Effect of coj on entrainment of the respiratory rhythm to a mechanical ventilator in sleeping humans

Changes in respiratory drive by CO, manipulation can change the phase resetting response of the respiratory oscillator of anesthetized cats to a single discrete stimulus. We hypothesized that the ease with which the oscillator of sleeping humans can be entrained to periodic machine breaths varied inversely with respiratory drive. To test this, we examined the range of machine rates over which inspiratory activity can be 1:1 entrained to a mechanical ventilator (MV) in normal volunteers during NREM sleep under isocapnic (n=8), hypocapnic (n=5), and hypercapnic (n=3) conditions. Room air or inspired CO₂ was delivered through a nasal mask and PETCQI kept equal to 3 torr below or 3 torr above eupneic P_ETCO2. Flow was constant at 25 or 35 L/min and tidal volume (V_T) was set to 1.3-1.5 of that measured during unassisted breathing. Trigger rate (f_T) was measured in the assist/control mode with machine rate (f_M) set to 2 breaths/min (bpm). Machine trigger mechanisms were then disabled and f_M was decreased or increased 1 bpm every 3 min relative to f _T. Inspiratory effort rate (J_s) was measured from diaphragm and parastemal EMG recordings. Reduction in drive during hypocapnia was evident by loss of detectable inspiratory activity. An increased drive during hypercapnia was shown by 2-3 fold increases in inspiratory efforts. A 1:1 entrainment pattern was observed until f_M was decreased to 2 bpm (±1) below f _T. This was true despite varying PEJCCH. on average, 3 torr above or below eupneic P_ETCO2. We conclude that differences in drive do not affect the ease with which the oscillator can be entrained to MV. It is possible that this observed lack of effect is related to differences in species, is related to differences in the mechanisms underlying phase resetting in response to single vs multiple perturbations, or. that the magnitude of change in drive in our study was smaller. NIH MO1-RR00585 and a Mayo Foundation grant.