Leukotriene D4 increases extravascular lung water in the dog

The peptide leukotrienes have been detected in animals that have received endotoxin injections and also have been associated with patients suffering from the adult respiratory distress syndrome (ARDS). The ability of leukotriene D4 (LTD4) to cause pulmonary capillary permeability changes was investigated in ten anesthetized mongrel dogs. Four dogs were used as controls and six dogs received intravenous LTD4 (0.25 microgram/kg). There was a variable response in that two treated animals showed no apparent effect of LTD4. Analysis of the results from the remaining four treated animals demonstrated a significant increase in extravascular lung water (EVLW) that peaked 3 hr after LTD4 from 5.4 +/- 0.6 to 10.3 +/- 0.5 ml/kg (P less than .01). In these four dogs, EVLW increased before slight, but statistically significant, rises in pulmonary artery wedge pressure (4 +/- 1 to 9 +/- 1 mm Hg, P less than .01) and mean pulmonary artery pressure (13 +/- 1 to 17 +/- 1 mm Hg, P less than .01) occurred. During the same period, cardiac output decreased 56 +/- 7% (P less than .01), but no change in airway resistance was observed. This study is the first in vivo demonstration that LTD4 directly alters pulmonary fluid balance in the dog. We conclude LTD4 can cause increases in EVLW and may be an important mediator of the permeability changes observed in various clinical events that lead to the adult respiratory distress syndrome.