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Invasive lung function measurement in common marmosets (Callithrix jacchus)

: Wichmann, Judy; Curths, Christoph; Dunker, Sarah; Windt, Horst; Hoymann, Heinz Gerd; Lauenstein, Hans Dieter; Becker, Tamara; Kaup, Franz-Josef; Braun, Armin; Knauf, Sascha

American Journal of Respiratory and Critical Care Medicine 187 (2013), Art. A4066
ISSN: 1073-449X
ISSN: 0003-0805
ISSN: 1535-4970
American Thoracic Society (ATS International Conference) <2013, Philadelphia/Pa.>
Journal Article, Conference Paper
Fraunhofer ITEM ()

In rodents, lung function measurement is a standard technique used e.g. in asthma models for testing drug safety and efficacy. Fraunhofer ITEM uses common marmosets (Callitrix jacchus), small New World non-human primates, to establish translational models for human obstructive airway diseases. While an LPS-induced lung inflammation model has been published, a model for allergic asthma in house dust mite allergen sensitized marmosets is currently under investigation. Especially in the latter, lung function measurement serves as an important readout parameter. This study established a data base of lung function parameters and methacholine induced bronchoconstriction.
Twelve healthy marmosets were used to obtain physiological baseline data. A custom-made invasive lung function measurement device for marmosets has been build up by Fraunhofer ITEM. The device is able to aerosolize and deposit defined doses of pharmacological or provocative substances during measurement. Under general anesthesia, marmosets were intubated and connected to the device. A pulse oximeter was used to monitor heart rate and blood oxygen saturation. Lung function parameters such as lung resistance (RL), esophageal pressure (Poes), dynamic compliance (Cdyn), mid-expiratory flow (EF50), breath frequency, tidal (Vt) and minute volume (MV), time of brake and time of pause were recorded by Notocord-hem software (NOTOCORD, Croissy Sur Seine, France). After baseline measurement, each animal received methacholine (A2251, Sigma Aldrich, Steinheim), a non-selective muscarinic receptor agonist, in increasing dosages (0.5-1-2-4 and 8 microgram) via inhalation. Methacholine provocation was stopped when RL exceeded 150 % of individual baseline. Then, animals were treated with a puff of salbutamol (Salbutamol-ratiopharm-N) and a final record demonstrated bronchodilatation.
Healthy marmosets possessed a high competence to regulate breath in adaption to the methacholine provocation. As expected, all marmosets showed a remarkable increase of RL due to an increase of Poes and a decrease of EF50 in relation to the applied methacholine doses. Delta RL rose from 79±18% at a methacholine concentration of 0.5 microgram, to 139±35% and 213±61% until 302±126% (mean±SEM, n=5-12) at a final provocative methacholine dose of 8 microgram Cdyn reacted contrary wise. Due to a down regulation of Vt, breath frequency rose continuously from a baseline mean of 26±2 min-1 up to 38±7 min-1 (mean±SEM, n=7-12) at a methacholine concentration of 4 microgram, while MV was compensated with no remarkable changes.
In conclusion, Fraunhofer ITEM developed the first custom-made lung function measurement device for commonmarmosets. Lung function parameters from healthy marmosets were generated to provide baseline data.