Heartbeats entrain breathing via baroreceptor-mediated modulation of expiratory activity

Author: William H Barnett1, David M Baekey2, Julian F R Paton3, Thomas E Dick4,5, Erica A Wehrwein6, Yaroslav I Molkov1,7
1 Department of Mathematics and Statistics, Georgia State University, Atlanta, GA.
2 Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL.
3 Manaaki Mānawa - The Centre for Heart Research, Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
4 Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH.
5 Department of Neurosciences, Case Western Reserve University, Cleveland, OH.
6 Department of Physiology, Michigan State University, East Lansing, MI.
7 Neuroscience Institute, Georgia State University, Atlanta, GA.
Conference/Journal: Exp Physiol
Date published: 2021 Mar 21
Other: Special Notes: doi: 10.1113/EP089365. , Word Count: 267

New findings:
Cardio-ventilatory coupling refers to the onset of inspiration occurring at a preferential latency following the last heartbeat in expiration. According to the cardiac-trigger hypothesis, the pulse pressure initiates an inspiration via baroreceptor activation. However, the central neural substrate mediating this coupling remains undefined. Using a combination of animal data, human data and mathematical modeling, this study tests the hypothesis that the heartbeat, by way of pulsatile baroreflex activation, controls the initiation of inspiration which occurs through a rapid neural activation loop from the carotid baroreceptors to Bötzinger Complex expiratory neurons.

Cardio-ventilatory coupling refers to a heartbeat (HB) occurring at a preferred latency prior to the next breath. We hypothesized that the pressure pulse generated by a HB activates baroreceptors that modulates brainstem expiratory neuronal activity and delays the initiation of inspiration. In supine male subjects, we recorded ventilation, electrocardiogram, and blood pressure during 20-min epochs of baseline, slow-deep breathing, and recovery. In in situ rodent preparations, we recorded brainstem activity in response to pulses of perfusion pressure. We applied a well-established respiratory network model to interpret these data. In humans, the latency between a HB and onset of inspiration was consistent across different breathing patterns. In in situ preparations, a transient pressure pulse during expiration activated a subpopulation of expiratory neurons normally active during post-inspiration; thus, delaying the next inspiration. In the model, baroreceptor input to post-inspiratory neurons accounted for the effect. These studies are consistent with baroreflex activation modulating respiration through a pauci-synaptic circuit from baroreceptors to onset of inspiration. This article is protected by copyright. All rights reserved.

PMID: 33749038 DOI: 10.1113/EP089365