Peripheral Chemoreflex Regulates Post‐exercise Cardiac Vagal Reactivation in Healthy Humans and Patients with Pulmonary Arterial Hypertension
Authors: Paula‐Ribeiro Marcelle , Ribeiro Indyanara C. , Aranda Liliane , Silva Talita M , Costa Camila M , Ramos Roberta P , Arakaki Jaquelina O , Cravo Sergio L , Nery Luiz E , Stickland Michael K , Silva Bruno M 
Published: November 2023

The fast post‐exercise heart rate recovery (HRR) is valid, reproducible, and widely used in clinical practice to assess the cardiac vagal function. However, the mechanisms that regulate it remain unclear. As the peripheral chemoreflex regulates resting cardiac activity, and this reflex is sensitized by physical exercise, we hypothesized that the peripheral chemoreflex could regulate the post‐exercise cardiac vagal reactivation in healthy humans. Additionally, we hypothesized that the peripheral chemoreflex could contribute to the reduction of post‐exercise cardiac vagal reactivation in a clinical population that has been associated with high peripheral chemosensitivity. To test the first hypothesis, seven young men underwent ramp exercise tests then, during recovery, randomly inhaled either 1) 12% of O2 to stimulate the peripheral chemoreflex (i.e., hypoxia), 2) 100% of O2 to inhibit the peripheral chemoreflex (i.e., hyperoxia), or 3) 21% of O2 as control (i.e., normoxia). To test the second hypothesis, 14 adults with pulmonary arterial hypertension (PAH) underwent the same protocol, but randomly inhaled 100% or 21% of O2 during recovery. Of note, all the subjects were blinded about the inspired O2 concentration, which was changed slightly before the onset of recovery, not to disturb physiological responses during ramp exercise. ECG was registered and cardiac vagal reactivation was assessed via: 1) HRR, calculated as the difference between peak HR (HRpeak) and HR after 30 s (HRR30s) and 1 min (HRR1min) of recovery, and 2) HR variability (HRV), calculated as the root mean square of successive R‐R intervals difference (RMSSD) of 30‐s data segments throughout 5‐min of recovery. The chemoreflex sensitivity was assessed by the ventilatory response to transient nitrogen inhalation at rest. Healthy subjects showed similar HRpeak among conditions (hypoxia: 156 ± 10 vs. hyperoxia: 153 ± 7 vs. normoxia: 156 ± 9 beats/min, mean ± SD, P = 0.60). Their HRR30s was lower in hypoxia (5 ± 5 beats/min) than hyperoxia (22 ± 6 beats/min, P <0.01) and normoxia (17 ± 8 beats/min, P <0.01). HRR1min and RMSSD throughout the recovery period were lower in hypoxia than hyperoxia (HRR1min: 19 ± 10 vs. 35 ± 6 beats/min, P = 0.03; RMSSD: 3.5 ± 1.1 vs. 5.4 ± 1.3 ms, P = 0.04). Patients with PAH showed higher chemosensitivity than young healthy men. Their HRpeak was similar between conditions (hyperoxia: 147 ± 17 vs. normoxia: 148 ± 18 beats/min, P = 0.78). HRR30s (10 ± 5 vs. 5 ± 4 beats/min, P <0.001) and HRR1min (19 ± 9 vs. 15 ± 8 beats/min, P = 0.01) were higher in hyperoxia than normoxia. RMSSD was similar between conditions (P = 0.60). Therefore, collectively, these results indicate that the peripheral chemoreflex regulates the post‐exercise cardiac vagal reactivation in healthy humans, and, also, mediates reduction of cardiac vagal reactivation in patients with PAH.

Support or Funding Information

The study was supported by São Paulo Research Foundation, FAPESP (2014/24294‐6; 2015/22198‐2)