Tezosentan decreases pulmonary artery pressure and improves survival rate in an animal model of meconium aspiration.
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.
Geiger
Ralf
R
Clinical Division of Pediatric Cardiology, Innsbruck Medical University, Austria. ralf.geiger@uibk.ac.at
Pajk
Werner
W
Neu
Nikolaus
N
Maier
Stephan
S
Kleinsasser
Axel
A
Fratz
Sohrab
S
Navarro-Psiha
Salvador
S
Fischer
Viktoria
V
Treml
Benedikt
B
Loeckinger
Alexander
A
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
D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D013777:Tetrazoles; C120582:tezosentan