Heparin inhibits eicosanoid metabolism and hyperventilation-induced bronchoconstriction in dogs.
Inhalation of heparin, an anticoagulant, attenuates exercise- induced asthma (EIA) in human subjects. The purpose of this study was to determine if heparin inhibits hyperventilation-induced bronchoconstriction (HIB) in a canine model of EIA, and if its mode of action involves the inhibition of eicosanoid mediator production and release. We used a wedged bronchoscope technique to measure baseline peripheral airway resistance (Rp). We then performed either a 2-min or 5-min dry air challenge (DAC) by temporarily increasing from 200 to 2,000 ml/min the flow of 5% CO(2) in air used to ventilate a wedged sublobar segment. We compared HIB before and 60 min after aerosol treatment with either bacteriostatic water (BW) or heparin. We found that (1) heparin had no effect on baseline Rp, (2) BW did not alter the response to DAC, and (3) heparin reduced HIB by approximately 50-60%. On the basis of bronchoalveolar lavage fluid (BALF) cell analysis, heparin and BW caused acute infiltration of macrophages and eosinophils, and heparin increased the number of erythrocytes recovered immediately after DAC. Despite these acute inflammatory effects initiated prior to DAC, BALF mediator analyses revealed that pretreatment with heparin either attenuated or abolished hyperventilation-induced leukotriene, prostaglandin, and thromboxane release. Thus, our data provide direct evidence that inhaled heparin inhibits eicosanoid mediator production and release caused by hyperventilation with dry air, and significantly attenuates HIB.
Suzuki
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Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
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D000280:Administration, Inhalation; D000403:Airway Resistance / Q000276:immunology; D000818:Animals; D001250:Asthma, Exercise-Induced / Q000276:immunology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000276:immunology*; D004285:Dogs; D015777:Eicosanoids / Q000378:metabolism*; D004906:Erythrocyte Count; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D006985:Hyperventilation / Q000276:immunology*; D007958:Leukocyte Count; D015289:Leukotrienes / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism
D015777:Eicosanoids; D015289:Leukotrienes; D011453:Prostaglandins; D013931:Thromboxanes; D006493:Heparin