CO2relaxes parenchyma in the liquid-filled rat lung

CO2regulation of lung compliance is currently explained by pH- and CO2-dependent changes in alveolar surface forces and bronchomotor tone. We hypothesized that in addition to, but independently of, those mechanisms, the parenchyma tissue responds to hypercapnia and hypocapnia by relaxing and contracting, respectively, thereby improving local matching of ventilation (V̇a) to perfusion (Q̇). Twenty adult rats were slowly ventilated with modified Krebs solution (rate = 3 min−1, 37°C, open chest) to produce unperfused living lung preparations free of intra-airway surface forces. The solution was gassed with 21% O2, balance N2, and CO2varied to produce alveolar hypocapnia (Pco2= 26.1 ± 2.4 mmHg, pH = 7.56 ± 0.04) or hypercapnia (Pco2= 55.0 ± 2.3 mmHg, pH = 7.23 ± 0.02). The results show that lung recoil, as indicated from airway pressure measured during a breathhold following a large volume inspiration, is reduced ∼30% when exposed to hypercapnia vs. hypocapnia ( P < 0.0001, paired t-test), but stress relaxation and flow-dependent airway resistance were unaltered. Increasing CO2from hypo- to hypercapnic levels caused a substantial, significant decrease in the quasi-static pressure-volume relationship, as measured after inspiration and expiration of several tidal volumes, but hysteresis was unaltered. Furthermore, addition of the glycolytic inhibitor NaF abolished CO2effects on lung recoil. The results suggest that lung parenchyma tissue relaxation, arising from active elements in response to increasing alveolar CO2, is independent of (and apparently in parallel with) passive tissue elements and may actively contribute to V̇a/Q̇ matching.