Evidence mapPaperPMID 41093005Full record

ArticleThe Journal of thoracic and cardiovascular surgery2026

Metformin's effects beyond ischemia: Evaluating cardioprotection in nonischemic myocardium in a large animal model of coronary and metabolic disease.

Keertana Yalamanchili, Christopher Stone, Kelsey C Muir, Dwight D Harris, Meghamsh Kanuparthy, Frank W Sellke

Abstract read
In one paragraph

Article in The Journal of thoracic and cardiovascular surgery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Keertana YalamanchiliDivision of Cardiothoracic Surgery, Department of Surgery, Brown University, Providence, RI.
Christopher StoneDivision of Cardiothoracic Surgery, Department of Surgery, Brown University, Providence, RI.
Kelsey C MuirDivision of Cardiothoracic Surgery, Department of Surgery, Brown University, Providence, RI.
Dwight D HarrisDivision of Cardiothoracic Surgery, Department of Surgery, Brown University, Providence, RI.
Meghamsh KanuparthyDivision of Cardiothoracic Surgery, Department of Surgery, Brown University, Providence, RI.
Frank W SellkeDivision of Cardiothoracic Surgery, Department of Surgery, Brown University, Providence, RI. Electronic address: fsellke@brownhealth.org.

Funding

CARDIOPLEGIA AND CORONARY MICROVASCULAR REACTIVITYR01HL046716 · BETH ISRAEL DEACONESS MEDICAL CENTER · 1997 to 2004
$1.5M
Vascular Dysfunction in Myocardial Ischemia and Metabolic SyndromeR01HL128831 · RHODE ISLAND HOSPITAL · 2025 to 2025
$818k
Cardiovascular Surgery Research TrainingT32HL160517 · RHODE ISLAND HOSPITAL · 2025 to 2025
$338k
NHLBI NIH HHS R01 HL046716NHLBI NIH HHS R01 HL128831NHLBI NIH HHS T32 HL160517
6 · The paper itself

Abstract

objectiveThis study evaluated the effects of metformin (MET) on nonischemic myocardium in a large animal model of coronary artery disease and metabolic syndrome (MS). Although prior work has shown MET improves perfusion and function in ischemic tissue, this study assessed whether its cardioprotective effects extend to nonischemic regions.

methodsYorkshire swine (n = 12) were fed a high-fat diet to induce MS and then underwent ameroid constrictor placement around the left circumflex artery to simulate coronary artery disease. Animals received either oral MET (1000 mg/day) or placebo for 7 weeks. Regional myocardial perfusion was assessed via microsphere injections at rest and during pacing. Nonischemic myocardial tissue was identified using gold microsphere distribution and analyzed using immunoblotting, immunofluorescence, and hemodynamic assessment. Statistical significance was evaluated using Student t test or the Mann Whitney U test.

resultsDespite no significant changes in perfusion, MET-treated animals demonstrated significantly reduced apoptotic markers (caspase 9, cleaved caspase 9, apoptosis-inducing factor, and Bcl2-associated agonist of cell death (BAD); P < .05) and increased phosphorylated BAD/BAD ratios. Prosurvival signaling was enhanced with elevated phosphorylated protein kinase B (AKT)/AKT, phosphorykated mammalian target of rapamycin (mTOR)/mTOR, and phosphorylated AMP-activated protein kinase (AMPK)/AMPK ratios (P < .05). Tansferase dUTP nick end labeling staining confirmed decreased apoptosis histologically. Functionally, MET improved cardiac output, stroke volume, and maximum derivative of volume in the myocardium (P < .05), correlating with reductions in apoptotic signaling.

conclusionsMET was associated with significantly reduced apoptosis and promoted prosurvival signaling in nonischemic myocardium without altering perfusion. These findings suggest that MET's cardioprotective effects are not limited to ischemic tissue, highlighting its potential role as a systemic therapy for coronary artery disease and metabolic syndrome, including as an adjunct in cardiac surgery.

Indexed as

Cardiotonic AgentsCoronary Artery DiseaseMetabolic SyndromeMetforminMyocardiumAnimalsApoptosisCoronary CirculationDiet, High-FatDisease Models, AnimalSignal TransductionSus scrofaSwineCardiotonic AgentsMetformincoronary artery diseasemetabolic syndromemetforminnonischemic myocardium

Identifiers

PMID41093005
PMCPMC13264963

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.