Role of vagal C-fiber afferents in respiratory response to hypercapnia

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Abstract
The respiratory response to hypercapnia was investigated in 10 anesthetized rabbits by use of a rebreathing technique. The responses were obtained in 3 situations: with 1 intact vagus nerve (control), during differential block of conduction and after vagotomy. Differential block was achieved using anodal hyperpolarization by application of a direct current to the cervical vagus nerve. Great care was taken during the differential block to establish that all impulse conduction in myelinated fibers of the cervical vagus nervus was abolished but that the nonmyelinated fibers conducted normally. Additionally, in 5 more rabbits the nature of the differential block was confirmed from single-fiber recordings of activity in both myelinated and nonmyelinated fibers. The same increase in tidal volume in response to hypercapnia was present in all 3 experimental situations, indicating that it was not vagally mediated. The increase in frequency in response to hypercapnia in the control state was abolished by vagotomy but preserved when only the nonmyelinated fibers were functioning during the differential block. This increased frequency response, attributable to decreases in both inspiratory and expiratory durations, was usually enhanced during the differential block, despite the slower deeper pattern of breathing attributed to loss of activity in myelinated fibers. The implications of this reflex increase in frequency in response to hypercapnia, mediated by nonmyelinated vagal endings in the lung, are discussed.