections of bosentan (5 mg/kg) and diclofenac (3 mg/kg) followed by a continuous bosentan infusion (2.5 mg/kg/hr). Systemic hemodynamics and regional circulation were measured using ultrasonic flow probes. Arterial and mixed venous blood samples were collected regularty for determination of Big endothelin-1-like immunoreactivity, endothelin-1-like immunoreactivity, norepinephrine, and blood gases. The bosentan/diclofenac pretreatment per se significantly decreased mean pulmonary arterial pressure (p < .001), pulmonary vascular resistance index (p < .001), and mean arterial blood pressure (p < .001), but cardiac index did not change. Splenic blood flow increased (p < .01) while renal bloo...Continue Reading

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Citations

Nov 30, 2000·Current Treatment Options in Cardiovascular Medicine·E D Missov, De Marco T
Oct 26, 2000·European Journal of Pharmacology·M WanecekA Oldner
Aug 12, 2003·European Journal of Pharmacology·Mariangela AlbertiniSabah N A Hussain
Apr 20, 2004·Critical Care Medicine·Vladimir N KuklinLars J Bjertnaes
Apr 21, 2006·Critical Care Medicine·Jianpu WangSten M Walther
Nov 30, 2004·Critical Care : the Official Journal of the Critical Care Forum·Dilek MemişZafer Pamukçu
Sep 3, 2005·Critical Care : the Official Journal of the Critical Care Forum·Christoph LangenbergStanislao Morgera
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Apr 5, 2008·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Miklós LipcseyMats B Eriksson
May 13, 2006·Nephron. Physiology·Christoph LangenbergStanislao Morgera
Jan 29, 2009·Shock·Erik Waage NielsenTom E Mollnes
Sep 6, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sarah McKennaClyde J Wright
Jan 21, 2000·Journal of Applied Physiology·S DoiP A Murray
Jan 7, 2000·Anesthesia and Analgesia·P T MurrayJ G Umans

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