Effect of eicosanoid inhibition on the development of pulmonary
edema after acute lung injury.
Schuster, Daniel P., Alan H. Stephenson, Sandra Holmberg, Patrick
Sandiford.
Pulmonary and Critical Care Division, Washington University Medical
School and the Department of Pharmacological and Physiological
Science, St. Louis University School of Medicine
APStracts 2:0494A, 1995.
In experimental models of acute lung injury, cyclooxygenase inhibition
improves oxygenation, presumably by causing a redistribution of blood
flow away from edematous lung regions. This effect on perfusion
pattern could also reduce alveolar edema formation. On the other
hand, pulmonary pressures usually increase after cyclooxygenase
inhibition, an effect which could exacerbate edema accumulation.
Therefore, we tested the following hypothesis: the total accumulation
of pulmonary edema in dogs during a 24-28 hr period of observation
following acute lung injury caused by oleic acid will be less in a
group of animals treated with meclofenamate (n=6) or with the
thromboxane receptor blocker ONO3708 (n=5) than in a group of animals
treated with oleic acid alone (placebo) (n=6). Lung water
concentrations (LWC), the regional pattern of pulmonary perfusion,
and protein permeability were measured with the nuclear medicine
imaging technique of positron emission tomography. After 24-28 hrs,
LWC in the ONO3708 group was significantly less (p<0.05) than in
the meclofenamate group (a similar trend was seen when compared to
the placebo group with p=0.12). After 24-28 hr, pulmonary artery
pressures were highest in the meclofenamate group. Regardless of
group, the only significant correlation with the change in LWC was
with the integral of pulmonary pressures over the 24-28 hr period.
The data suggest that thromboxane inhibition will reduce edema
accumulation in acute lung injury, but that this effect depends on
reducing as much as possible the simultaneous development of
pulmonary hypertension from other causes.
Received 19 July 1995; accepted in final form 27 October 1995.
APS Manuscript Number A786-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95