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01.02.2008 | Experimental

Intravenous tezosentan improves gas exchange and hemodynamics in acute lung injury secondary to meconium aspiration

verfasst von: Ralf Geiger, Axel Kleinsasser, Stephan Meier, Nikolaus Neu, Werner Pajk, Victoria Fischer, Benedict Treml, Joerg I. Stein, Alexander Loeckinger

Erschienen in: Intensive Care Medicine | Ausgabe 2/2008

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Abstract

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.

Design

Animal study.

Setting

University-affiliated research laboratory.

Subjects

White farm pigs.

Interventions

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.

Measurements and 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.

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Titel: Intravenous tezosentan improves gas exchange and hemodynamics in acute lung injury secondary to meconium aspiration
verfasst von: Ralf Geiger
Axel Kleinsasser
Stephan Meier
Nikolaus Neu
Werner Pajk
Victoria Fischer
Benedict Treml
Joerg I. Stein
Alexander Loeckinger
Publikationsdatum: 01.02.2008
Verlag: Springer-Verlag
Erschienen in: Intensive Care Medicine / Ausgabe 2/2008
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-007-0857-y

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Intravenous tezosentan improves gas exchange and hemodynamics in acute lung injury secondary to meconium aspiration