Chemosensory ventilatory responses in the mutant mice with Presbyterian hemoglobinopathy.

The working hypothesis of this study was that chronically increased tissue oxygenation would facilitate respiratory endurance to chemical stimuli. We investigated the ventilatory responses to hypoxia and hypercapnia before and after carotid chemodenervation in the anesthetized, spontaneously breathing Presbyterian, which carry a low affinity variant of hemoglobin, and in wild-type mice. We found a dampening of all chemosensory responses in Presbyterian hemoglobinopathy. Particularly, the Presbyterian mouse with intact carotid body innervation was more vulnerable to hypoxia than the wild-type mouse, showing an accelerated decline in breathing frequency which was not counterbalanced by tidal respiration. We further found that chemodenervation in the Presbyterian mouse, performed in normoxia, led to respiratory arrest. The study shows enhanced susceptibility of respiration to hypoxia and indispensability of neural input from the carotid body for upholding the central respiratory controller's function in Presbyterian hemoglobinopathy. The study also suggests a relationship between hemoglobin-oxygen dissociation and respiration, which points to a metabolic, tissue oxygenation-linked component of respiratory regulation.