title: Platelet-activating factor causes ventilation-perfusion mismatch in humans.
abstract: We hypothesized that platelet-activating factor (PAF), a potent inflammatory mediator, could induce gas exchange abnormalities in normal humans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation-perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1 [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased systemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial-alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF, because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04), respectively. We conclude that in normal subjects, inhaled PAF results in considerable immediate VA/Q inequality and gas exchange impairment. These results reinforce the notion that PAF may play a major role as a mediator of inflammation in the human lung.
authors.affiliation: Servei de Pneumologia i Al.lèrgia Respiratòria, Hospital Clínic, Facultat de Medicina, Universitat de Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Rodriguez-Roisin
authors.forename: M A
authors.initials: MA
authors.lastname: Félez
authors.forename: K F
authors.initials: KF
authors.lastname: Chung
authors.forename: J A
authors.initials: JA
authors.lastname: Barberà
authors.forename: P D
authors.initials: PD
authors.lastname: Wagner
authors.forename: A
authors.initials: A
authors.lastname: Cobos
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: J
authors.initials: J
authors.lastname: Roca
mesh_terms: D000293:Adolescent; D000328:Adult; D000336:Aerosols; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects*; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D000336:Aerosols; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D010100:Oxygen