Terbutaline lessens protein fluxes across the alveolo-capillary barrier during high-volume ventilation.
OBJECTIVE
To evaluate whether a beta2-adrenergic agonist may reduce acute alveolo-capillary barrier alterations during high-volume ventilation.


METHODS
Experimental study.


METHODS
Animal research laboratory.


METHODS
A total of 48 male Wistar rats.


METHODS
A zone of alveolar flooding was produced by liquid instillation in a distal airway. Proteins in the instilled solution were traced with 99mTc-albumin. 111In, which binds to transferrin, was injected into the systemic circulation. Terbutaline was administered in the instilled solution or intra-peritoneally. Conventional ventilation was applied for 30 min followed by different ventilation strategies for 90 min: conventional ventilation, high-volume ventilation with or without 6 cmH2O PEEP.


RESULTS
Protein fluxes across the alveolar and microvascular barriers were evaluated by scintigraphy. High-volume ventilation resulted in immediate leakage of 99mTc-albumin from alveolar spaces and increased pulmonary uptake of systemic 111In-transferrin. Terbutaline in the instilled solution and PEEP lessened alveolar 99mTc-albumin leakage and pulmonary 111In-transferrin uptake due to high-volume ventilation, whereas terbutaline given intra-peritoneally only lessened 111In-transferrin uptake. Terbutaline in the instilled solution also lessened the increase in lung wet-to-dry weight ratio due to high-volume ventilation.


CONCLUSIONS
Terbutaline reduces protein fluxes across the alveolar epithelial and pulmonary microvascular barriers during high-volume ventilation in vivo. The route of administration may be important.
de Prost
Nicolas
N
INSERM U773, Equipe 11, Centre de Recherche Bichat Beaujon CRB3, BP 416, 75018, Paris, France.
Dreyfuss
Didier
D
Ricard
Jean-Damien
JD
Saumon
Georges
G
D000318:Adrenergic beta-Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D015824:Blood-Air Barrier / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D015633:Extravascular Lung Water / Q000378:metabolism; D007385:Intermittent Positive-Pressure Ventilation / Q000009:adverse effects / Q000379:methods; D008297:Male; D011654:Pulmonary Edema / Q000517:prevention & control*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020545:Respiratory Mucosa / Q000378:metabolism; D013668:Technetium Tc 99m Aggregated Albumin / Q000378:metabolism; D013726:Terbutaline / Q000493:pharmacokinetics / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; D013726:Terbutaline