Application of a Second‐Order Control‐Systems Model to Investigate Effects of Impaired Capillary Signalling in Skeletal Muscle on Regulation of Capillary Blood Flow Velocity and Tissue Oxygenation
Bibliographic record
Abstract
Microcirculation is the main region of the vasculature where oxygen (O 2 ) is transferred directly from blood to metabolically active tissue. Tissue O 2 partial pressure (PO 2 ) in the microcirculation has been historically infeasible to measure, but critical as an indicator of capillary and surrounding tissue health. Thus, theoretical modelling of capillary‐tissue O 2 transport is crucial as a complement to in vivo experiments in exploring structure‐function relationships in microvascular networks (Ellis et al, Microcirc 2012 , 19:5). To properly complement experiments which stimulate O 2 flow‐dependent regulation systems, modelling of microcirculatory O 2 transport requires incorporation of knowledge on regulatory mechanisms. Capillary networks modulate their blood velocity to recruit sufficient O 2 delivery in many local O 2 conditions; this has led to the conclusion that endothelium signals upstream to arterioles in an O 2 ‐dependent manner (Ghonaim et al, Microcirc 2021 , e12699). Recently, a second‐order control systems model was developed to investigate the interaction between capillary‐tissue O 2 transport and O 2 ‐dependent blood flow regulation under an externally applied O 2 stimulus. This utilized elements from previous arteriolar diameter alteration models in response to skeletal muscle O 2 gradients, as well as elements from a recently developed continuous‐capillary O 2 transport model (Afas et al, Math Biosci 2021 , 333:108535). The control systems model aimed to predict modulations in blood velocity through endothelial signalling which homogenized outlet capillary PO 2 in skeletal muscle. The model demonstrated that variations in O 2 transport parameters such as capillary network density and tissue O 2 consumption rate had varying effects on the averaged blood velocity in a small skeletal muscle segment perfused by a capillary network. In addition, the externally supplied PO 2 had an effect on both blood velocity and the tissue‐capillary O 2 balance. While the tissue‐capillary PO 2 balance and velocity adaptation were investigated, the endothelial signalling parameters were not reported (Afas & Goldman, Vasc. Bio. 2021 , conference). The present study investigates implications of capillary network metric variations on the endothelial signal communicated upstream to modulate capillary blood flow in response to various muscle surface PO 2 levels. Constraints imposed by pathogenic impairment of endothelial signalling will be investigated and interpreted in the context of capillary flow regulation.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".