Effects of pulmonary and intercostal denervation on the response of breathing frequency to varying inspiratory flow

Abstract

In mechanically ventilated awake and sleeping humans, it has been shown that increasing inspiratory flow rate (V'I) exerted a reflex excitatory effect on respiratory output. Mechanoreceptors located in intercostal muscles or within the lung have been suggested as possible pathways that may mediate the excitatory effect of V'I. To test this, five patients with bilateral lung transplantation (LTP) and eight quadriplegics with spinal cord transection at the level of C6-C7 (QP) were studied. Patients were connected to a volume cycle ventilator in the assist volume-control mode and V'I was randomly changed. V'I pattern was square and all breaths were patient-triggered. V'I values of 30, 60 and 90 L · min-1 were studied. Each level of V'I was sustained for 15 breaths. Airway pressures, end-tidal partial pressure of carbon dioxide (PCO2), airflows and volumes were measured breath by breath. Thirty seven trials in LTP and sixty in QP, where V'I was randomly changed between 30 and 90 L · min-1, were analysed. In both groups of patients, minute ventilation increased and total breath duration decreased significantly as V'I increased. These changes were complete in the first breath after V'I transition, without evidence of adaptation of the response. The magnitude of the response did not differ between the two groups of patients and was comparable to that observed previously in conscious normal subjects. We conclude that the excitatory effect of inspiratory flow rate on breathing frequency persists in patients who have pulmonary or intercostal denervation. These results do not favour receptors located within the lung (below the resection lines) or in the intercostal muscles to mediate the response of breathing frequency to flow rate.