Lewis C A, Raeburn D, Broadley K J
Pharmacology Department Welsh School of Pharmacy, University of Wales Cardiff, UK.
Pulm Pharmacol. 1994 Oct;7(5):311-7. doi: 10.1006/pulp.1994.1037.
Airway hyperreactivity to physical, chemical, immunological and pharmacological stimuli is well documented in vivo. The aim of this study was to investigate whether tissues taken from guinea-pigs that had been shown to display hyperreactivity in vivo after antigen challenge were also hyperreactive in vitro. Isolated airway-perfused lungs from ovalbumin-sensitized guinea-pigs challenged 24 h beforehand with an aerosol of ovalbumin showed a significant (P < 0.05) increase in responsiveness to the bronchoconstrictor response to a bolus dose of carbachol (10 micrograms) when compared with saline challenged animals. The contractile responses to single doses of carbachol (10 micrograms) and histamine (30 micrograms) in immersed tracheal spiral preparations taken from sensitized animals exposed to the ovalbumin were also significantly enhanced (P < 0.05). A non-significant leftward shift was observed in the concentration-response curve for histamine in challenged perfused lungs from ovalbumin-challenged animals compared with an NaCl challenge. Concentration-response curves to carbachol and histamine in immersed tracheal spirals were virtually superimposed. Therefore, this study has shown non-specific airway hyperreactivity of isolated airway perfused lungs at 24 h following a challenge of sensitized guinea-pigs with aerosolized ovalbumin, although this was not evident from concentration-response curves in immersed trachea. The isolated perfused lung therefore provides a simple method for further evaluation of the mechanisms of airway hyperreactivity.
气道对物理、化学、免疫和药理刺激的高反应性在体内已有充分记录。本研究的目的是调查从经抗原激发后在体内显示出高反应性的豚鼠身上获取的组织在体外是否也具有高反应性。来自预先用卵清蛋白气雾剂激发24小时的卵清蛋白致敏豚鼠的离体气道灌注肺,与用盐水激发的动物相比,对大剂量卡巴胆碱(10微克)的支气管收缩反应的反应性显著增加(P < 0.05)。从暴露于卵清蛋白的致敏动物身上获取的浸入式气管螺旋制剂对单剂量卡巴胆碱(10微克)和组胺(30微克)的收缩反应也显著增强(P < 0.05)。与用氯化钠激发相比,在来自卵清蛋白激发动物的激发灌注肺中,组胺的浓度 - 反应曲线观察到非显著的左移。浸入式气管螺旋中对卡巴胆碱和组胺的浓度 - 反应曲线几乎重叠。因此,本研究表明,在用雾化卵清蛋白激发致敏豚鼠24小时后,离体气道灌注肺具有非特异性气道高反应性,尽管这在浸入式气管的浓度 - 反应曲线中并不明显。因此,离体灌注肺为进一步评估气道高反应性的机制提供了一种简单的方法。