title: Heparin inhibits hyperventilation-induced late-phase hyperreactivity in dogs.
abstract: Inhalation of heparin attenuates hyperventilation-induced bronchoconstriction in humans and dogs. The purpose of this study was to determine whether heparin inhibits the late-phase response to hyperventilation, which is characterized by increased peripheral airway resistance (RP), eicosanoid mediator production, neutrophilic/ eosinophilic inflammation, and airway hyperreactivity (AHR) at 5 h after dry air challenge (DAC). Fiberoptic bronchoscopy was used to record RP and airway reactivity (DeltaRP) to aerosol and intravenous histamine before and 5 h after DAC. Bronchoalveolar lavage fluid (BALF) cells and eicosanoid mediators were also measured approximately 5 h after DAC. DAC of vehicle-treated bronchi resulted in late-phase airway obstruction (approximately 120% increase over baseline RP), inflammation, increased BALF concentrations of leukotriene (LT) C(4), LTD(4), and LTE(4) and prostaglandin (PG)D(2), and AHR. Pretreatment with aerosolized heparin attenuated late-phase airway obstruction by approximately 50%, inhibited eosinophil infiltration, reduced BALF concentrations of LTC(4), LTD(4), and LTE(4) and PGD(2), and abolished AHR. We conclude that heparin inhibits hyperventilation-induced late-phase changes in peripheral airway function, and does so in part via the inhibition of eosinophil migration and eicosanoid mediator production and release.
authors.affiliation: Department of Environmental Health Sciences, The Johns Hopkins School of Public Health, Baltimore, Maryland 20892-7924, USA.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Suzuki
authors.forename: Arthur N
authors.initials: AN
authors.lastname: Freed
mesh_terms: D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001999:Bronchoscopy; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D015777:Eicosanoids / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006985:Hyperventilation / Q000150:complications* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation; D017997:Leukotriene C4 / Q000032:analysis; D017998:Leukotriene D4 / Q000032:analysis; D017999:Leukotriene E4 / Q000032:analysis; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D015230:Prostaglandin D2 / Q000032:analysis; D013997:Time Factors
chemical_list: D015777:Eicosanoids; D017997:Leukotriene C4; D017998:Leukotriene D4; D017999:Leukotriene E4; D006493:Heparin; D015230:Prostaglandin D2