Perkowski S Z, Havill A M, Flynn J T, Gee M H
Circ Res. 1983 Nov;53(5):574-83. doi: 10.1161/01.res.53.5.574.
In 30 anesthetized sheep, we show that repeated bolus injections of autologous zymosan-activated plasma produce pulmonary hypertension, hypoxemia, intrapulmonary thromboxane release, pulmonary leukostasis, and sustained increases in lung lymph flow and protein clearance. Studies with platelet-rich plasma demonstrated that addition of zymosan-activated plasma does not induce platelet aggregation or thromboxane release. We studied the role of cyclooxygenase products as mediators of these pathophysiological responses by pretreating sheep with either meclofenamate (4 mg/kg) or ibuprofen (12.5 mg/kg). Both drugs inhibited thromboxane release and hypoxemia. Ibuprofen, but not meclofenamate, reproducibly attenuated the hypertensive responses and the increases in lymph flow and protein clearance. Neither drug prevented pulmonary leukostasis. These results demonstrate that cyclooxygenase products mediate the development of complement-induced hypoxemia but are not sole mediators of pulmonary hypertension or increases in vascular permeability. Furthermore, ibuprofen has anti-inflammatory actions, not shared by meclofenamate, which enhance the effectiveness of this drug. Since activated leukocytes release reactive oxygen metabolites, we treated sheep with superoxide dismutase (2800 U/kg per hour) to determine the role of superoxide anions in these responses. This treatment significantly attenuated the increases in lung lymph flow and protein clearance. The results suggest that multiple mediators, which may originate from activated leukocytes sequestered in the pulmonary circulation, contribute to the pathophysiological changes seen with intermittent complement activation. Cyclooxygenase products of arachidonic acid contribute to the hypertension and are solely responsible for the hypoxemia. Reactive oxygen metabolites are important mediators of the complement-induced increases in lung vascular permeability.
在30只麻醉的绵羊中，我们发现反复推注自体酵母聚糖激活血浆会导致肺动脉高压、低氧血症、肺内血栓素释放、肺白细胞淤滞，以及肺淋巴流量和蛋白质清除率持续增加。富含血小板血浆的研究表明，添加酵母聚糖激活血浆不会诱导血小板聚集或血栓素释放。我们通过用甲氯芬那酸（4mg/kg）或布洛芬（12.5mg/kg）预处理绵羊，研究了环氧化酶产物作为这些病理生理反应介质的作用。两种药物均抑制血栓素释放和低氧血症。布洛芬可重复性地减轻高血压反应以及淋巴流量和蛋白质清除率的增加，但甲氯芬那酸则不能。两种药物均不能预防肺白细胞淤滞。这些结果表明，环氧化酶产物介导补体诱导的低氧血症的发生，但不是肺动脉高压或血管通透性增加的唯一介质。此外，布洛芬具有甲氯芬那酸所没有的抗炎作用，这增强了该药物的有效性。由于活化的白细胞会释放活性氧代谢产物，我们用超氧化物歧化酶（每小时2800U/kg）治疗绵羊，以确定超氧阴离子在这些反应中的作用。这种治疗显著减轻了肺淋巴流量和蛋白质清除率的增加。结果表明，多种介质可能源自肺循环中滞留的活化白细胞，它们促成了间歇性补体激活时出现的病理生理变化。花生四烯酸的环氧化酶产物促成高血压，且是低氧血症的唯一原因。活性氧代谢产物是补体诱导的肺血管通透性增加重要介质。
