POSTTREATMENT WITH EICOSATETRAYNOIC ACID DECREASES LUNG EDEMA IN GUINEA-PIGS EXPOSED TO PHOSGENE - THE ROLE OF LEUKOTRIENES

Acetylenic acids such as 5,8,11,14-eicosatetraynoic acid (ETYA), have been shown to be effective in preventing pulmonary edema formation (PE F). In phosgene-exposed guinea pigs, we examined the effects of ETYA o n PEF, measured as real time lung weight gain (lwg). Pulmonary artery pressure (Ppa), airway pressure (Paw), perfusate leukotrienes (LT) C-4 /D-4/E-4/B-4, and lung tissue lipid peroxidation (TBARS) were measured using the isolated, buffer-perfused lung model. Guinea pigs were chal lenged to 175 mg/m(3) (44 ppm) phosgene for 10 minutes giving a concen tration x time product of 1750 mg.min/m(3) (437 ppm.min). Five minutes after removal from the exposure chamber, guinea pigs were treated, ip , with 200 mu L of 100 mu M ETYA. 200 mu l of 50 mu M ETYA was added t o the perfusate every 40 minutes, beginning at 60 minutes after start of exposure (t = 0). There were four groups in this study: air-treated , phosgene-exposed, ETYA-posttreated + phosgene, and ETYA-posttreated + air ETYA-posttreated + phosgene guinea pigs had significantly lower Ppa (P = .006), Paw (P = .009), and lung (P = .016) compared with phos gene-exposed animals. Phosgene exposure reduced LTB4 compared with air -treated controls (P = .09). ETYA-posttreatment + phosgene had signifi cantly increased perfusate LTB4 (P = .0006) compared with phosgene exp osure only group. Total perfusate, LTC4 + LTD4 + LTE4, was not differe nt between phosgene-exposed, air-treated or ETYA-posttreatment + phosg ene over time. Posttreatment with ETYA significant lowered TBARS forma tion, 206 +/- 13 versus 285 +/- 23 nmol/mg protein (P = .016), compare d with phosgene-exposed lungs. Paradoxically, ETYA posttreatment decre ased PEF and lipid peroxidation, but increased sulfidopeptide LT relea se from the lung during perfusion. We conclude that LTC4/D-4/E-4, and B-4, may play different roles than previously thought for PEF in the i solated perfused lung model.