Tezosentan decreases pulmonary artery pressure and improves survival rate in an animal model of meconium aspiration

被引:14
作者
Geiger, R
Pajk, W
Neu, N
Maier, S
Kleinsasser, A
Fratz, S
Navarro-Psiha, S
Fischer, V
Treml, B
Loeckinger, A
机构
[1] Innsbruck Med Univ, Clin Div Pediat Cardiol, A-6020 Innsbruck, Austria
[2] Innsbruck Med Univ, Clin Div Pediat Intens Care, A-6020 Innsbruck, Austria
[3] Innsbruck Med Univ, Clin Div Neonatol, A-6020 Innsbruck, Austria
[4] Innsbruck Med Univ, Clin Div Anesthesiol & Clin Care Med, A-6020 Innsbruck, Austria
[5] German Heart Ctr Munich, Dept Pediat Cardiol & Congenital Heart Dis, D-80636 Munich, Germany
关键词
D O I
10.1203/01.pdr.0000191813.60977.bf
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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 (.) m(2) to 5.2 +/- 0.7 mm Hg (.) L-1 (.) min (.) m(2). 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.
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收藏
页码:147 / 150
页数:4
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