Angiotensin Receptor Neprilysin Inhibitor Attenuates Myocardial Remodeling and Improves Infarct Perfusion in Experimental Heart Failure
Bibliographic record
Abstract
Abstract Angiotensin receptor blocker-neprilysin inhibitor (ARNi) therapy improves the prognosis of heart failure patients. However, the mechanisms remain unclear. This study investigated the biological effects of ARNi with neprilysin inhibitor sacubitril and angiotensin receptor blocker valsartan on myocardial remodeling and cardiac perfusion in experimental heart failure (HF) after myocardial infarction (MI). Male Lewis rats (10-weeks old) with confirmed HF were randomized one-week post-MI to treatment with vehicle (water), sacubitril/valsartan or valsartan, as comparator group, for either 1 or 5 weeks. Sacubitril/valsartan for 1-week limited LV contractile dysfunction vs. vehicle and both sacubitril/valsartan and valsartan attenuated progressive LV dilation after 1 and 5 weeks treatment. After 5 weeks, both sacubitril/valsartan and valsartan reduced CTGF expression in the remote myocardium, although only sacubitril/valsartan prevented interstitial fibrosis. In the border zone, sacubitril/valsartan and valsartan reduced hypertrophic markers, but only sacubitril/valsartan reduced cardiomyocyte size and increased VEGFA expression. In the infarct, sacubitril/valsartan induced an early uptake of 99m Tc-NC100692 (a radiotracer of angiogenesis) and improved perfusion, as determined by 201 Tl microSPECT/CT imaging. In conclusion, ARNi improved global LV function, limited remodeling in the remote and border zones, and increased perfusion to the infarct. Sacubitril/valsartan had more consistent effects than valsartan on LV remodeling in experimental HF.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".