Septic impairment of capillary blood flow requires activated coagulation pathway and is reversed by ascorbate through eNOS‐dependent dislodging of platelets in capillaries
Bibliographic record
Abstract
Sepsis impairs capillary blood flow, leading to organ failure. We hypothesized that activation of the coagulation pathway in sepsis contributes to this impairment and that ascorbate reverses impairment by blocking the pathway. Sepsis in mice was induced by feces injection into peritoneum (FIP). Impaired flow in the hindlimb skeletal muscle was assessed with intravital microscopy. At time 0, mice were injected i.v. bolus of saline, platelet‐depleting Ab, P‐selectin blocking Ab or antithrombin, and then assessed at 6 h post‐FIP. Alternatively, eptifibatide (GPIIb/IIIa inhibitor) or ascorbate was injected at 6 h and impairment assessed at 7 h post‐FIP. In some mice, we injected rhodamine 6 G to view platelet and leukocyte adhesion in capillaries at 7 h. Sepsis impaired flow (complete stoppage) in 40 % of capillaries. In wild type mice, platelet depletion, P‐selectin blocking, antithrombin, eptifibatide, and ascorbate all reduced impairment to ~20 %. Sepsis increased the number of adhering platelets ~8 fold (the number of adhering leukocytes was negligible). Blocking of P‐selectin, eptifibatide, and ascorbate reduced this increase down to 3.2 ‐ 4.7 fold. Reduction in impairment and adhesion by ascorbate was not seen in eNOS‐/‐ mice. Thus, impairment of flow requires platelets, is inhibited by anticoagulants, and reversed by ascorbate through eNOS‐dependent dislodging of platelets in capillaries. (Support: HSFO)
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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 | 0.001 |
| 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".