title: Tezosentan decreases pulmonary artery pressure and improves survival rate in an animal model of meconium aspiration.
abstract: Acute pulmonary arterial hypertension in acute lung injury aggravates the clinical course and complicates treatment. Increased release and turnover of endogenous endothelin-1 is known to be a major determinant in the pathophysiology of pulmonary arterial hypertension of various etiologies. We tested whether intravenous tezosentan, a dual endothelin receptor antagonist, reduced pulmonary artery pressure in a pig model of acute lung injury induced by meconium aspiration. Acute pulmonary arterial hypertension was induced in 12 anesthetized and instrumented pigs by instillation of human pooled meconium in a 20% solution. Hemodynamic and gas exchange parameters were recorded every 30 min. Six animals received tezosentan 5 mg/kg after 0 and 90 min; six animals served as controls. Tezosentan led to a decrease of mean pulmonary artery pressure (PAP) from 33.4 +/- 4.0 mm Hg to 24.7 +/- 2.1 mm Hg and pulmonary vascular resistance (PVR) from 7.8 +/- 1.4 mm Hg.L(-1).min.m2 to 5.2 +/- 0.7 mm Hg.L(-1).min.m2. All animals treated with tezosentan survived, whereas in the control group four out of six animals died. Tezosentan improved survival and decreased pulmonary artery pressure in a porcine model of acute pulmonary arterial hypertension after meconium aspiration. Tezosentan has the potential for effective pharmacological treatment of pulmonary arterial hypertension following acute lung injury.
authors.affiliation: Clinical Division of Pediatric Cardiology, Innsbruck Medical University, Austria. ralf.geiger@uibk.ac.at
authors.forename: Ralf
authors.initials: R
authors.lastname: Geiger
authors.forename: Werner
authors.initials: W
authors.lastname: Pajk
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Neu
authors.forename: Stephan
authors.initials: S
authors.lastname: Maier
authors.forename: Axel
authors.initials: A
authors.lastname: Kleinsasser
authors.forename: Sohrab
authors.initials: S
authors.lastname: Fratz
authors.forename: Salvador
authors.initials: S
authors.lastname: Navarro-Psiha
authors.forename: Viktoria
authors.initials: V
authors.lastname: Fischer
authors.forename: Benedikt
authors.initials: B
authors.lastname: Treml
authors.forename: Alexander
authors.initials: A
authors.lastname: Loeckinger
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D007231:Infant, Newborn; D008471:Meconium Aspiration Syndrome / Q000188:drug therapy*; D011651:Pulmonary Artery / Q000503:physiopathology; D011659:Pulmonary Gas Exchange; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis; D034421:Sus scrofa; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D013777:Tetrazoles; C120582:tezosentan