Functional role of carbon dioxide on intermittent hypoxia induced respiratory response following mid-cervical contusion in the rat

Abstract

Intermittent hypoxia induces respiratory neuroplasticity to enhance respiratory motor outputs and is a potential rehabilitative strategy to improve respiratory function following cervical spinal injury. The present study was designed to evaluate the functional role of intermittent and sustained carbon dioxide (CO2) on intermittent hypoxia-induced ventilatory responses in rats with mid-cervical spinal contusion. 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 (10 × 5 min 10%O2 + 4%CO2 with 5 min normoxia interval); (2) Intermittent hypoxia with sustained hypercapnia (10 × 5 min 10%O2 + 4%CO2 with 5 min 21%O2 + 4%CO2 interval); (3) Intermittent hypoxia (10 × 5 min 10%O2 with 5 min normoxia interval); (4) Intermittent hypercapnia (10 × 5 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 intermittent hypoxia associated with intermittent hypercapnia or sustained hypercapnia induced a greater ventilatory response than sustained hypercapnia during stimulus exposure. 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; however, only intermittent hypercapnic-hypoxia and intermittent hypoxia were able to evoke long-term facilitation of the tidal volume at the chronic injured stage. These results suggest that mild intermittent hypercapnia did not further enhance the therapeutic effectiveness of intermittent hypoxia-induced respiratory recovery in mid-cervical contused animals. However, sustained hypercapnia associated with intermittent hypoxia may blunt ventilatory responses following intermittent hypoxia at the chronic injured stage.