Stimulation of breathing by activation of pulmonary peripheral afferents in rabbits

Respiratory response to selective activation of vagal afferents in the peripheral airways was investigated in anesthetized, open-chest, and artificially ventilated rabbits. Phrenic activity was used as an index of central respiratory drive before and after injection of hypertonic saline (8.1%, 0.1 ml) into the periphery of the lung to stimulate the afferents. The amplitude of "integrated" phrenic activity and phrenic burst rate increased by 19 +/- 3.4 and 53.7 +/- 12.7% (n = 23; P < 0.001), respectively. The response peaked at 5.5 +/- 1.6 s and returned to the baseline at 7 min (median) after the injection. The magnitude of the response was positively related to the concentration of injected NaCl. The response could not be elicited by injection of normal saline and was abolished by vagotomy. Because artificial ventilation caused phrenic activity to be entrained with the ventilator, respiratory drive was further assessed after the ventilator was stopped. Again, neural hyperpnea and tachypnea were observed. Because activation of a small fraction of the pulmonary peripheral afferents resulted in vigorous stimulation of respiratory drive, we speculate that initiation of this reflex may contribute to hyperpnea and tachypnea under both physiological and pathophysiological conditions.