Functional Role of Carbon Dioxide on Intermittent Hypoxia Induced Respiratory Response following Mid‐cervical Contusion in the Rat

Abstract

Intermittent hypoxia can induce ventilatory long-term facilitation, thereby contributing to respiratory motor recovery following spinal cord injury. However, it is unclear whether combination of hypoxia and hypercapnia and strengthen the efficacy of intermittent respiratory stimuli on the respiratory function. Accordingly, the purpose of this study is to evaluate the functional role of intermittent or sustained hypercapnia on intermittent hypoxia-induced respiratory recovery following mid-cervical contusion in the rat. The breathing pattern of unanesthetized rats at the subchronic and chronic injured stages was measured in response to one of the following treatments: (1) Intermittent hypercapnic-hypoxia (10x5 min 10%O2+4%CO2 with 5 min normoxia interval); (2) Intermittent hypoxia with sustained hypercapnia (10x5 min 10%O2+4%CO2 with 5 min 21%O2+4%CO2 interval); (3) Intermittent hypoxia (10x5 min 10%O2 with 5 min normoxia interval); (4) Intermittent hypercapnia (10x5 min 21%O2+4%CO2 with 5 min normoxia interval); (5) Sustained hypercapnia (100 min, 21% O2+4% CO2); (6) Sustained normoxia (100 min, 21% O2). The results demonstrated that the tidal volume was significantly enhanced to a similar magnitude following intermittent hypercapnic-hypoxia, intermittent hypoxia with sustained hypercapnia, and intermittent hypoxia in subchronically injured animals. Nevertheless, only intermittent hypercapnic-hypoxia and intermittent hypoxia were able to evoke long-term facilitation of the tidal volume at the chronic injured stage. Notably, the magnitude of tidal volume recovery is independent on the lesion severity or baseline tidal volume at both subchronic and chronic injured stages. These results suggest that mild intermittent or sustained hypercapnia did not further enhance the therapeutic efficacy of intermittent hypoxia-induced respiratory recovery in mid-cervical contused animals. Future studies are warranted to evaluate whether intermittent hypercapnia or sustained hypercapnia can modulate the respiratory function following daily intermittent hypoxia training.