Source of respiratory drive during periodic breathing in lambs

In order to investigate the mechanisms underlying periodic breathing (PB), we studied the initiation of breathing after passive hyperventilation in 14 anaesthetised 10-20 day old lambs. Eight of the lambs exhibited PB following post-hyperventilation apnea (PHA), with an epoch duration of 82.4 +/- 14.2 sec (mean +/- SEM), a cycle duration of 9.7 +/- 0.7 sec and a ratio of ventilatory duration to apnea duration (V-A ratio) of 1.24 +/- 0.32. The remaining lambs showed stable breathing patterns following PHA. The ventilatory response to isocapnic hypoxia was significantly greater in the group that had PB (-7.2 +/- 1.0 ml min-1% Sao2-1 kg-1) than in the animals that did not (-2.5 +/- 1.0 ml min-1%Sao2-1 kg-1). Using experimentally determined ventilatory response curves to O2 and CO2 we calculated that the swings in Sao2 and Paco2 during PB generated chemical drive that accounted for only 16.2% of the ventilatory oscillations observed during PB. Much of the remaining drive appeared to originate in the 'switch-on' characteristics of the respiratory controller, in lambs that exhibited periodic breathing, when breathing began after PHA ventilation jumped abruptly from zero to 55.1% of the eupneic ventilation. The magnitude of this jump in ventilation accounted for 51.9% of the amplitude of ventilatory oscillations that occur during PB. We speculate that this previously unrecognised feature of the respiratory controller, together with an elevated sensitivity to hypoxaemia, play crucial roles in generating PB in the infant.