title: Increased peripheral chemosensitivity via dopaminergic manipulation promotes respiratory instability in lambs.
abstract: Periodic breathing (PB) is an instability of the respiratory control system believed to be mediated principally by the peripheral chemoreceptors. We hypothesised that domperidone, a dopamine D(2)-receptor antagonist that increases carotid body sensitivity to O(2) and CO(2), would promote PB through an increase in the loop gain (LG) of the respiratory control system. Domperidone significantly increased controller gain for oxygen (p<0.05) and gave rise, following post-hyperventilation apnea, to an increased incidence of PB (14% vs. 86%), an increased PB epoch duration, and a decrease in duty ratio of PB (p<0.001); these changes are consistent with domperidone increasing LG. Although domperidone increased controller gain for CO(2) (p<0.05), the contribution of Pa(CO)(2) oscillations to the genesis of PB in the lamb remained small. We conclude that domperidone increases LG in the lamb via an increase in controller gain for oxygen. Our study demonstrates that a quantitative understanding of the factors that determine LG provides insight into the cause of PB.
authors.affiliation: Ritchie Centre for Baby Health Research, Monash Institute of Medical Research, Monash University, Monash Medical Centre, Level 5, 246 Clayton Road, Clayton 3168, Australia.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Edwards
authors.forename: Scott A
authors.initials: SA
authors.lastname: Sands
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Skuza
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Stockx
authors.forename: Vojta
authors.initials: V
authors.lastname: Brodecky
authors.forename: Malcolm H
authors.initials: MH
authors.lastname: Wilkinson
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Berger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001049:Apnea / Q000503:physiopathology; D002245:Carbon Dioxide / Q000494:pharmacology; D002344:Carotid Body / Q000166:cytology*; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D010100:Oxygen / Q000494:pharmacology; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D012756:Sheep
chemical_list: D018492:Dopamine Antagonists; D002245:Carbon Dioxide; D004294:Domperidone; D010100:Oxygen; D004298:Dopamine