SALBUTAMOL INHIBITS PULMONARY EFFECTS OF PLATELET-ACTIVATING-FACTOR IN MAN

Inhaled platelet-activating factor (PAF) provokes considerable pulmona ry gas exchange disturbances in normal man and in patients with mild a sthma, similar to those observed in acute severe asthma. To further ex amine the mechanisms involved in PAF-induced ventilation-perfusion (VA /Q) mismatch, eight healthy, non-atopic, nonsmoking subjects were stud ied after administration of PAF aerosol (24 mu g). They had been previ ously treated with inhaled salbutamol (300 mu g) in a randomized, doub le-blind, cross-over, placebo-controlled design. After placebo, PAF pr ovoked a fall in total arterial white cell count with a rebound leukoc ytosis. As shown in a previous study, an overall index of VA/Q inequal ity (DISP R-E 1.64 +/- 0.10) showed a threefold increase (p < 0.006) that accounted for the increase (79%) in AaPO(2) (p < 0.04) after PAF, while the respiratory system resistance (Pm) rose by 16% (p < 0.02). In contrast, after pretreatment with salbutamol inhaled PAF had no eff ects on pulmonary gas exchange, Pm, or white cell count; facial flushi ng and cough were also hindered. The results are consistent with the h ypothesis that salbutamol inhibits PAF-induced venoconstriction in bot h the airway and pulmonary microcirculation.