Repeated daily dosing with sildenafil provides sustained protection from endothelial dysfunction caused by ischemia and reperfusion: a human in vivo study
Bibliographic record
Abstract
Sildenafil and nitroglycerin (GTN) are effective pharmacological preconditioning agents, protecting from the adverse effects of ischemia and reperfusion (I/R). The objective of the present study was to determine whether repeated, daily administration of sildenafil or GTN provides sustained preconditioning from I/R in the human forearm vasculature. Thirty-six healthy volunteers participated in this investigator-blind, randomized, placebo-controlled trial. Subjects received transdermal GTN (0.6 mg/h, 2 h/day), sildenafil (50 mg once daily), or placebo. Twenty-four hours after the first dose of medication, subjects underwent an assessment of flow-mediated dilation (FMD) before and after I/R (15 min of upper arm ischemia followed by 15 min of reperfusion). Subjects continued their study medication for 7 days, at which point FMD measurements were repeated before and after I/R. Venous blood samples were obtained for the determination of myeloperoxidase, P-selectin, and myoglobin before and after each I/R episode. Twenty-four hours after the first dose, both sildenafil and GTN (but not placebo) provided protection from the adverse effects of I/R. After 7 days of repeated daily doses and 24 h after the last dose, FMD was significantly blunted after I/R in placebo- and GTN-treated groups. In contrast, repeated daily administration of sildenafil provided continued protection from the adverse effects of I/R on endothelial function. There was no significant change in plasma levels of myeloperoxidase, P-selectin, or myoglobin at any time point. In conclusion, the present study establishes, for the first time in humans, that sildenafil, but not GTN, provides sustained pharmacological preconditioning of the endothelium and protection from adverse I/R effects on vascular function.
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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 | 0.002 | 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 | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".