Intravenous tezosentan improves gas exchange and hemodynamics in acute lung injury secondary to meconium aspiration.
OBJECTIVE
Meconium aspiration induces acute lung injury (ALI) and subsequent pulmonary arterial hypertension (PAH) which may lead to right ventricular failure. Increase of endothelin-1, thromboxane-A, and phosphodiesterases are discussed molecular mechanisms. We investigated the intrapulmonary and hemodynamic effects of the intravenous dual endothelin A and B receptor blocker tezosentan and inhalational iloprost in a model of ALI due to meconium aspiration.


METHODS
Animal study.


METHODS
University-affiliated research laboratory.


METHODS
White farm pigs.


METHODS
Acute lung injury was induced in 24 pigs by instillation of meconium. Animals were randomly assigned to four groups to receive either intravenous tezosentan, inhalational iloprost, or combined tezosentan and iloprost, or to serve as controls.


RESULTS
After meconium aspiration-induced lung injury each treatment increased oxyhemoglobin saturations (TEZO: 88 +/- 6% (p = 0.02), ILO: 85 +/- 13% (p = 0.05), TEZO-ILO: 89 +/- 6% (p = 0.02), control: 70 +/- 18%). TEZO but not ILO significantly decreased pulmonary arterial pressure and pulmonary vascular resistance (both p < 0.01). ILO alone decreased intrapulmonary shunt blood flow (p < 0.01). Compared with control, TEZO-ILO yielded the highest arterial partial pressure of oxygen (70 +/- 6 torr vs.49 +/- 9 torr, p = 0.04), although it decreased arterial blood pressure (change from 71 +/- 13 mmHg to 62 +/- 12 mmHg vs.85 +/- 14 mmHg to 80 +/- 11 mmHg (p = 0.01).


CONCLUSIONS
Intravenous TEZO improves pulmonary gas exchange and hemodynamics in experimental acute lung injury secondary to meconium aspiration. Inhaled ILO improves gas exchange only, thereby reducing intrapulmonary shunt blood flow. Combination of TEZO and ILO marginally improves pulmonary gas exchange at the disadvantage of pulmonary selectivity.
Geiger
Ralf
R
Innsbruck Medical University, Clinical Division of Pediatric Cardiology, Pulmology, Allergology and Cystic Fibrosis, Anichstrasse 35, 6020 Innsbruck, Austria. ralf.geiger@i-med.ac.at
Kleinsasser
Axel
A
Meier
Stephan
S
Neu
Nikolaus
N
Pajk
Werner
W
Fischer
Victoria
V
Treml
Benedict
B
Stein
Joerg I
JI
Loeckinger
Alexander
A
D000704:Analysis of Variance; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D007231:Infant, Newborn; D007275:Injections, Intravenous; D008471:Meconium Aspiration Syndrome; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology*; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology*
D011725:Pyridines; D013777:Tetrazoles; C120582:tezosentan; D016285:Iloprost