Carotid chemoreflex activity restrains post‐exercise cardiac autonomic control in healthy humans and in patients with pulmonary arterial hypertension

Abstract

Key pointsr Dysfunction of post-exercise cardiac autonomic control is associated with increased mortality risk in healthy adults and in patients with cardiorespiratory diseases.r The afferent mechanisms that regulate the post-exercise cardiac autonomic control remain unclear.r We found that afferent signals from carotid chemoreceptors restrain the post-exercise cardiac autonomic control in healthy adults and patients with pulmonary arterial hypertension (PAH).r Patients with PAH had higher carotid chemoreflex sensitivity, and the magnitude of carotid chemoreceptor restraint of autonomic control was greater in patients with PAH as compared to healthy adults.r The results demonstrate that the carotid chemoreceptors contribute to the regulation of post-exercise cardiac autonomic control, and suggest that the carotid chemoreceptors may be a potential target to treat post-exercise cardiac autonomic dysfunction in patients with PAH.Abstract Dysfunction of post-exercise cardiac autonomic control predicts mortality, but its underlying mechanisms remain unclear. We tested whether carotid chemoreflex activity restrains post-exercise cardiac autonomic control in healthy adults (HA), and whether such restraint is greater in patients with pulmonary arterial hypertension (PAH) who may have both altered carotid chemoreflex and altered post-exercise cardiac autonomic control. Twenty non-hypoxaemic patients with PAH and 13 age-and sex-matched HA pedalled until 90% of peak work rate observed in a symptom-limited ramp-incremental exercise test. Recovery consisted of unloaded pedalling for 5 min followed by seated rest for 6 min. During recovery, subjects randomly inhaled either 100% O 2 (hyperoxia) to inhibit the carotid chemoreceptor activity, or 21% O 2 (normoxia) as control. Post-exercise cardiac autonomic control was examined via heart rate (HR) recovery (HRR; HR change after 30, 60, 120 and 300 s of recovery, using linear and non-linear regressions of HR decay) and HR variability (HRV; time and spectral domain analyses). As expected, the PAH group had higher carotid chemosensitivity and worse post-exercise HRR and HRV than HA. Hyperoxia increased HRR at 30, 60 and 120 s and absolute spectral power HRV in both groups.Additionally, hyperoxia resulted in an accelerated linear HR decay and increased time domain HRV during active recovery only in the PAH group. In conclusion, the carotid chemoreceptors restrained recovery of cardiac autonomic control from exercise in HA and in patients with PAH, with the restraint greater for some autonomic indexes in patients with PAH.

Carotid chemoreflex and muscle metaboreflex interact to the regulation of ventilation in patients with heart failure with reduced ejection fraction

“…Another study, conducted in healthy humans, showed that the response to transient hypoxia at rest did not vary from pre‐ to post‐heavy‐intensity exercise (Clement et al, ), indicating therefore that the carotid chemoreflex sensitivity was unchanged. Together, data from our and previous studies (Clement et al, ; Paula‐Ribeiro et al, ) support that carotid chemoreceptors, per se, do not seem to contribute at all or contribute to a small part of the recovery from exercise.…”

“…A study in patients with right‐sided heart failure induced by pulmonary arterial hypertension employed a similar methodological approach to ours (Paula‐Ribeiro et al, ). One hundred percent O 2 was given in the inspired air 10 s before the onset of active recovery from incremental exercise.…”

“…Thereby, the contribution of the carotid chemoreflex to cardiorespiratory regulation seems to enhance during exercise (Niewiński et al, ; Stickland, Miller, Smith, & Dempsey, ). In contrast, however, the carotid chemoreflex does not seem to contribute to and respiratory pattern regulation during recovery from exercise in humans (Clement et al, ; Paula‐Ribeiro et al, ). Thus, an interaction among the carotid chemoreflex and other reflexes that operate during exercise, but not during recovery, possibly exist (Edgell & Stickland, ; Gujic et al, ; Scott et al, ).…”

Human Adaptations to Multiday Saturation on NASA NEEMO

“…The increased vagal modulation in acute saturated environments has been attributed to both elevated O 2 and increased pressure (independent of O 2 ) ( Lund et al, 1999 ). Mechanisms for this vagal responsiveness have been ascribed to vagal outflow compensating for O 2 and/or pressure induced vasoconstriction (baroreflex), increased cardiac efficiency due to elevated PPO 2 exposure in cardiac tissue, prolonged Q-T interval, and/or carotid chemoreflex inhibition ( Demchenko et al, 2013 ; Paula-Ribeiro et al, 2019 ; Goyal et al, 2020 ).…”

Continuous reduction in cerebral oxygenation during endurance exercise in patients with pulmonary arterial hypertension

“…As such, brain hypoxia sensors can modulate the neurovascular coupling to regional cerebral deoxygenation via astrocytes and pericytes, which in turn stimulate the brain stem neuronal respiratory network resulting in hyperventilation. Secondly, both peripheral and central chemoreceptors overactivity in PAH (Malenfant et al, 2017; Paula‐Ribeiro et al, 2019; Vicenzi et al, 2016) might stimulate ventilation in an additive manner. Smith et al demonstrated an hyperadditive two to fourfold response change in the central chemoreceptor response to carotid chemoreceptors hypersensitivity, resulting in further increase in ventilation in awaked dogs (Smith, Blain, Henderson, & Dempsey, 2015).…”