Blunted ventilatory response to hypoxia/hypercapnia in mice with cigarette smoke-induced emphysema

It has been reported that the degree of emphysema induced by chronic cigarette smoke (CS) is greater in female C3H/HeN mice as compared to other mouse strains. We hypothesized that these mice would develop the similar major characteristics seen in hypercapnic patients with chronic obstructive pulmonary disease (COPD), including emphysema, pulmonary inflammation, hypercapnia/hypoxemia, rapid breathing, and attenuated ventilatory response (AVR). Mice were exposed either to CS or filtered air (FA) for 16 weeks. After exposure, arterial blood gases and minute ventilation were measured before and during chemical challenges in anesthetized and spontaneously breathing mice. We found that as compared to FA, CS exposure caused emphysema and pulmonary inflammation associated with: (1) hypercapnia and hypoxemia, (2) rapid breathing, and (3) AVR to 25 breaths of pure N(2), 5% CO(2) alone, and 5% CO(2) coupled with 10% O(2). The similarity of these pathophysiological characteristics between our mouse model and COPD patients suggests that this model could be effectively applied to study COPD pathophysiology, especially central mechanisms of the AVR genesis.