Chronic hypoxic hypercapnia modifies in vivo and in vitro ventilatory chemoreflexes in the cane toad

Previous studies have shown that exposure to chronic hypoxia (CH) and chronic hypercapnia (CHC) alone have opposite effects on central respiratory-related pH/CO(2) chemosensitivity in the cane toad (Bufo marinus). This study examined the effects of chronic hypoxic hypercapnia (CHH) on central pH/CO(2) chemosensitivity. Cane toads were maintained at 10% O(2) and 3.5% CO(2) for 10 days. Changes in central pH/CO(2)-sensitive fictive breathing were measured using in vitro brainstem-spinal cord preparations. Whole animal experiments examined the effects of CHH on in vivo ventilatory responses. In vitro, CHH augmented fictive breathing frequency but attenuated the integrated fictive breath area such that total fictive breathing was not altered. The effects on frequency were mediated by changes in the number of episodes/min rather than breaths/episode. In vivo, CHH blunted the ventilatory response to severe hypoxia and moderate hypercapnia. The results indicate that CHH alters breathing pattern in response to central chemoreceptor stimulation in vitro and modifies in vivo ventilatory chemoreflexes.