Global REACH 2018: heightened α‐adrenergic signaling restrains blood flow to precisely match oxygen delivery and demand during handgrip exercise in Andeans with polycythemia
Bibliographic record
Abstract
Introduction Populations suffering from polycythemia such as polycythemia vera, Chuvash polycythemia, and chronic mountain sickness (CMS) suffer exercise fatigue and reduced exercise capacity. Potential mechanisms for reduced exercise capacity include the negative influences of high hematocrit, elevated blood viscosity, and increased sympathetic activity on convective and diffusive oxygen transport. However, it remains unclear how sympathetic activity impacts blood flow during isolated forearm exercise in Andeans suffering with polycythemia. Purpose Therefore, using the isolated forearm handgrip model, the present study sought to examine the role of α‐adrenergic vasoconstrictor signaling in regulating skeletal muscle vasodilator function in seven Andeans with polycythemia (CMS+; n=7) and nine of their healthy townsmen (CMS‐; n=9) living at ~4350m. Methods Forearm blood flow (FBF; Doppler ultrasound), mean arterial pressure (MAP, intra‐arterial catheter), and changes in forearm vascular conductance (∆FVC), calculated via FBF and MAP, were measured at rest and during graded handgrip exercise (HGE; 5, 15, 25% maximal voluntary contraction; MVC), before and after local +α‐β adrenergic blockade (phentolamine; propranolol). Blood samples were taken via arterial and venous catheter at rest and each stage of handgrip exercise to determine oxygen delivery, uptake, and extraction. All data are quantified as mean±SD. Results During the control trial, progressive HGE increased FVC (CMS‐: P<0.01; CMS+: P<0.01), oxygen delivery (CMS‐: P<0.01; CMS+: P<0.01) and extraction (CMS‐: P<0.01; CMS+: P<0.01) similarly in both CMS‐ and CMS+ Andeans. However, after +α‐β adrenergic blockade, the FVC response to HGE at 25% was greater in CMS+ (∆FVC: control: 92.8±31.1 vs. +α‐β blockade: 137.5±66.7 ml·min ‐1 ·100mmHg ‐1 ; P<0.01) whereas the FVC response remained unchanged in CMS‐ (∆FVC: control: 109.0±32.8 vs. +α‐β blockade: 95.5±57.9 ml·min ‐1 ·100mmHg ‐1 ; P=0.15). In CMS+, increased FVC during +α‐β adrenergic blockade also increased oxygen delivery during 25% HGE (∆DO 2 : control: 21.9±5.9 vs. +α‐β blockade: 29.7±9.9 ml·min ‐1 ; P<0.01); however, oxygen extraction remained unchanged (∆a‐VO 2 : control: 9.6±4.7 vs. +α‐β blockade: 8.3±4.1 ml·dl ‐1 ; P=0.46). Conclusion CMS+ individuals demonstrate heightened α‐adrenergic restraint of vasodilation during HGE. However, oxygen uptake in the forearm during exercise remains intact due to elevated arterial oxygen content from increased hemoglobin. Perhaps, a phenotypical trade‐off to polycythemia; whereby heightened vasoconstrictor signaling restrains blood flow to match the needed metabolic demand, or elevated whole blood viscosity elicits greater shear signaling requiring higher sympathetic restraint.
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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) | 0.002 | 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".