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11 Medical and Health Sciences, Respiratory System, 3201 Cardiovascular medicine and haematology

Abstract:

One of the important clinical features of asthma is the exercise intolerance due to an exacerbation. Yet, to our knowledge, this endpoint has never been assessed in animal models of asthma. On day 1 and 8, BALB/C mice received 0.3% toluene diisocyanate (TDI; 20 µl/ear) or vehicle (AOO, acetone/olive oil) on each ear. On day 15, they received a single intranasal instillation of 0.1% TDI (10 µl/nostril) or AOO. Ventilatory function was monitored by whole body plethysmography (Penh) immediately after instillation. One and 22 h hour after instillation the mice were made to swim, against a limited downward current, until exhaustion. On day 16, i.e. 24 h after intranasal instillation, methacholine reactivity (AHR) was assessed by whole body plethysmography. Pulmonary inflammation was assessed by bronchoalveolar lavage (BAL. TDI-sensitized and intranasally instilled mice showed an immediate increase in Penh after intranasal challenge, a late increase in methacholine reactivity (24 h) and a reduced swim capacity by 13 min and 5 min, 1 h and 22 h after intranasal instillation, respectively, compared with the control groups (1st swim test: 22 min and 2nd swim test: 19 min). BAL neutrophils were significantly increased in the TDI-treated group (20 % - 51 %) compared to the vehicle treated mice (4 % - 12 %). There were clear correlations (nonparametric Spearman) between the first swim test and the early increase in Penh (r = -0.84, p<0.001) and the late increase in AHR (r = -0.72, p<0.01). The second swim test correlated also with the early increase in Penh (r = -0.85, p<0.001) and the increased AHR (r = -0.83, p<0.001). This is the first study to use an exercise test to measure the physiologic response in a mouse model of asthma. It is likely that this reduced exercise capacity reflects the occurrence of hypoxemia.