Increased cardiac index due to terbutaline treatment aggravates capillary-alveolar macromolecular leakage in oleic acid lung injury in dogs.
BACKGROUND
We assessed the in vivo effects of terbutaline, a beta2-agonist assumed to reduce microvascular permeability in acute lung injury.


METHODS
We used a recently developed broncho-alveolar lavage (BAL) technique to repeatedly measure (every 15 min. for 4 hours) the time-course of capillary-alveolar leakage of a macromolecule (fluorescein-labeled dextran) in 19 oleic acid (OA) lung injured dogs. BAL was performed in a closed lung sampling site, using a bronchoscope fitted with an inflatable cuff. Fluorescein-labeled Dextran (FITC-D70) was continuously infused and its concentration measured in plasma and BAL fluid. A two-compartment model (blood and alveoli) was used to calculate KAB, the transport rate coefficient of FITC-D70 from blood to alveoli. KAB was estimated every 15 minutes over 4 hours. Terbutaline intra-venous perfusion was started 90 min. after the onset of the injury and then continuously infused until the end of the experiment.


RESULTS
In the non-treated injured group, the capillary-alveolar leakage of FITC-D70 reached a peak within 30 minutes after the OA injury. Thereafter the FITC-D70 leakage decreased gradually until the end of the experiment. Terbutaline infusion, started 90 min after injury, interrupted the recovery with an aggravation in FITC-D70 leakage.


CONCLUSIONS
As cardiac index increased with terbutaline infusion, we speculate that terbutaline recruits leaky capillaries and increases FITC-D70 leakage after OA injury. These findings suggest that therapies inducing an increase in cardiac output and a decrease in pulmonary vascular resistances have the potential to heighten the early increase in protein transport from plasma to alveoli within the acutely injured lung.
Briot
Raphael
R
Laboratoire TIMC, Equipe PRETA, Unité Mixte de Recherche 5525 du Centre National de Recherche Scientifique, Université Joseph Fourier, Centre Hospitalier Universitaire, Grenoble 38043 cedex 09, France. rbriot@chu-grenoble.fr
Bayat
Sam
S
Anglade
Daniel
D
Martiel
Jean-Louis
JL
Grimbert
Francis
F
D000818:Animals; D018893:Bronchoalveolar Lavage / Q000379:methods; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D019559:Capillary Leak Syndrome / Q000139:chemically induced*; D002302:Cardiac Output / Q000502:physiology*; D003911:Dextrans / Q000032:analysis / Q000097:blood*; D004285:Dogs; D055370:Lung Injury / Q000097:blood* / Q000139:chemically induced; D008991:Monitoring, Physiologic; D019301:Oleic Acid / Q000009:adverse effects*; D011650:Pulmonary Alveoli / Q000098:blood supply* / Q000503:physiopathology; D013726:Terbutaline / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D001993:Bronchodilator Agents; D003911:Dextrans; D019301:Oleic Acid; D013726:Terbutaline