Abstract 5521: Rosuvastatin Prevents Ischemia and Reperfusion-Induced Endothelial Dysfunction by a COX-2 Dependent Mechanism
Bibliographic record
Abstract
BACKGROUND: Animal studies have demonstrated that rosuvastatin (RSV) can limit the damage induced by ischemia-reperfusion (IR) in the cardiac, cerebral and mesenteric circulation. It remains unknown whether this beneficial effect of RSV can also be demonstrated in humans, and by what mechanism this may occur. METHODS AND RESULTS: Twenty healthy volunteers were randomized to a single dose of oral RSV (40 mg) or placebo. 24 hours later, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). There was no difference in pre-IR FMD between groups (P=NS). In the placebo group, FMD was significantly blunted after IR (FMD pre-IR: 6.4+/−0.4%, post-IR: 1.1+/−1.2%, P<0.01). This impairment in FMD with IR was prevented with RSV (Table ; FMD before IR: 7.5+/−1.0%; after IR: 6.2+/−1.2%, P =NS compared with RSV before IR; P<0.05 vs. placebo). In a separate protocol, 18 healthy volunteers received the cyclooxygenase-2 (COX-2) inhibitor celecoxib (200mg BID p.o.) for 5 days. On day 4, subjects were randomized to a single dose of RSV (40mg) or placebo and 24 hours later underwent the same protocol as above. Pretreatment with celecoxib completely abolished RSV’s protective effect (Table ; FMD pre-IR: 8.0±2.2%, post-IR: 1.4±2.0%, P<0.001 before versus after IR, P=NS vs. placebo). IR did not modify resting arterial diameter, baseline blood flow or peak hyperemic blood flow during FMD in either protocol (Table ; P=NS for all). CONCLUSIONS: The present findings demonstrate, for the first time in humans, the ability of RSV to pharmacologically prevent the development of IR-induced endothelial dysfunction. In addition, these data demonstrate the importance of COX-2 in the manifestation of this preconditioned phenotype, evidence that also provides potential mechanistic insight into the observed cardiovascular toxicity with COX-2 inhibitors.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".