Am. J. Respir. Crit. Care Med.,
Volume 160, Number 2, August 1999, 576-581
Prevention of Exercise-induced Bronchoconstriction
by Inhaled Low-molecular-weight Heparin
TAHIR
AHMED,
BRENDA J.
GONZALEZ,
and
IGNACIO
DANTA
Division of Pulmonary Disease, University of Miami School of Medicine, Mount Sinai Medical Center, Miami Beach, Florida
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 (
FEV1 = 20 ± 4%); and by 28%, 38%, and 48% by enoxaparin at doses of 0.5 mg/kg (FEV1 = 21 ± 5%), 1 mg/kg (FEV1 = 18 ± 5%), and 2 mg/kg (FEV1 = 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.
