Inhibition of antigen-induced airway and cutaneous responses by heparin: a pharmacodynamic study.
We have previously shown that heparin attenuates the acute bronchoconstrictor response and immediate cutaneous reaction (ICR) to antigen in allergic sheep. In the present investigation, we studied the pharmacodynamics of the antiallergic action of heparin. Specific lung resistance (sRL) was measured in eight sheep, allergic to Ascaris suum antigen, before and 5 min after inhalation challenge with the antigen. On different experiment days, antigen challenge was repeated after pretreatment with 1) aerosol heparin (1,000 U/kg) administered < or = 20 min, 6 h, 12 h, and 24 h and 2) intravenous heparin (1,000 U/kg) administered < or = 20 min, 1 h, 6 h, and 12 h before antigen challenge. sRL increased by 374 +/- 116% (SE) above baseline with antigen alone. Both aerosol and intravenous heparin attenuated the antigen effects on sRL in a time-dependent fashion. Prolonging the lag time between pretreatment and antigen challenge decreased the inhibitory effect of aerosol heparin; delta sRL was 31 +/- 29, 99 +/- 38, 142 +/- 40, and 306 +/- 60% for < or = 20-min, 6-h, 12-h, and 24-h pretreatment protocols, respectively. In contrast, prolonging the lag time increased the inhibitory effect of intravenous heparin: delta sRL was 246 +/- 64, 66 +/- 26, and 76 +/- 32% for < or = 20 min, 1 h, and 6 h, respectively. In seven additional sheep pretreatment with intravenous heparin (1,000 U/kg) attenuated the ICR also in a time-dependent manner; the inhibitory effect of heparin on ICR to antigen was enhanced 60% by increasing the heparin pretreatment interval from 20 to 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Ahmed
T
T
Division of Pulmonary Disease, University of Miami School of Medicine, Mount Sinai Medical Center, Miami Beach, Florida 33140.
Syriste
T
T
Lucio
J
J
Abraham
W
W
Robinson
M
M
D'Brot
J
J
D000336:Aerosols; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage; D017165:Ascaris suum / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects*; D015550:Cell Degranulation / Q000187:drug effects; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000517:prevention & control*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep
D000336:Aerosols; D000947:Antigens, Helminth; D006493:Heparin