title: Hexamethylene diisocyanate induction of transient airway hyperresponsiveness in guinea pigs.
abstract: The induction of lung injury and the development of airway hyperresponsiveness (AHR) by exposure to hexamethylene diisocyanate (HDI) were studied in a guinea pig model of occupational lung diseases. In addition to an unexposed control group of 16 guinea pigs (A), two groups (B, C) of 8 animals inhaled HDI atmospheres in the range of the threshold limit value (TLV) of 10 ppb for 6 h/day on 5 days/week over a period of 8 weeks. Airway responses to aerosols of 0.125, 0.25, 0.5, 1.0 and 2.0% acetylcholine (ACH) were measured in exposed as well as in unexposed animals. Basal values of respiratory mechanical and cardiovascular parameters were not significantly altered after 8 weeks of HDI inhalation (group B). Furthermore, additional acute challenge by 10 ppb HDI for a period of 60 min, performed under continuous registration of respiratory and cardiovascular parameters, did not cause any significant changes in functional parameters. After 8 weeks of HDI exposure, the amplitude of airway constriction as a response to 2.0% ACH, indicated by the changes in dynamic elastance (Edyn) rose significantly to almost 5 times the ACH response in group A(p < 0.0005). In group C of 8 guinea pigs, ACH response was evaluated after a latency period of 8 weeks. In this group, changes of airway responsiveness to ACH were significantly smaller than in group B without a latency period. They were comparable to those of group A. In summary, HDI-induced airway hyperresponsiveness to ACH in the guinea pig is reversible within 8 weeks of HDI avoidance. It is assumed that the augmented airway responsiveness indicates an increased risk of developing isocyanate-induced obstructive lung diseases.
authors.affiliation: Professional Associations' Research Institute for Occupational Medicine (BGFA), Ruhr University, Bochum, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Marek
authors.forename: T
authors.initials: T
authors.lastname: Mensing
authors.forename: F
authors.initials: F
authors.lastname: Riedel
authors.forename: N
authors.initials: N
authors.lastname: Viso
authors.forename: B
authors.initials: B
authors.lastname: Marczynski
authors.forename: X
authors.initials: X
authors.lastname: Baur
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000633:toxicity; D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000503:physiopathology; D003485:Cyanates / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D017953:Isocyanates; D008173:Lung Diseases, Obstructive / Q000139:chemically induced; D008452:Maximum Allowable Concentration; D009784:Occupational Diseases / Q000139:chemically induced; D012075:Remission, Spontaneous; D012129:Respiratory Function Tests
chemical_list: D000336:Aerosols; D003485:Cyanates; D017953:Isocyanates; C015262:1,6-hexamethylene diisocyanate; D000109:Acetylcholine