Effects of partial liquid ventilation on lung injury in a model of acute respiratory failure: a histologic and morphometric analysis.
OBJECTIVE
To compare the histopathologic changes observed in a sheep model of oleic acid-induced acute respiratory failure during partial liquid ventilation with perflubron with gas ventilation.


METHODS
Randomized, controlled study.


METHODS
Animal laboratory and pathology laboratories of a university hospital.


METHODS
Fourteen healthy adult sheep, weighing 64.9 +/- 6.4 kg.


METHODS
Lung injury was induced with oleic acid (0.15 mL/kg). A tracheostomy tube was inserted, along with systemic and pulmonary artery monitoring catheters. Animals were randomized to undergo either partial liquid ventilation (n = 7) or gas ventilation (n = 7). Animals underwent euthanasia at the end of the 90-min study period, after which the endotracheal tube was clamped with the lungs in expiratory hold at a positive end-expiratory pressure of 5 cm H2O. En bloc excision of the heart and lungs was performed by thoracotomy. Perfusion of the isolated lung vasculature with 2.5% paraformaldehyde and 0.25% glutaraldehyde in a 0.1-M phosphate buffer was performed. Histologic analysis followed.


RESULTS
Gas exchange increased markedly in the animals that underwent partial liquid ventilation compared with the gas-ventilated animals (PaO2 at 90 mins: gas ventilation-treatment group, 40 +/- 8 torr [5.3 +/- 1.1 kPa]; partial liquid ventilation-treatment group, 108 +/- 60 torr [14.4 +/- 8.0 kPa]; p = .004). Lung histologic analysis demonstrated a better overall diffuse alveolar damage score (partial liquid ventilation-treatment group, 12.4 +/- 1.4; gas ventilation-treatment group, 15.0 +/- 1.7; p = .01). In the partial liquid ventilation-treatment group, we observed an increase in mean alveolar diameter (partial liquid ventilation-treatment group, 82.4 +/- 2.9 microm; gas ventilation-treatment group, 67.7 x 3.9 microm; p = .0022) and a decrease in the number of alveoli per high-power field (partial liquid ventilation-treatment group, 25.7 +/- 0.9, gas ventilation-treatment group, 31.4 +/- 2.5; p = .0022), in septal wall thickness (partial liquid ventilation-treatment group, 6.0 +/- 0.6 microm; gas ventilation-treatment group, 8.3 +/- 1.0 microm; p = .0033), and in mean capillary diameter (partial liquid ventilation-treatment group, 13.0 +/- 0.8 microm; gas ventilation-treatment group, 19.9 +/- 1.4 microm; p = .0022).


CONCLUSIONS
Partial liquid ventilation is associated with notable improvement in gas exchange and with a reduction in the histologic and morphologic changes observed in an oleic acid model of acute lung injury.
Quintel
M
M
Department of Anesthesiology, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany.
Heine
M
M
Hirschl
R B
RB
Tillmanns
R
R
Wessendorf
V
V
D000818:Animals; D004195:Disease Models, Animal; D005466:Fluorocarbons / Q000008:administration & dosage*; D006439:Hemodynamics / Q000187:drug effects; D006842:Hydrocarbons, Brominated; D008168:Lung / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D008854:Microscopy, Electron; D019301:Oleic Acid; D011659:Pulmonary Gas Exchange; D012123:Pulmonary Ventilation; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D012756:Sheep
D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D019301:Oleic Acid; C003072:perflubron