Platelet-activating Factor Causes Ventilation-Perfusion Mismatch in Humans

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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 (VdotA/Qdot) 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 VdotA/Qdot 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 VdotA/Qdot 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. (J. Clin. Invest. 1994. 93:188-194.) Key words: airway microvascular permeability. asthma. inflammatory mediators. pulmonary gas exchange. pulmonary hemodynamics and mechanics

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