Impact of changes in inspired oxygen and carbon dioxide on respiratory instability in the lamb

Abstract

. Impact of changes in inspired oxygen and carbon dioxide on respiratory instability in the lamb. J Appl Physiol 98: 437-446, 2005. First published October 8, 2004 doi:10.1152/japplphysiol.00532.2004We examined the effect of hypoxia and hypercapnia administered during deliberately induced periodic breathing (PB) in seven lambs following posthyperventilation apnea. Based on our theoretical analysis, the sensitivity or loop gain (LG) of the respiratory control system of the lamb is directly proportional to the difference between alveolar PO2 and inspired PO2. This analysis indicates that during PB, when by necessity LG is Ͼ1, replacement of the inspired gas with one of reduced PO2 lowers LG; if we made inspired PO2 approximate alveolar PO2, we predict that LG would be approximately zero and breathing would promptly stabilize. In six lambs, we switched the inspired gas from an inspiratory oxygen fraction of 0.4 to one of 0.12 during an epoch of PB; PB was immediately suppressed, supporting the view that the peripheral chemoreceptors play a pivotal role in the genesis and control of unstable breathing in the lamb. In the six lambs in which we administered hypercapnic gas during PB, breathing instability was also suppressed, but only after a considerable time lag, indicating the CO2 effect is likely to have been mediated through the central chemoreceptors. When we simulated both interventions in a published model of the adult respiratory controller, PB was immediately suppressed by CO2 inhalation and exacerbated by inhalation of hypoxic gas. These fundamentally different responses in lambs and adult humans demonstrate that PB has differing underlying mechanisms in the two species.Cheyne-Stokes respiration; hypoxia; hypercapnia; sleep apnea syndromes; control of breathing; periodic breathing PERIODIC BREATHING (PB), or Cheyne-Stokes respiration, appears under a wide range of physiological and clinical conditions. It is particularly prevalent during sleep, occurring at sea level in apparently normal-term and preterm infants (22,43), at high altitude in normal adults (27), and after hypoxic exposure in experimental animals (11,21). It also occurs in patients with congestive heart failure (36), with idiopathic central sleep apnea (52), with bilateral brain stem lesions (40), and in periodic obstructive sleep apnea (41). A form of PB can also be found in hibernating animals (7,34).Although it is often assumed that the underlying mechanisms causing PB in infants and adults are similar, in each case involving instability of the chemical control system that regulates breathing, there are some marked differences in the pattern of PB and its responses to changes in inspired gas that remain largely unexplained. For example, in preterm infants, the waxing and waning pattern of PB that is characteristic of the adult is replaced by a more or less abrupt on-off pattern that shows little change in tidal volume during the breathing phase (42); this pattern resembles that seen in hibernating animals (34). Furthermore, although the re...

A pilot study of sleep, cognition, and respiration under 4 weeks of intermittent nocturnal hypoxia in adult humans

“…Central apneas following return to normoxia or hyperoxia have been described under a variety of relatively brief experimental conditions. 25,26–28 Hypoxia can increase the sleep CO 2 apneic threshold and hyperoxia can lower it. 29 A combination of hypocapnia and hyperoxia has previously been demonstrated to produce central apnea during NREM sleep.…”

Postnatal Development of Periodic Breathing Cycle Duration in Term and Preterm Infants

“…Second, the temporally matched fall in PCD with PNA in the preterm and term infants suggests that the respiratory control system undergoes an adaptation to air breathing starting soon after birth, and that this adaptation is completed by 4 mo postnatally, regardless of whether birth is preterm or term. Third, since a number of studies suggest a dominant role for the peripheral chemoreceptors in the genesis of respiratory instability (3,4,6,14,20,21), the fall in PCD with PNA specifically points to a shortening of the time delays in the peripheral chemoreflex loop as causative. Interestingly, recent evidence suggests that delays in the response to a hypercapnic stimulus are significantly reduced in human infants over the first weeks of life while the peripheral O 2 chemoreflex shows little change (9).…”

Periodic breathing and oxygen supplementation in Chilean miners at high altitude (4200m)

“…Sleep apneas occur during sleep in humans (Lahiri et al, 1983;Berssenbrugge et al, 1983;Wickramasinghe and Anholm, 1999;Küpper et al, 2008;Nussbaumer-Ochsner et al, 2012) and animals (Pappenheimer, 1977;Han et al, 2002;Wilkinson et al, 2005) exposed to hypoxia or high altitude. Apneas may appear as low as 2400 m, increase with increasing altitude (Waggener et al, 1984;Bloch et al, 2010;Nussbaumer-Ochsner et al, 2012) and decrease with acclimatization (Waggener et al, 1984;Goldenberg et al, 1992;Nussbaumer-Ochsner et al, 2012).…”