A comparison of the ventilatory response of sleeping newborn lambs to step and progressive hypoxaemia

1. Slight variations in the rate at which hypoxaemia develops may significantly alter the ventilatory response (VR) elicited. Here we have developed a technique to compare the VRs elicited from sleeping newborn lambs by specific (step versus progressive), short-duration (< or = 5 min) episodes of hypoxaemia. The results may help us understand the limitations of using tests which deliver poorly defined stimuli to evaluate the postnatal development of the oxygen chemoreflex. 2. The VRs of five lambs elicited by a 5 min step or progressive reduction in the arterial oxygen saturation (Sa,O2) during quiet sleep were compared. Minute ventilation (V1, face mask) and Sa,O2 (pulse oximeter) were measured continuously. Alternate step (Sa,O2 reduced to 80-85% within 60 s and maintained for a further 4 min) and progressive tests (progressive reduction in Sa,O2 to 80% over 5 min) were administered daily between postnatal days 2-14. 3. There was a significant difference between the mean VR to step versus progressive hypoxaemia. The VR to a step challenge was biphasic (delta Vi = +32 +/- 5% at 1 min and -1 +/- 4% at 5 min; mean +/- S.E.M.). Progressive hypoxaemia elicited a more subdued but sustained hyperpnoea (delta Vi = +11 +/- 2% at 1 min and +11 +/- 4% at 5 min). The difference between these two response profiles was statistically significant (P < 0.001). 4. Mean responses of lambs aged < or = 5 days (4 +/- 0.2 days) and > or = 9 days (10 +/- 0.3 days) were also compared. There was an upward shift in the position of step and progressive response curves of older lambs, reflecting primarily the increased vigour of the initial hyperpnoea elicited by step (delta Vi at 1 min = +20 +/- 4% at 4 days vs. +40 +/- 11% at 10 days) as well as progressive (delta Vi at 1 min = +6 +/- 2% at 4 days vs. +17 +/- 5% at 10 days) hypoxaemia. 5. Qualitatively different VRs may be elicited from the newborn, depending upon the specific hypoxaemic profile administered. Therefore, to evaluate the significance of VRs elicited in response to classical, steady-state hypoxia at different postnatal ages properly, the stimulus must be accurately described.