Combined exogenous surfactant and inhaled nitric oxide therapy for lung ischemia-reperfusion injury in minipigs.
BACKGROUND
The combined application of exogenous surfactant and inhaled nitric oxide was evaluated for prevention of ischemia-reperfusion injury of the lung.


METHODS
Left lungs were selectively perfused in 18 minipigs in situ with cold preservation solution. After 90 min of warm ischemia, the lungs were reperfused and the right pulmonary artery and bronchus were ligated (control group, n=6). Exogenous surfactant was instilled via bronchoscopy during ischemia (surfactant group, n=6). In a third group, surfactant was applied, followed by administration of inhaled nitric oxide (surfactant+NO group, n=6). Hemodynamic and respiratory parameters were recorded for 7 hr, and bronchoalveolar lavage fluid (BALF) was obtained before and after reperfusion for measurement of surface tension, small aggregate/large aggregate ratio, protein and phospholipid contents, and a differential cell count.


RESULTS
Control group animals survived for 3.7+/-1.4 hr. In both surfactant-treated groups, five out of six animals survived the observation period (P<0.001). Dynamic compliance of the lung was decreased in control animals (P<0.001). In the surfactant+NO group, arterial PO2 was higher than in both other groups (P<0.001). BALF cell count and histology showed reduced neutrophil infiltration in surfactant+NO-treated lungs. Surface tension assessed in BALF with a pulsating bubble surfactometer was severely impaired in control animals (gammamin, 14.82+/-9.95 mN/m), but maintained in surfactant-treated (gammamin, 1.11+/-0.56 mN/m) and surfactant+NO-treated animals (gammamin, 3.90+/-2.35 mN/m, P=0.02).


CONCLUSIONS
Administration of exogenous surfactant in lung reperfusion injury results in improved lung compliance. The addition of inhaled NO improves arterial oxygenation and reduces neutrophil extravasation compared with surfactant treatment alone.
Warnecke
G
G
Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Germany.
Strüber
M
M
Fraud
S
S
Hohlfeld
J M
JM
Haverich
A
A
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004359:Drug Therapy, Combination; D006439:Hemodynamics; D008168:Lung / Q000098:blood supply* / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D008170:Lung Compliance; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013501:Surface-Active Agents / Q000627:therapeutic use*; D015996:Survival Rate; D013556:Swine, Miniature; D014867:Water / Q000032:analysis
D013501:Surface-Active Agents; D014867:Water; D009569:Nitric Oxide; D009195:Peroxidase