Measurement of lung function in rodents in vivo
Examination of pulmonary function is a nondestructive procedure of assessing the functional consequences of alterations of lung structure or (temporary) changes in the tonus of airway smooth muscle cells, providing information on the presence, the type and the extent of alteration. The principles governing ventilation, air flow, lung volume and gas exchange are common among most if not all mammals . There is a considerable quantity of literature describing the methodology, physiological principles and typical values of lung function tests in man and experimental animals. Reviews of the methods used for rodents have been presented by Mauderly and Likens [10,12], Costa and Tepper  and Murphy . The tests used at present are the result or unique adaptions of clinical lung function tests to small animals. In this chapter we will present methods of noninvasive pulmonary function measurement in rodents in our laboratories and we will present typical examples of their use. Our main working fields are the preclinical evaluation of drug using nonallergic and allergic asthma models, lung function tests to assess and to monitor lung alterations in inhalation studies (e.g. in legally prescribed toxicity tests) and the investigation of pulmonary diseases (e.g. fibrosis, asthma or organ rejection after lung transplantation). These studies can be performed according to the guidelines of Good Laboratory Practice (GLP). Conscious guinea pigs are used in preclinical efficacy studies, primarily in asthma studies. The experimental design of this model is relatively simple so that four animals can be examined at the same time. The disadvantages are that movement artifacts sometimes disturb the measurement and that only a few spontaneous respiration parameters can be measured. Therefore, in toxicological and some of the pharmacological questions not enough end points and sensitivity are avalable. In anaesthetised rats, the whole range of lung function tests available in the cli nic can be performed. This animal model is thus used in preclinical studies as an asthma model, in safety pharmacology and toxicity studies when more end points and a higher resolution of measurement are needed (extended lung function). The methodology of noninvasive pulmonary function measurement in the anaesthetised rat [6,8,9] is based mainly on methods reported by Likens and Mauderly . Anaethesia permits measurement of lung compliance and resistance and yields the ability to perform involuntary breathing manoeuvres to achieve and extended functional characterisation (e.g. by force d expiratory flow-volume curve or quasistatic manoeuvre.) The lung function tests can be performed before and after treatment and/or challenge of the animal (e. g. as an asthma model) all on the same occasion or in different phases of a study ( used in long-term studies). To test of nonspecific bronchoplasmolytic potency of drugs or as a hyperreactivity test, an acetylcholine challenge can be perform e d, which is a useful bronchial provocation test for small rodents. As a model for allergic asthma, the animal can be sensitised (by ovalbumin) and challenge by the respective antigen.