Daily Ischemic Preconditioning Provides Sustained Protection From Ischemia–Reperfusion Induced Endothelial Dysfunction: A Human Study
Bibliographic record
Abstract
BACKGROUND: It is well established that acute ischemic preconditioning (IPC) protects against ischemia-reperfusion (IR) injury; however, the effectiveness of repeated IPC exposure has not been extensively investigated. We aimed to determine whether daily IPC episodes provide continued protection from IR injury in a human forearm model, and the role of cyclooxygenase-2 in these responses. METHODS AND RESULTS: Thirty healthy volunteers were randomized to participate in 2 of 3 protocols (IR alone, 1-day IPC, 7-day IPC) in an operator-blinded, crossover design. Subjects in the IR alone protocol underwent flow-mediated dilation (FMD) measurements pre- and post-IR (15' upper-arm ischemia and 15' reperfusion). The 1-day IPC protocol involved FMD measurements before and after 1 episode of IPC (3 cycles of 5' upper-arm ischemia and 5' reperfusion) and IR. Day 7 of the 7-day IPC protocol was identical to the 1-day IPC protocol but was preceded by single daily episodes of IPC for 6 days prior. During each protocol, subjects received a 7-day treatment of either the cyclooxygenase-2 inhibitor celecoxib or placebo. Pre-IR FMD was similar between groups. IR alone reduced FMD post-IR (placebo, ΔFMD: -4.4±0.7%; celecoxib, ΔFMD: -5.0±0.5%). One-day IPC completely prevented this effect (placebo, ΔFMD: -1.1±0.6%; celecoxib, ΔFMD: 0.0±0.7%; P<0.0001). Similarly, 7-day IPC demonstrated persistent endothelial protection post-IR (placebo, ΔFMD: -0.9±0.9%; celecoxib, ΔFMD: 0.0±0.8%; P<0.0001, P<0.0001 for ANOVA effect of IPC protocol). Celecoxib did not alter responses to IR in any protocol. CONCLUSIONS: Daily episodes of IPC provide sustained protection from IR-induced endothelial dysfunction in humans through a mechanism that appears cyclooxygenase-2-independent.
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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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".