Effect of eicosanoid inhibition on the development of pulmonary edema after acute lung injury.
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 that could exacerbate edema accumulation. Therefore we tested the following hypothesis: the total accumulation of pulmonary edema in dogs during a 24- to 28-h period of observation after 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 ONO-3708 (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 h, LWC was significantly less (P < 0.05) in the ONO-3708 group than in the meclofenamate group (a similar trend was seen compared with the placebo group, P = 0.12). After 24-28 h, pulmonary arterial 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- to 28-h 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.
Schuster
D P
DP
Pulmonary and Critical Care Division, Washington University Medical School, St. Louis, Missouri 63110, USA.
Stephenson
A H
AH
Holmberg
S
S
Sandiford
P
P
D000818:Animals; D004285:Dogs; D015777:Eicosanoids / Q000494:pharmacology*; D055370:Lung Injury; D011652:Pulmonary Circulation; D011654:Pulmonary Edema / Q000517:prevention & control*; D011659:Pulmonary Gas Exchange; D013997:Time Factors; D014867:Water / Q000378:metabolism
D015777:Eicosanoids; D014867:Water