Heparin inhibits eicosaniod metabolism and hyperventilation-induced bronchoconstriction in dogs

Citation
R. Suzuki et An. Freed, Heparin inhibits eicosaniod metabolism and hyperventilation-induced bronchoconstriction in dogs, AM J R CRIT, 161(6), 2000, pp. 1850-1854
Citations number
47
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","da verificare
Journal title
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
ISSN journal
1073-449X → ACNP
Volume
161
Issue
6
Year of publication
2000
Pages
1850 - 1854
Database
ISI
SICI code
1073-449X(200006)161:6<1850:HIEMAH>2.0.ZU;2-D
Abstract
Inhalation of heparin, an anticoagulant, attenuates exercise-induced asthma (EIA) in human subjects. The purpose of this study was to determine if hep arin inhibits hyperventilation-induced bronchoconstriction (HIB) in a canin e model of EIA, and if its mode of action involves the inhibition of eicosa noid mediator production and release. We used a wedged bronchoscope techniq ue 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% CO2 in air used to ventilate a wedg ed sublobar segment. We compared HIB before and 60 min after aerosol treatm ent with either bacteriostatic water (BW) or heparin. We found that (1) hep arin had no effect on baseline Rp, (2) BW did not alter the response to DAC , and (3) heparin reduced HIB by similar to 50-60%. On the basis of broncho alveolar ravage fluid (BALF) cell analysis, heparin and BW caused acute inf iltration of macrophages and eosinophils, and heparin increased the number of erythrocytes recovered immediately after DAC. Despite these acute inflam matory 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 signifi cantly attenuates HIB.