Tonic peripheral chemoreflex activation contributes to cardiac autonomic modulation at rest and impairs cardiac baroreflex sensitivity during orthostatic challenge in patients with pulmonary arterial hypertension

Abstract

Patients with pulmonary arterial hypertension (PAH) often experience orthostatic hypotension, and this may be mediated, to some extent, by impaired baroreflex sensitivity (BRS). The impairment in BRS is possibly caused by multiple factors. Of note, however, accumulating evidence has supported that tonic peripheral chemoreflex activation plays a key role for autonomic impairment in diseases like systemic hypertension and heart failure, due to, in part, alterations that are also commonly found in PAH (e.g., inflammation and oxidative stress). Thus we sought to test two hypotheses: 1) patients with PAH present impaired BRS during an orthostatic challenge; 2) the peripheral chemoreflex is sensitized in patients with PAH and contributes to cardiac autonomic modulation and BRS at rest and BRS during an orthostatic challenge. Twenty non‐hypoxemic patients with PAH and 10 healthy controls (CON) were assessed. Peripheral chemosensitivity was measured via the ventilatory response to transient inhalation of pure nitrogen. Beat‐by‐beat heart rate (ECG) and arterial pressure (finger photoplethismography) were measured at seated rest and during a repeated sit‐to‐stand maneuver (six consecutive repetitions of 10‐s sit and 10‐s stand), while participants randomly inhaled 100% of O2 to inhibit the peripheral chemoreflex tonic activity (i.e., hyperoxia), and 21% of O2 as control (i.e., normoxia). Isocapnia was maintained via a rebreathing system. Cardiac autonomic modulation was quantified via heart rate variability (HRV) indexes, which were calculated in time and frequency domains. The CBRS was calculated at rest via sequence and alpha index methods, and during a sit‐to‐stand maneuver via sequence method. The PAH group showed significantly higher peripheral chemosensitivity (PAH: 0.32 ± 0.04 vs CON: 0.18 ± 0.02 L/%SpO2, P < 0.05) and significantly lower CBRS during the sit‐to‐stand maneuver, compared to the CON group. Peripheral chemoreflex inhibition via hyperoxia similarly increased HRV and CBRS in both groups at rest. In addition, hyperoxia significantly increased BRS during the sit‐to‐stand maneuver only in the PAH group, and then, the BRS was normalized (i.e., attained the CON group level). In summary, this study provides novel evidence that patients with PAH present low CBRS during an orthostatic challenge. Furthermore, data supports that the peripheral chemoreflex is sensitized and tonically contributes to cardiac autonomic modulation in patients with PAH at rest, and most notably, to impaired cBRS during an orthostatic challenge.Support or Funding InformationThe study was supported by São Paulo Research Foundation, FAPESP (2015/221982; 2017/077713)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.