Submitted on May 20, 2004
Accepted on October 6, 2004
The Impact of Changes in Inspired Oxygen and Carbon Dioxide on Respiratory Instability in the Lamb
Malcolm H. Wilkinson1*, Kah-Ling Sia1, Elizabeth M. Skuza1, Vojta Brodecky1, and Philip J. Berger1
1 Ritchie Centre for Baby Health Research, Institute of Reproduction and Development, Monash University, Clayton, Victoria, Australia
* To whom correspondence should be addressed. E-mail: mal.wilkinson{at}med.monash.edu.au.
We examined the effect of hypoxia and hypercapnia administered during deliberately induced periodic breathing (PB) in 7 lambs following post-hyperventilation 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 > 1, replacement of the inspired gas with one of reduced PO2 lowers LG; if we made PIO2 approximate alveolar PO2, we predict LG would be approximately zero, and breathing would promptly stabilize. In 6 lambs we switched the inspired gas from
FIO2 = 0.4 to FIO2 = 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 6 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 lamb and adult human demonstrate that PB has differing underlying mechanisms in the two species.
