Rodriguez-Roisin R, Félez M A, Chung K F, Barberà J A, Wagner P D, Cobos A, Barnes P J, Roca J
Servei de Pneumologia i Al.lèrgia Respiratòria, Hospital Clínic, Facultat de Medicina, Universitat de Barcelona, Spain.
J Clin Invest. 1994 Jan;93(1):188-94. doi: 10.1172/JCI116944.
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.
我们推测，强效炎症介质血小板活化因子（PAF）可在正常人体内诱发气体交换异常。为此，我们对14名健康、无特应性且不吸烟的个体（23±1[标准误]岁）在吸入雾化PAF（2mg/ml溶液；24μg）前以及吸入后2、4、6、8、15和45分钟时的通气-灌注（VA/Q）关系、血流动力学和呼吸系统阻力进行了研究，并与另外10名健康个体（24±2岁）吸入溶血PAF后的情况进行了比较。与溶血PAF相比，PAF诱发了即刻白细胞减少（P<0.001），随后出现白细胞增多反弹（P<0.002），增加了分钟通气量（P<0.05）和呼吸系统阻力（P<0.01），并降低了体循环动脉压（P<0.05）。同样，与溶血PAF相比，PAF吸入后，由于VA/Q不匹配，PaO2呈下降趋势（从基线最大变化为12.2±4.3mmHg，均值±标准误），动脉-肺泡氧梯度增加（16.7±4.3mmHg）（P<0.02）：肺血流和通气的离散度分别增加了0.45±0.1（P<0.01）和0.29±0.1（P<0.04）。我们得出结论，在正常受试者中，吸入PAF会导致相当程度的即刻VA/Q不均等和气体交换受损。这些结果强化了PAF可能在人类肺部炎症介导中起主要作用这一观点。
