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

Nature Protocols volume 1, pages 840–847 (2006)Cite this article

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 (Ppl)—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.

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Figure 1: Experimental setup.
Figure 2: Allergen-induced early and late asthmatic reactions and airway hyperresponsiveness.
Figure 3: Bronchoalveolar lavage (BAL) cell counts at 25 h after single saline or ovalbumin (OA) challenge.
Figure 4: Representative histological photomicrographs of formalin-fixed paraffin-embedded lung sections containing transverse cross-sections of peripheral airways, obtained (a) after single saline challenge or (b) after single OA challenge, at 17 h after the challenges.
Figure 5: Airway smooth muscle remodeling after chronic allergen exposure.

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Acknowledgements

The development of these protocols, as well as several in vivo and ex vivo applications, have been financially supported by the Netherlands Asthma Foundation. W.C. Oosterom, F. Brouwer, W.J. Jonker, R. Gosens, M. Schuiling, W. Timens and H. Maarsingh are gratefully acknowledged for their invaluable assistance.

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Authors and Affiliations

  1. Department of Molecular Pharmacology, University Centre for Pharmacy, Antonius Deusinglaan 1, 9713, AV Groningen, The Netherlands

    Herman Meurs, Ruud E Santing, René Remie, Fiona J Westerhof, Annet B Zuidhof, I Sophie T Bos & Johan Zaagsma

  2. Department of Pulmonology, University Medical Centre Groningen, Hanzeplein 1, 9713, GZ Groningen, The Netherlands

    Thomas W van der Mark

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Correspondence to Herman Meurs.

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Meurs, H., Santing, R., Remie, R. et al. A guinea pig model of acute and chronic asthma using permanently instrumented and unrestrained animals. Nat Protoc 1, 840–847 (2006). https://doi.org/10.1038/nprot.2006.144

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