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
Bibliographic record
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 O 2 to inhibit the peripheral chemoreflex tonic activity (i.e., hyperoxia), and 21% of O 2 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 C BRS 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/%SpO 2 , P < 0.05) and significantly lower C BRS during the sit‐to‐stand maneuver, compared to the CON group. Peripheral chemoreflex inhibition via hyperoxia similarly increased HRV and C BRS 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 C BRS 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 Information The 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 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".