PLATELET-ACTIVATING-FACTOR CAUSES VENTILATION-PERFUSION MISMATCH IN HUMANS

We hypothesized that platelet-activating factor (PAF), a potent inflam matory mediator, could induce gas exchange abnormalities in normal hum ans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 mu g) on ventilation-perfusion (V-A/Q) relationships, hemodynamics, an d resistance of the respiratory system was studied in 14 healthy, nona topic, 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 inhal ed lyso-PAF in 10 other healthy individuals (24+/-2 yr) PAF induced, c ompared to lyso-PAF, immediate leukopenia(P < 0.001) followed by a reb ound leukocytosis (P+/-0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased sy stemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, Pa-O2 showed a trend to fall (by 12.2+/-4.3 mmHg, mean+/-SEM maximum c hange from baseline), and arterial-alveolar O-2 gradient increased(by 16.7+/-4.3 mmHg) (P < 0.02) after PAF, because of V-A/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased b y 0.45+/-0.1 (P < 0.01) and 0.29+/-0.1 (P < 0.04), respectively. We co nclude that in normal subjects, inhaled PAF results in considerable im mediate V-A/Q inequality and gas exchange impairment. These results re inforce the notion that PAF may play a major role as a mediator of inf lammation in the human lung.