Hexamethylene diisocyanate (HDI)-induced lung impairment: studies in isolated perfused and ventilated guinea pig lungs.
Isolated, perfused and ventilated guinea pig lungs were exposed to hexamethylene diisocyanate via the air passages. Two air concentrations of hexamethylene diisocyanate were studied (3.5 and 11 mg/m3). There was a statistically significant (P < 0.05-0.001) dose-related reduction in both conductance and compliance but no effects were noted on the pulmonary circulation. With 3.5 mg/m3 hexamethylene diisocyanate the conductance capacity was reduced with 38% and compliance with 30% after 60 min. exposure. Eleven mg/m3 hexamethylene diisocyanate reduced the conductance and compliance capacity with 86 and 69%, respectively, on an average. The reduction in lung function (with 11 mg/m3) was abolished when 100 microM diclofenac, a cyclooxygenase inhibitor, was added to the perfusate (P < 0.01). The thromboxane A2 antagonist L-670, 596 (20 microM) exerted a partial protective effect. The capacity of conductance and compliance decreased with 46 and 32%, respectively, on an average, after preperfusion with L-670, 596 and a following exposure of 11 mg/m3 hexamethylene diisocyanate for 60 min. Statistically significant 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 ventilated guinea pig lungs.
Låstbom
L
L
Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
Skarping
G
G
Moldéus
P
P
Ryrfeldt
A
A
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D016084:Bronchoconstriction / Q000187:drug effects; D003485:Cyanates / Q000633:toxicity*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D017953:Isocyanates; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008170:Lung Compliance / Q000187:drug effects*; D008297:Male; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects*; D012123:Pulmonary Ventilation; D013931:Thromboxanes / Q000378:metabolism
D003485:Cyanates; D016861:Cyclooxygenase Inhibitors; D017953:Isocyanates; D013931:Thromboxanes; C015262:1,6-hexamethylene diisocyanate; D004008:Diclofenac; D016718:Arachidonic Acid