A study on the comparative and combinatorial efficacy of resveratrol with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker/neprilysin inhibitor in myocardial infarction
Bibliographic record
Abstract
Myocardial infarction (MI) and heart failure are the two major health care burdens around the world. Resveratrol, a plant polyphenol, is well-documented for its benefits in the setting of MI. However, it is also important to understand the comparative and combinatorial efficacy of resveratrol alongside the established therapies to translate the pre-clinical findings to the clinical setting. In the first study, left anterior descending coronary artery ligated (MI-induced) and sham-operated male Sprague Dawley rats were treated with vehicle, resveratrol, angiotensin-converting enzyme inhibitor perindopril, or a combination of both for 8 weeks. Echocardiography was performed to assess the cardiac structure and function. MI rats treated with resveratrol, perindopril and a combination of both had significantly reduced left ventricular (LV) dilatation and improved LV ejection fraction (LVEF). Resveratrol, perindopril and a combination of both significantly decreased cardiac oxidative stress, inflammation and fibrosis and improved the activity of antioxidant enzymes in MI rats. In the second study, MI-induced and sham-operated rats received vehicle, angiotensin receptor blocker/neprilysin inhibitor sacubitril/valsartan, angiotensin receptor blocker valsartan, resveratrol or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented LV dilatation and improved LVEF in MI rats. Resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol also significantly reduced oxidative stress, inflammation and brain natriuretic peptide in MI rats. In the final study, adult rat cardiomyocytes were pre-treated with resveratrol or left untreated and exposed to norepinephrine (NE). NE-exposure resulted in significant cardiomyocyte contractile dysfunction, reduced cell viability and an increase in oxidative stress. Resveratrol significantly improved contractile function and cell viability and reduced oxidative stress in NE-exposed adult rat cardiomyocytes. Pharmacological inhibition of superoxide dismutase (SOD) and Forkhead Box 1 (FOXO1) resulted in a loss of resveratrol mediated protection in NE-exposed adult rat cardiomyocytes. Resveratrol also prevented the proliferation of adult rat cardiac fibroblasts. In conclusion, resveratrol treatment improves cardiac structure and function equivalent to perindopril, valsartan, and sacubitril/valsartan in MI rats and the combination treatment is also effective. Resveratrol protects NE-exposed adult rat cardiomyocytes by a mechanism contingent upon SOD/FOXO1 and reduces cardiac fibroblast proliferation.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".