Contrasting Reflex Neural Modulation of Muscle Sympathetic Nerve Activity at Rest and During One‐leg Dynamic Exercise in Subjects with and without Heart Failure
Bibliographic record
Abstract
We previously showed that muscle sympathetic nerve activity (MSNA) is augmented at rest in patients with heart failure due to reduced ejection fraction (HFrEF), and rises further during mild and moderate dynamic 1‐leg exercise in stark contrast to the drop observed in healthy controls at similar exercise intensities. The reflex mechanisms responsible for this unique response are unknown. We hypothesized that MSNA may be reduced at rest and during exercise in HFrEF by either: 1) stimulating the sympatho‐inhibitory cardiopulmonary baroreceptors by exercising supine rather than upright; or 2) inhibiting the sympatho‐excitatory peripheral chemoreceptors by breathing 32% oxygen (O 2 ). We studied 6 stable, non‐diabetic, medicated HFrEF men ( mean age 58 ± 3 SE [range 46 to 65] years; mean left ventricular ejection fraction 29 ± 4% [range 15–38]); of either ischemic (n=5) or non‐ischemic (n=1) etiology; plus 6 healthy, age matched, medication‐free volunteers (3 women; mean age 58 ± 3 [range 49 to 72]). We assessed peak oxygen uptake (VO 2peak ) by open‐circuit spirometry. On a separate day, fibular MSNA (microneurography) was measured at rest and during upright 1‐leg cycling (2 min each unloaded and at 50% of VO 2peak ). The identical cycling protocol was then repeated during supine exercise (n=5 HFrEF) and again during upright cycling while breathing 32% O 2 (n=4 HFrEF). Heart rate and diastolic blood pressure were similar across interventions in both groups but systolic blood pressure was significantly lower in HFrEF vs controls (main effect P=0.01). MSNA was reduced at rest only while supine in control subjects (main effect P=0.01; P=0.01 vs upright). Whereas in HFrEF, both supine posture and supplemental O 2 attenuated MSNA burst frequency at rest (main effect P=0.01; P=0.02 vs upright). During exercise, MSNA burst frequency progressively decreased in healthy controls particularly during unloaded cycling (main effect of time P<0.001), and tended to be lower throughout supine cycling (P=0.06 vs upright). By contrast, in HFrEF patients, there was no significant change in MSNA burst frequency during exercise while supine nor with supplemental oxygen (main effect of intervention P=0.51; time P=0.34). Thus, both at rest and during mild cycling exercise, supine posture augments the sympathoinhibitory response in control subjects. However in HFrEF patients, sympathoexcitation at rest can be reduced to a similar extent by either triggering the inhibitory cardiopulmonary baroreflex or abolishing arterial chemoreceptor activation with no further effect during exercise. Support or Funding Information Supported by Heart and Stroke Foundation of Ontario and Canadian Institutes for Health Research
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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 | 0.000 |
| 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".