Am. J. Respir. Crit. Care Med., Volume 165, Number 1, January 2002, 27-33

Heparin Inhibits Hyperventilation-Induced Late-Phase Hyperreactivity in Dogs

RYOICHI SUZUKI and ARTHUR N. FREED

Department of Environmental Health Sciences, The Johns Hopkins School of Public Health, Baltimore, Maryland

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 (RP) to aerosol and intravenous histamine before and 5 h after DAC. Bronchoalveolar lavage fluid (BALF) cells and eicosanoid mediators were also measured ~ 5 h after DAC. DAC of vehicle-treated bronchi resulted in late-phase airway obstruction (~ 120% increase over baseline RP), inflammation, increased BALF concentrations of leukotriene (LT) C₄, LTD₄, and LTE₄ and prostaglandin (PG)D₂, and AHR. Pretreatment with aerosolized heparin attenuated late-phase airway obstruction by ~ 50%, inhibited eosinophil infiltration, reduced BALF concentrations of LTC₄, LTD₄, and LTE₄ and PGD₂, 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.

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