2004 OPEN FORUM Abstracts
EXOGENOUS KL4 SURFACTANT REDUCES ALVEOLAR OPENING PRESSURE IN SALINE LAVAGE-INJURED LUNGS
Joseph
D DiRocco MD, Lucio A Pavone MD, Charles J Lutz MD, Kathy P
Snyder RN, Gary F Nieman BA. Department of Surgery – SUNY -
Upstate Medical University
Introduction:
Surfactant dysfunction in acute lung injury can cause
heterogeneous patterns of microatelectasis and render alveoli
unstable. High-pressure recruitment maneuvers have been advocated to
open these collapsed alveoli. High peak pressures may also be
injurious. We hypothesize that the administration of an exogenous,
peptide-containing synthetic surfactant (KL4) will reduce
the pressure required to recruit alveoli. We assessed the opening of
alveoli by direct in vivo microscopic observation.
Methods:
Sprague-Dawley rats were mechanically ventilated with 100% O2.
Right thorectomy was performed in all animals for exposure of the
right lung. All rats underwent staged recruitment maneuvers (RM)
while subpleural alveoli were recorded with videomicroscopy (Table,
Baseline). Each RM consisted of 10 cm H2O increments in
airway pressure from 10 to 40 cm H2O. After baseline RM,
all animals were subjected to repeated saline lavage injury until
PaO2 < 150 mm Hg. RM with videomicroscopy were
repeated after injury (Table, Injury). Animals then received either
KL4 (100mg/kg of 30mg/cc, n=5) or buffered saline (3.3
cc/kg, n=3) followed by another RM under videomicroscopy (Table,
Sham Group or KL4 Group). Computer image analysis of the
recorded video at each pressure identified the number of alveoli per
mm2 field and the percent of field with aerated alveoli.
All values reported as mean ± SEM. * = p < 0.05 for ANOVA
and Tukey HSD vs. Baseline, † = p < 0.05 vs. Sham.
Results:
| 10 cm H2O | 20 cm H2O | 30 cm H2O | 40 cm H2O | |
| # Alveoli / mm2 | ||||
| Baseline | 137 ± 6 | 137 ± 6 | 137 ± 6 | 137 ± 6 |
| Injury | 4 ± 1* | 10 ± 1* | 21 ± 2* | 36 ± 3* |
| Sham Group | 5 ± 2* | 12 ± 3* | 24 ± 5* | 39 ± 7* |
| KL4 Group | 25 ± 5* | 36 ± 5*† | 60 ± 5*† | 84 ± 5*† |
| % Aerated | ||||
| Baseline | 44 ± 3 | 46 ± 3 | 43 ± 5 | 46 ± 4 |
| Injury | 4 ± 1* | 10 ± 1* | 17 ± 1* | 21 ± 2* |
| Sham Group | 5 ± 2* | 12 ± 2* | 16 ± 2* | 21 ± 3* |
| KL4 Group | 18 ± 3* | 25 ± 3* | 32 ± 3† | 38 ± 3† |
Conclusion:
In the normal lung, increases in pressure above 10 cm H2O
do not result in further alveolar recruitment. In the injured lung,
the majority of subpleural alveoli were collapsed at 10 cm H2O
and only partially recruited by 40 cm H2O. KL4
surfactant therapy significantly increased the degree of alveolar
recruitment after injury at lower pressures. This reduction of
necessary alveolar recruiting pressure will ameliorate the negative
consequences of recruitment maneuvers.