A guinea pig model of acute and chronic asthma using permanently instrumented and unrestrained animals

Abstract

To investigate mechanisms underlying allergen-induced asthmatic reactions, airway hyperresponsiveness and remodeling, we have developed a guinea pig model of acute and chronic asthma using unanesthetized, unrestrained animals. To measure airway function, ovalbumin (IgE)-sensitized animals are permanently instrumented with a balloon-catheter, which is implanted inside the pleural cavity and exposed at the neck of the animal. Via an external cannula, the balloon-catheter is connected to a pressure transducer, an amplifier, an A/D converter and a computer system, enabling on-line measurement of pleural pressure (P(pl))-closely correlating with airway resistance-for prolonged periods of time. Using aerosol inhalations, the method has been successfully applied to measure ovalbumin-induced early and late asthmatic reactions and airway hyperresponsiveness. Because airway function can be monitored repeatedly, intra-individual comparisons of airway responses (e.g., to study drug effects) are feasible. Moreover, this model is suitable to investigate chronic asthma and airway remodeling, which occurs after repeated allergen challenges. The protocol for establishing this model takes about 4 weeks.

Guinea pig cysteinyl leukotriene receptor 2 (gpCysLT2) mediates cell proliferation and intracellular calcium mobilization by LTC4 and LTD4

“…Ressmeyer et al showed similar response between human and guinea pig lung slices to LTD4 (17). It may be reflected on the frequent use of the guinea pig as the asthma model and in leukotrienes research (25). Moreover, we revealed that LTC4 and LTD4 had the same potency for cellular proliferation through CysLT2, despite LTC4 having much higher potency for increasing intracellular calcium than LTD4.…”

Using guinea pigs in studies relevant to asthma and COPD

“…1 and 2). Several breakthroughs in measuring lung mechanics were developed first in studies using this species, while models of the late phase response following an allergen challenge have been perfected in guinea pigs [22][23][24][25][26][27]. The emergence of transgenic mouse studies has and will continue to result in the diminished use of guinea pigs for modeling airways disease.…”

“…The emergence of transgenic mouse studies has and will continue to result in the diminished use of guinea pigs for modeling airways disease. This is unfortunate, as for many endpoints guinea pigs are superior to mice for studies of processes related to asthma and COPD [1,[27][28][29]. These advantages as well as the disadvantages of using guinea pigs to study basic processes related to asthma and COPD pathogenesis are briefly reviewed.…”

“…Due to the size of the airways and thus the limited number of cells recoverable from guinea pigs, few studies of muscle proliferation and/or muscle synthesizing activity have been completed in guinea pigs. But smooth muscle hyperplasia has been observed in models of allergic inflammation [27,48]. Airway smooth muscle (and the epithelium) is also a major source of eotaxin in human and guinea pig airways [49,50].…”

“…The guinea pig is thought to be more "eosinophilic" at baseline, as evidenced by the higher percentage of eosinophils recovered by lavage of unchallenged guinea pigs relative to that seen in humans and the presence of eosinophils in cross-sections through airways of seemingly healthy, unchallenged guinea pigs [25][26][27]95,[146][147][148]. This may be due to a constituitive expression of the chemokines eotaxin and CCL5 (RANTES) in the airways of guinea pigs [49,149].…”