Inhibition of alveolar Na transport and LPS causes hypoxemia and pulmonary arterial vasoconstriction in ventilated rats.
Oxygen diffusion across the alveolar wall is compromised by low alveolar oxygen but also by pulmonary edema, and leads to hypoxemia and hypoxic pulmonary vasoconstriction (HPV). To test, whether inhibition of alveolar fluid reabsorption results in an increased pulmonary arterial pressure and whether this effect enhances HPV, we established a model, where anesthetized rats were ventilated with normoxic (21% O2) and hypoxic (13.5% O2) gas received aerosolized amiloride and lipopolisaccharide (LPS) to inhibit alveolar fluid reabsorption. Right ventricular systolic pressure (RVsP) was measured as an indicator of pulmonary arterial pressure. Oxygen pressure (PaO2) and saturation (SaO2) in femoral arterial blood served as indicator of oxygen diffusion across the alveolar wall. Aerosolized amiloride and bacterial LPS decreased PaO2and SaO2and increased RVsP even when animals were ventilated with normoxic gas. Ventilation with hypoxic gas decreased PaO2by 35 mmHg and increased RVsP by 10 mmHg. However, combining hypoxia with amiloride and LPS did not aggravate the decrease in PaO2and SaO2and had no effect on the increase in RVsP relative to hypoxia alone. There was a direct relation between SaO2and PaO2and the RVsP under all experimental conditions. Two hours but not 1 h exposure to aerosolized amiloride and LPS in normoxia as well as hypoxia increased the lung wet-to-dry-weight ratio indicating edema formation. Together these findings indicate that inhibition of alveolar reabsorption causes pulmonary edema, impairs oxygen diffusion across the alveolar wall, and leads to an increased pulmonary arterial pressure.
Medical Clinic VII, Sports Medicine, University of Heidelberg, Heidelberg, Germany.
Bodo
B
Davieds
Medical Clinic VII, Sports Medicine, University of Heidelberg, Heidelberg, Germany.
Julian
J
Gross
Department of Anesthesiology, Perioperative and General Critical Care Medicine Salzburg General Hospital Paracelsus Medical University, Salzburg, Austria.
Marc M
MM
Berger
Medical Clinic VII, Sports Medicine, University of Heidelberg, Heidelberg, Germany Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany Department of Pharmacology, Acibadem University, Istanbul, Turkey.
Emel
E
Baloğlu
Medical Clinic VII, Sports Medicine, University of Heidelberg, Heidelberg, Germany.
Peter
P
Bärtsch
Medical Clinic VII, Sports Medicine, University of Heidelberg, Heidelberg, Germany Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany heimo.mairbaeurl@med.uni-heidelberg.de.
Heimo
H
Mairbäurl
Alveolar reabsorption; amiloride; hypoxia; inflammation; pulmonary edema; pulmonary vascular resistance
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