Effects of prostacyclin on bronchoconstriction and neutropenia induced by inhaled platelet-activating factor in man.
We studied the effects of prostacyclin (PGI2) on the airway responses to platelet-activating factor (PAF) in a randomized and crossover study in eight normal subjects. PGI2 or diluent (glycine buffer) was continuously infused on 2 separate days. Two breaths of PAF (21 micrograms) were inhaled three times every 15 minutes and airflow at 30% of vital capacity from partial flow-volume curves (Vp30) was measured. PGI2 (4 ng/kg/min) had no effect on Vp30 or blood pressure, whereas heart rate increased from 70.3 +/- 3.9 to 73.7 +/- 4.0 beats/min (mean +/- SEM; p less than 0.01). Two subjects did not complete the study because of transient hypotension. PGI2 had no effect on PAF-induced bronchoconstriction with maximal decreases in Vp30 of 42.0 +/- 8.0% (p less than 0.01) during PGI2 and 49.8 +/- 14.2% (p less than 0.02) during diluent infusion. Ex vivo platelet aggregation to PAF (10(-9) to 10(-7) mol/L) was significantly inhibited by PGI2. Circulating neutrophils decreased from 4.7 +/- 0.9 x 10(9)/L to 1.5 +/- 0.3 x 10(9)/L (p less than 0.05) 5 minutes after the first PAF inhalation during diluent infusion, whereas there was no significant change with PGI2. Thus, PGI2 does not influence PAF-induced bronchoconstriction in man despite causing marked inhibition of ex vivo PAF-induced platelet aggregation and preventing the fall of neutrophils.
Lammers
J W
JW
Department of Thoracic Medicine, Brompton Hospital, London, England.
Kioumis
I
I
McCusker
M
M
Nichol
G M
GM
Barnes
P J
PJ
Chung
K F
KF
D000280:Administration, Inhalation; D000328:Adult; D000380:Agranulocytosis / Q000209:etiology*; D001794:Blood Pressure / Q000187:drug effects; D001986:Bronchial Spasm / Q000097:blood / Q000209:etiology*; D011464:Epoprostenol / Q000494:pharmacology*; D005540:Forced Expiratory Flow Rates / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009503:Neutropenia / Q000209:etiology*; D009504:Neutrophils / Q000187:drug effects; D010972:Platelet Activating Factor / Q000008:administration & dosage*; D010974:Platelet Aggregation / Q000187:drug effects; D011897:Random Allocation
D010972:Platelet Activating Factor; D011464:Epoprostenol