Alterations in cutaneous microvascular function at high altitude in lowlanders and highlanders
Bibliographic record
Abstract
Microvascular function is impaired in lowlanders at high altitude; however, this impairment was gauged using post‐occlusive reactive hyperemia and the contribution of nitric oxide (NO) to cutaneous vasodilation at high altitude remains unknown. Low molecular O 2 at high altitude leads to production of reactive oxygen species (ROS) and reduced NO bioavailability. We therefore tested the hypothesis that vasodilation during a standard local heating protocol, and thus cutaneous microvascular function, is impaired in lowlanders at high altitude by ROS. We further tested whether lifelong residence at high altitude alters microvascular function compared to lowlanders. Four intradermal microdialysis membranes were inserted in the forearms of 11 male lowlanders [age: 30 (8) years; BMI: 24 (2) kg·m −2 ] at sea level and after two weeks at 4340 m in Cerro de Pasco, Peru. Andean highlanders [n=11; age: 26 (5) years; BMI: 24 (2) kg·m −2 ] residing permanently in Cerro de Pasco were also tested. The four sites were randomized and pre‐treated with infusions of 1) lactated Ringer's solution (control), 2) 100 μM Apocynin (NADPH oxidase inhibitor), 3) 10 μM Tempol (superoxide scavenger), and 4) 10 μM Allopurinol (xanthine oxidase inhibitor). Skin blood flux was measured continuously at each site via laser‐Doppler flowmetry during the 39°C local heating (NO‐dependent plateau phase), 20 mM L‐NAME (NO synthase inhibitor), and 44°C local heating combined with 28 mM sodium nitroprusside infusion to achieve maximal vasodilation. Data are presented as cutaneous vascular conductance (CVC; flux/mean arterial pressure) as a percentage of maximum. There was a main group effect (P<0.001) on CVC during 39°C heating with impaired vasodilation in both lowlanders at high altitude and in Andeans [control site: 54 (14) vs. 50 (24)%, respectively] compared to lowlanders at sea level [control site: 73 (19)%]. Similarly, the NO contribution to vasodilation during the 39°C plateau portion (i.e. effect of L‐NAME) was impaired (main group effect P<0.001) in lowlanders after 2 weeks at high altitude compared to sea level [control site: 41 (11) vs 49 (10)%, respectively], and this impairment was more pronounced in Andeans [control site: 32 (21)%]. There was no influence of ROS pathways, assessed via antioxidant infusions, on cutaneous vasodilation throughout the protocol in any group (all main drug effects P>0.05). When values were pooled from both groups and altitudes, local heating plateau CVC (r 2 =0.18, P=0.02) and the NO contribution to vasodilation (r 2 =0.13, P=0.04) were both positively correlated with oxygen‐hemoglobin saturation. These results indicate that high altitude impairs NO‐mediated vasodilation independent of a ROS mechanism but is associated with oxygen‐hemoglobin desaturation. The extent of microvascular impairment is greater in lifelong high altitude residents. Support or Funding Information Canada Research Chairs Program This abstract is from the Experimental Biology 2019 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 | 0.000 |
| 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".