Invasive and noninvasive lung function measurements in rodents

Invasive and noninvasive lung function measurements in rodents
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DOI:
10.1016/j.vascn.2006.04.006
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发表时间:
2007-01-01
影响因子:
1.9
通讯作者:
Hoymann, Heinz Gerd
Hoymann, Heinz Gerd
中科院分区:
医学4区
文献类型:
--
作者:
Hoymann, Heinz Gerd

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在完整小鼠或大鼠中精确和可重复的肺功能测量对于各种呼吸系统疾病如哮喘的实验研究以及药物或化学品的药理学、安全药理学或毒理学测试变得越来越重要。本文综述了典型的在体测量技术的简要概述,讨论了它们的优点和缺点,并详细介绍了其中两种方法:非侵入性头外体体积描记法和侵入性但可重复的体体积描记法在口腔气管插管啮齿动物。将证明这些方法能够在安全性药理学试验或哮喘模型中监测支气管收缩,哮喘模型显示对吸入过敏原的早期过敏反应或晚期气道高反应性,并证明药物对肺部终点的影响。在相同的动物中测量了典型支气管收缩模型中相应参数的变化,如潮气中呼气流量(EF50)或肺阻力,并进行了比较以进行验证。它的结论是,侵入性和非侵入性肺功能测试能够检测过敏原特异性以及非过敏性支气管收缩在完整的小鼠或大鼠。有创性耐药测定灵敏度上级,而非侵入性EF 50方法特别适合于快速和可重复地筛选大量小鼠和大鼠的呼吸功能,或者如果必须测试清醒的动物,(如安全药理学)。过去数年,在多项研究中使用这两种方法,证明它们提供了有用和必要的资料,呼吸系统疾病研究中的肺力学,包括哮喘实验模型,小鼠和大鼠的肺药理学、安全药理学和毒理学研究。(c)2006年爱思唯尔公司All rights reserved.
Precise and repeatable measurements of pulmonary function in intact mice or rats are becoming increasingly important for experimental investigations on various respiratory disorders like asthma and for pharmacological, safety-pharmacological or toxicological testing of drugs or chemicals. This review provides a short overview of typical in-vivo measurement techniques, discusses their advantages and disadvantages and presents two of these methods in detail: the noninvasive head-out body plethysmography and an invasive but repeatable body-plethysmography in orotracheally intubated rodents. It will be demonstrated that these methods are able to monitor bronchoconstriction in safety-pharmacological tests or in asthma models showing early allergic response or late airway hyperresponsiveness in response to inhaled allergens and demonstrate drug effects on pulmonary endpoints. The changes in the respective parameters such as tidal midexpiratory flow (EF50) or lung resistance in typical bronchoconstriction models have been measured in the same animals and compared for validation purposes. It is concluded that both invasive and noninvasive pulmonary function tests are capable of detecting allergen-specific as well as non-allergic bronchoconstriction in intact mice or rats. The invasive determination of resistance is superior in sensitivity, whereas the noninvasive EF50 method is particularly appropriate for quick and repeatable screening of respiratory function in large numbers of mice and rats or if the conscious animal has to be tested (e.g. safety pharmacology).The use of both techniques in a large number of studies in the last years have demonstrated that they provide useful and necessary information on pulmonary mechanics in studies of respiratory disorders including experimental models of asthma, in investigations of pulmonary pharmacology, safety pharmacology and toxicology in mice and rats. (c) 2006 Elsevier Inc. All rights reserved.