How do the Carotid Chemoreceptors Modulate Ventilatory Control and Cardiovascular Regulation at Rest and During Exercise in COPD?

Abstract

RATIONALEWe have recently demonstrated elevated activity and sensitivity of the carotid chemoreceptor (CC) in COPD, which may alter ventilatory and cardiovascular regulation at rest and during exercise. Accordingly, we sought to examine whether CC inhibition modifies ventilation and cardiovascular regulation at rest and during exercise in COPD.METHODSIn a randomized double blind crossover study, thirteen COPD patients (FEV1 predicted ± SD: 82 ± 19%) and thirteen healthy controls completed resting cardiovascular function measurements while receiving either intravenous (I.V.) saline or I.V. dopamine (2 mg/kg/min) while inspiring either room air or 100% O2 (order randomized). Participants then completed two time to symptom limitation constant load exercise tests at 75% peak power output, on separate days, while receiving either I.V. saline or dopamine (order randomized). At rest, arterial stiffness was determined by pulse‐wave velocity (PWV) and muscle sympathetic nerve activity (MSNA) was measured by microneurography. Ventilatory responses were evaluated using expired gas data and cardiac output (impedance cardiography) was collected to calculate vascular conductance (cardiac output/mean arterial pressure (MAP)). Exertional dyspnea was evaluated using a modified Borg scale and inspiratory capacity maneuvers were performed to determine operating lung volumes.RESULTSAt rest, CC inhibition with dopamine decreased central and peripheral PWV, ventilation and MAP (p<0.05) while increasing vascular conductance in COPD. No change in CV function was observed with dopamine in controls. CC inhibition with hyperoxia decreased peripheral PWV and MSNA (p<0.05) in COPD, while no change was observed in controls. At a standardized exercise time (isotime) of 4 minutes and at symptom limitation, minute ventilation was not different between saline and dopamine conditions in COPD or controls. Operating lung volumes and exertional dyspnea were not different between conditions within either group. Vascular conductance was increased (p<0.05) during exercise with dopamine in COPD, secondary to reduced MAP, while no change was observed in controls. There was no change in time‐to‐exhaustion in either group with dopamine.CONCLUSIONResults from the current study suggest that the CC plays a role in cardiovascular regulation at rest and during exercise in COPD; however, exercise ventilation, dyspnea and exercise tolerance were unaffected by CC inhibition in COPD patients. Interventions aimed at chronically reducing CC activity may be beneficial to reduce cardiovascular risk in COPD.Support or Funding InformationLung Association of Alberta/NWTCanadian Institute of Health ResearchThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.