Abstract
Unfractionated heparin (UF-heparin) has been shown to prevent antigen- induced airway hyperresponsiveness (AHR), but tt is ineffective when administered after the antigen challenge. We hypothesized that the failure of UF-heparin to modify postantigen AHR might depend on molecular weight. We therefore studied the effects of UF-heparin and three low-molecular-weight heparin fractions (medium-molecular-weight heparin [MMWH]; low-molecular- weight heparin [LMWH]; and ultralow-molecular-weight heparin [ULMWH]) on antigen-induced AHR and histamine release in bronchoalveolar lavage fluid (BALF). Specific lung resistance (SRL) was measured in 20 allergic sheep before, immediately after, and up to 2 h after challenge with Ascaris suum antigen. Airway responsiveness was expressed as the cumulative provocative dose of carbachol, in breath units, that increased SRL by 400% (PD400). PD400 was determined before and 2 h after antigen, both without and after treatment with aerosolized UF-heparin (1,000 U/kg) and various heparin fractions (0.04 mg/kg to 5 mg/kg) administered after the antigen challenge. Inhaled UF-heparin (n = 4), MMWH (n = 4), and LMWH (n = 6) failed to modify postantigen AHR when administered after the challenge. Only ULMWH (n = 6) inhibited postantigen AHR in a dose-dependent manner (percent protection ranged from 31% to 139%). In eight additional sheep, histamine in BALF was measured with a radioimmunoassay (RIA) before and after the segmental antigen challenge, without and after pretreatment with inhaled UF-heparin, LMWH, or ULMWH. Inhaled UF-heparin and LMWH inhibited antigen-induced histamine release as measured in BALF by 81% and 75%, respectively;, whereas ULMWH was ineffective in this respect. We conclude that: (1) modification of antigen- induced AHR by fractionated heparins is molecular-weight dependent; and (2) only ULMWH attenuates AHR when administered after antigen challenge, via an unknown mast-cell-independent action.
Original language | English (US) |
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Pages (from-to) | 887-893 |
Number of pages | 7 |
Journal | American journal of respiratory and critical care medicine |
Volume | 157 |
Issue number | 3 PART I |
DOIs | |
State | Published - 1998 |
Externally published | Yes |
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine