Prevention of exercise-induced bronchoconstriction by inhaled low- molecular-weight heparin

Tahir Ahmed, Brenda J. Gonzalez, Ignacio Danta

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Because many biological actions of heparin including the antiallergic activity are molecular weight dependent, we hypothesized that low-molecular- weight heparin (LMWH) may have greater potency in attenuating exercise- induced bronchoconstriction (EIB). Therefore, in the present investigation we studied the effects of inhaled LMWH, enoxaparin, and unfractionated heparin on EIB in subjects with asthma. Thirteen asthmatic subjects performed a standardized exercise challenge on a treadmill to document the presence of EIB. The workload was increased until 85% of predicted maximal heart rate was achieved, and the exercise was sustained at that workload for 10 min. EIB was assessed by measuring FEV1 before and immediately after the exercise. On five different experiment days the subjects were pretreated with 4 ml of aerosolized heparin (80,000 units = 7.5 mg/kg), placebo, or 3 different doses of enoxaparin (0.5 mg/kg, 1 mg/kg, 2 mg/kg) in a double-blind, randomized, crossover design, and exercise challenge was performed 45 min later. Bronchial provocation with methacholine was also performed in five subjects on two additional days after pretreatment with either placebo or inhaled enoxaparin (2 mg/kg), and venous blood was obtained for analysis of plasma antifactor Xa. Postexercise, the maximal decreases in FEV1 (mean ± SE) were 30 ± 4% and 29 ± 5% on control and placebo days. The exercise-induced decreases in FEV1 were inhibited by 31% with heparin (ΔFEV1 = 20 ± 4%); and by 28%, 38%, and 48% by enoxaparin at doses of 0.5 mg/kg (ΔFEV1 = 21 ± 5%), 1 mg/kg (ΔFEV1 = 18 ± 5%), and 2 mg/kg (ΔFEV1 = 15 ± 3%), respectively (p < 0.05). The inhibitory effect of 0.5 mg/kg dose of enoxaparin was comparable to heparin (7.5 mg/kg), whereas 2 mg/kg dose of enoxaparin was the most potent. Inhaled enoxaparin failed to modify the bronchoconstrictor response to methacholine, and did not change the plasma antifactor Xa activity. These data demonstrate that inhaled enoxaparin prevents EIB in a dose-dependent manner; and its antiasthmatic activity is independent of its effect on plasma antifactor Xa activity.

Original languageEnglish (US)
Pages (from-to)576-581
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Issue number2
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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