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C3H female mice exposed to chronic cigarette smoke (CS) resemble the basic characteristics of chronic obstructive pulmonary disease (COPD) with hypercapnia
Author(s) -
Xu Fadi,
Zhuang Jianguo,
Wang Rurong,
March Thomas H.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a376
Subject(s) - hypercapnia , copd , medicine , exacerbation , ventilation (architecture) , respiratory system , anesthesia , respiratory minute volume , pathogenesis , cardiology , mechanical engineering , engineering
Appearance of hypercapnia (P a co 2 > 45 mmHg) in patients with COPD, a sign of imminent death within 3 years, is associated with the depressed ventilatory response (DVR) to hypercapnia. The mortality often occurs during exacerbation of COPD at which this respiratory impairment is worsened, and thereby leads to respiratory failure. The mechanisms of DVR are unclear. C3H female mice are vulnerable to developing CS‐induced emphysema. This study tested the hypothesis that the CS‐exposed mice closely resembled the major characteristics of hypercapnic COPD, including hypercapnia, rapid breathing and DRV. C3H adult female mice were either exposed to CS (100 mg TPM/m 3 in the first wk and 250 mg in the following wks) or filtered air (FA) for 16 weeks. After exposure, arterial blood samples were taken and minute ventilation measured before and during 5 min of 5% CO 2 alone or coupled with 10% O 2 in the anesthetized and spontaneously breathing mice. We found that as compared to FA, CS exposure: 1) caused emphysema characterized by a 33% increase in the mean linear intercept, a measure of alveolar size; 2) significantly increased P a co 2 by 26%, and decreased P a o 2 and S a o 2 by 13% and 15%, respectively (P < 0.05); 3) elevated baseline respiratory frequency by 26% (P < 0.05); and 4) blunted ventilation responses to hypercapnia and hypoxic hypercapnia by 11% and 30% (P < 0.05), respectively. These data strongly suggest that these CS‐exposed mice are ideal for future mechanistic studies on the pathogenesis of DVR. (Supported by ALA CI‐016N and NIH 74183)