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Hypoxia causes permeability oedema in the constant-pressure perfused rat lung

Medical Clinic VII, Sports Medicine, University Hospital Heidelberg, Heidelberg, Germany

CORRESPONDENCE: H. Mairbäurl, Medical Clinic VII, Sports Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Fax: 49 6221565972. E-mail: heimo.mairbaeurl{at}med.uni-heidelberg.de

Keywords: Beta-adrenergic agonists, capillary permeability, cyclic adenosine monophosphate, hypoxia, pulmonary oedema

Received: May 27, 2005
Accepted November 10, 2005

Alveolar hypoxia causes pulmonary oedema associated with increased lung capillary pressure and decreased alveolar fluid reabsorption. However, the role of altered permeability is unclear. The aim of the present study was to test whether hypoxia affects alveolar permeability and induces pulmonary oedema in rat lungs, and whether terbutaline affects oedema formation.

Isolated lungs of normoxic rats were perfused at a constant pressure (12 cmH₂O) and exposed to different levels of oxygenation (1.5–35% O₂). Terbutaline (10^–5 M) was applied as an aerosol or with the perfusate. Online measurements indicate an earlier onset of weight gain with an increasing degree of hypoxia and a shortened lung survival time (35% O₂: 220 min; 1.5% O₂: 120 min). Terbutaline did not prevent oedema formation in hypoxic lungs. The terbutaline-induced formation of cyclic adenosine monophosphate was decreased by 50% in hypoxia (1.5% O₂).

In experiments terminated after 75 min, bronchoalveolar lavage fluid of hypoxic lungs contained protein that originated from perfusate indicating alveolar leakage. Since lactate dehydrogenase in perfusate was not increased at the onset of oedema formation, cell damage does not explain the increased permeability.

In conclusion, these results indicate the formation of a leak for macromolecules of the isolated perfused rat lung, which is accelerated by hypoxia and causes alveolar flooding even at low perfusion pressure at a rate that exceeds absorption even after stimulation with terbutaline.

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