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.
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
Raphael
R
Briot
Sam
S
Bayat
Daniel
D
Anglade
Jean-Louis
JL
Martiel
Francis
F
Grimbert
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