Increased propensity for apnea via dopamine-induced carotid body inhibition in sleeping dogs

Abstract

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 Pco2 (PetCO2) between eupnea and the apneic threshold, the “CO2 reserve,” by gradually reducing PetCO2 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 CO2 retention of 3.9 ± 1.9 mmHg and a brief period of ventilatory instability. The apneic threshold PetCO2 rose 5.1 ± 1.9 Torr; thus the CO2 reserve was narrowed from −3.9 ± 0.62 Torr in control to −2.7 ± 0.78 Torr with dopamine. This decrease in the CO2 reserve with dopamine resulted solely from the 20.5 ± 11.3% increase in plant gain; the slope of the ventilatory response to CO2 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 CO2 reserve below eupnea. This narrowing is due solely to an increase in plant gain as the slope of the ventilatory response to CO2 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.