The essential role of peripheral respiratory chemoreceptor inputs in maintaining breathing revealed when CO2 stimulation of central chemoreceptors is diminished.
Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep. Studies in sleeping dogs suggest that withdrawal of peripheral chemoreceptor (carotid body) activation following transient ventilatory overshoots plays an essential role in causing apnoea, raising the possibility that sustaining carotid body activity during ventilatory overshoots may prevent apnoea. To test whether sustained peripheral chemoreceptor activation is sufficient to drive breathing, even in the absence of central chemoreceptor stimulation and vagal feedback, we used a vagotomized, decerebrate dual-perfused in situ rat preparation in which the central and peripheral chemoreceptors are independently and artificially perfused with gas-equilibrated medium. At varying levels of carotid body stimulation (CB PO2/PCO2: 40/60, 100/40, 200/15, 500/15 Torr), we decreased the brainstem perfusate PCO2 in 5 Torr steps while recording phrenic nerve activity to determine the central apnoeic thresholds. The central apnoeic thresholds decreased with increased carotid body stimulation. When the carotid bodies were strongly stimulated (CB 40/60), the apnoeic threshold was 3.6 ± 1.4 Torr PCO2 (mean ± SEM, n = 7). Stimulating carotid body afferent activity with either hypercapnia (60 Torr PCO2) or the neuropeptide pituitary adenylate cyclase-activating peptide restored phrenic activity during central apnoea. We conclude that peripheral stimulation shifts the central apnoeic threshold to very hypocapnic levels that would likely increase the CO2 reserve and have a protective effect on breathing. These data demonstrate that peripheral respiratory chemoreceptors are sufficient to stave off central apnoeas when the brainstem is perfused with low to no CO2.
Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
Marie-Noëlle
MN
Fiamma
Edward T
ET
O'Connor
Arijit
A
Roy
Ines
I
Zuna
Richard J A
RJ
Wilson
D000818:Animals; D001049:Apnea / Q000503:physiopathology; D001933:Brain Stem / Q000098:blood supply / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood*; D002344:Carotid Body / Q000187:drug effects / Q000502:physiology*; D003655:Decerebrate State; D004558:Electric Stimulation; D008297:Male; D010791:Phrenic Nerve / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D013268:Stimulation, Chemical; D014628:Vagotomy; D014630:Vagus Nerve / Q000601:surgery
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D002245:Carbon Dioxide