Increased propensity for apnea via dopamine-induced carotid body inhibition in sleeping dogs.
We determined the effects of specific carotid body chemoreceptor inhibition on the propensity for apnea during sleep. We reduced the responsiveness of the carotid body chemoreceptors using intravenous dopamine infusions during non-rapid eye movement sleep in six dogs. Then we quantified the difference in end-tidal Pco(2) (Pet(CO(2))) between eupnea and the apneic threshold, the "CO(2) reserve," by gradually reducing Pet(CO(2)) transiently with pressure support ventilation at progressively increased tidal volume until apnea occurred. Dopamine infusions decreased steady-state eupneic ventilation by 15 +/- 6%, causing a mean CO(2) retention of 3.9 +/- 1.9 mmHg and a brief period of ventilatory instability. The apneic threshold Pet(CO(2)) rose 5.1 +/- 1.9 Torr; thus the CO(2) reserve was narrowed from -3.9 +/- 0.62 Torr in control to -2.7 +/- 0.78 Torr with dopamine. This decrease in the CO(2) reserve with dopamine resulted solely from the 20.5 +/- 11.3% increase in plant gain; the slope of the ventilatory response to CO(2) below eupnea was unchanged from normal. We conclude that specific carotid chemoreceptor inhibition with dopamine increases the propensity for apnea during sleep by narrowing the CO(2) reserve below eupnea. This narrowing is due solely to an increase in plant gain as the slope of the ventilatory response to CO(2) below eupnea was unchanged from normal control. These findings have implications for the role of chemoreceptor inhibition/stimulation in the genesis of apnea and breathing periodicity during sleep.
Chenuel
Bruno J
BJ
Laboratoire de Physiologie, Faculté de Médecine de Nancy, Ave. de la Forêt de Haye, B.P. 184, 54505 Vandoeuvre-lès-Nancy Cedex, France. bruno.chenuel@medecine.uhp-nancy.fr
Smith
Curtis A
CA
Henderson
Kathleen S
KS
Dempsey
Jerome A
JA
D000818:Animals; D002344:Carotid Body / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004298:Dopamine / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D007262:Infusions, Intravenous; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012891:Sleep Apnea Syndromes / Q000139:chemically induced* / Q000503:physiopathology
D004298:Dopamine