title: Hexamethylene diisocyanate (HDI)-induced lung impairment: studies in isolated perfused and ventilated guinea pig lungs.
abstract: 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.
authors.affiliation: Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Låstbom
authors.forename: G
authors.initials: G
authors.lastname: Skarping
authors.forename: P
authors.initials: P
authors.lastname: Moldéus
authors.forename: A
authors.initials: A
authors.lastname: Ryrfeldt
mesh_terms: 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
chemical_list: D003485:Cyanates; D016861:Cyclooxygenase Inhibitors; D017953:Isocyanates; D013931:Thromboxanes; C015262:1,6-hexamethylene diisocyanate; D004008:Diclofenac; D016718:Arachidonic Acid