HEXAMETHYLENE DIISOCYANATE (HDI)-INDUCED LUNG IMPAIRMENT - STUDIES INISOLATED-PERFUSED AND VENTILATED GUINEA-PIG LUNGS

Isolated, perfused and ventilated guinea pig lungs were exposed to hex amethylene diisocyanate via the air passages. Two air concentrations o f hexamethylene diisocyanate were studied (3.5 and 11 mg/m(3)). There was a statistically significant (P<0.05 - 0.001) dose-related reductio n in both conductance and compliance but no effects were noted on the pulmonary circulation. With 3.5 mg/m(3) hexamethylene diisocyanate the conductance capacity was reduced with 38 % and compliance with 30 % a fter 60 min. exposure. Eleven mg/m(3) hexamethylene diisocyanate reduc ed the conductance and compliance capacity with 86 and 69 %, respectiv ely, on an average. The reduction in lung function (with 11 mg/m(3)) w as abolished when 100 mu M diclofenac, a cyclooxygenase inhibitor, was added to the perfusate (P<0.01). The thromboxane Az antagonist L-670, 596 (20 mu M) exerted a partial protective effect. The capacity of con ductance and compliance decreased with 46 and 32 % respectively, on an average, after preperfusion with L-670,596 and a following exposure o f 11 mg/m(3) hexamethylene diisocyanate for 60 min. Statistically sign ificant protection (P<0.05) was obtained on compliance and the P-value was<0.1 for conductance. Thus, these data indicate that hexamethylene diisocyanate-induced bronchoconstriction is mediated via arachidonic acid release and thromboxane formation, in isolated, perfused and vent ilated guinea pig lungs.