Increased leukotriene C4 in ethchlorvynol-induced acute lung injury in dogs.
We investigated whether ethchlorvynol (ECV)-induced acute lung injury (ALI) is associated with an increase in leukotriene C4 (LTC4) production. In six pentobarbital sodium-anesthetized dogs, ECV (15 mg/kg iv) introduced into the pulmonary circulation resulted in a 164 +/- 31% increase in extravascular lung water 120 min after ECV administration. Concomitantly, the mean (+/- SE) concentration of LTC4 in arterial plasma measured by radioimmunoassay following 80% EtOH precipitation, XAD-7 extraction and high-pressure liquid chromatography purification was 5.0 +/- 1.3 pg/ml, unchanged from control (pre-ECV) values. In contrast, in pulmonary edema fluid 120 min post-ECV, the LTC4 concentration was 35.2 +/- 10.8 pg/ml, sevenfold greater than those values found in the arterial plasma (P less than 0.01). In six additional dogs, 120 min after unilateral ALI had been induced with ECV (9 mg/kg iv), LTC4 in the bronchoalveolar lavage (BAL) of the uninjured lung was 12.1 +/- 1.5 pg/ml, unchanged from pre-ECV values, whereas, LTC4 in the BAL of the injured lung increased from a control value of 10.2 +/- 1.6 to 24.2 +/- 3.5 pg/ml (P less than 0.01) 120 min after ECV administration. These results demonstrate that, in ECV-induced acute lung injury, LTC4 concentrations in pulmonary edema fluid are considerably greater than those found in arterial plasma in the case of bilateral acute lung injury and significantly greater in the BAL of the injured lung compared with the uninjured lung in the case of unilateral acute lung injury. The results are a necessary first step in support of the hypothesis that leukotrienes participate in the altered permeability of ECV-induced acute lung injury.
D000208:Acute Disease; D000818:Animals; D001784:Blood Gas Analysis; D001834:Body Water / Q000378:metabolism; D004285:Dogs; D004984:Ethchlorvynol; D006439:Hemodynamics; D008168:Lung / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism; D012137:Respiratory System / Q000503:physiopathology; D013189:SRS-A / Q000097:blood / Q000378:metabolism*; D007507:Therapeutic Irrigation
D013189:SRS-A; D004984:Ethchlorvynol