Meakins Christie Laboratories, McGill University, Montreal (Qc), Canada.
Respir Res. 2010 Jun 21;11(1):82. doi: 10.1186/1465-9921-11-82.
Pulmonary function has been reported in mice using negative pressure-driven forced expiratory manoeuvres (NPFE) and the forced oscillation technique (FOT). However, both techniques have always been studied using separate cohorts of animals or systems. The objective of this study was to obtain NPFE and FOT measurements at baseline and following bronchoconstriction from a single cohort of mice using a combined system in order to assess both techniques through a refined approach.
Groups of allergen- or sham-challenged ovalbumin-sensitized mice that were either vehicle (saline) or drug (dexamethasone 1 mg/kg ip)-treated were studied. Surgically prepared animals were connected to an extended flexiVent system (SCIREQ Inc., Montreal, Canada) permitting NPFE and FOT measurements. Lung function was assessed concomitantly by both techniques at baseline and following doubling concentrations of aerosolized methacholine (MCh; 31.25 - 250 mg/ml). The effect of the NPFE manoeuvre on respiratory mechanics was also studied.
The expected exaggerated MCh airway response of allergic mice and its inhibition by dexamethasone were detected by both techniques. We observed significant changes in FOT parameters at either the highest (Ers, H) or the two highest (Rrs, RN, G) MCh concentrations. The flow-volume (F-V) curves obtained following NPFE manoeuvres demonstrated similar MCh concentration-dependent changes. A dexamethasone-sensitive decrease in the area under the flow-volume curve at the highest MCh concentration was observed in the allergic mice. Two of the four NPFE parameters calculated from the F-V curves, FEV0.1 and FEF50, also captured the expected changes but only at the highest MCh concentration. Normalization to baseline improved the sensitivity of NPFE parameters at detecting the exaggerated MCh airway response of allergic mice but had minimal impact on FOT responses. Finally, the combination with FOT allowed us to demonstrate that NPFE induced persistent airway closure that was reversible by deep lung inflation.
We conclude that FOT and NPFE can be concurrently assessed in the same cohort of animals to determine airway mechanics and expiratory flow limitation during methacholine responses, and that the combination of the two techniques offers a refined control and an improved reproducibility of the NPFE.
已经有研究报道使用负压驱动呼气法（NPFE）和强迫振荡技术（FOT）来检测小鼠的肺功能。然而，这两种技术一直都是使用单独的动物队列或系统进行研究的。本研究的目的是通过一种改进的方法，从单个小鼠队列中使用联合系统获得 NPFE 和 FOT 测量值，以同时评估这两种技术。
研究了卵清蛋白致敏的变应原或假处理的小鼠，这些动物接受了载体（盐水）或药物（地塞米松 1mg/kg ip）处理。经过手术准备的动物与扩展的 flexiVent 系统（SCIREQ Inc.，蒙特利尔，加拿大）相连，允许进行 NPFE 和 FOT 测量。同时通过这两种技术在基线和雾化乙酰甲胆碱（MCh；31.25-250mg/ml）加倍浓度后评估肺功能。还研究了 NPFE 操作对呼吸力学的影响。
两种技术都检测到变应性小鼠的 MCh 气道反应明显夸大及其被地塞米松抑制。我们观察到在最高（Ers，H）或两个最高（Rrs，RN，G）MCh 浓度时 FOT 参数发生显著变化。在 NPFE 操作后获得的流量-容积（F-V）曲线显示出相似的 MCh 浓度依赖性变化。在变应性小鼠中，在最高 MCh 浓度下，NPFE 后流量-容积曲线下的面积出现了地塞米松敏感的下降。从 F-V 曲线计算的 NPFE 四个参数中的两个，FEV0.1 和 FEF50，也捕捉到了预期的变化，但仅在最高 MCh 浓度下。将 NPFE 参数归一化为基线可以提高检测变应性小鼠夸大的 MCh 气道反应的敏感性，但对 FOT 反应的影响最小。最后，与 FOT 相结合，我们能够证明 NPFE 诱导持续的气道关闭，深肺充气可使其逆转。
我们得出结论，FOT 和 NPFE 可以在同一动物队列中同时进行评估，以确定在乙酰甲胆碱反应期间的气道力学和呼气流量限制，并且这两种技术的结合提供了 NPFE 的精细控制和更好的重现性。
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