Acetylenic
acids such as
5,8,11,14-eicosatetraynoic acid (
ETYA), have been shown to be effective in preventing
pulmonary edema formation (PEF). In
phosgene-exposed guinea pigs, we examined the effects of
ETYA on PEF, measured as real time lung
weight gain (lwg). Pulmonary artery pressure (Ppa), airway pressure (Paw), perfusate
leukotrienes (LT) C4/D4/E4/B4, and lung tissue lipid peroxidation (
TBARS) were measured using the isolated,
buffer-perfused lung model. Guinea pigs were challenged to 175 mg/m3 (44 ppm)
phosgene for 10 minutes giving a concentration x time product of 1750 mg.min/m3 (437 ppm.min). Five minutes after removal from the exposure chamber, guinea pigs were treated, i.p., with 200 microL of 100 microM
ETYA. 200 microL of 50 microM
ETYA was added to 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 lwg (P = .016) compared with
phosgene-exposed animals.
Phosgene exposure reduced
LTB4 compared with air-treated controls (P = .09).
ETYA-posttreatment +
phosgene had significantly increased perfusate
LTB4 (P = .0006) compared with
phosgene exposure only group. Total perfusate,
LTC4 +
LTD4 +
LTE4, was not different between
phosgene-exposed, air-treated or
ETYA-posttreatment +
phosgene over time. Posttreatment with
ETYA significantly lowered
TBARS formation, 206 +/- 13 versus 285 +/- 23 nmol/mg
protein (P = .016), compared with
phosgene-exposed lungs. Paradoxically,
ETYA posttreatment decreased PEF and lipid peroxidation, but increased sulfidopeptide LT release from the lung during perfusion. We conclude that
LTC4/D4/E4, and B4, may play different roles than previously thought for PEF in the isolated perfused lung model.