Evidence map›Paper›PMID 41525029›Full record

ArticleCardiovascular drugs and therapy2026

Empagliflozin Supplementation in Cardioplegic Solution Improves Donor Heart Preservation by Maintaining Mitochondrial Homeostasis.

Rui-Lin Liu, Qing-Chun Song, Kai Yang, Lei Wang, Kai-Lu Jiao, Li Xie, Yi-Feng Yang

Abstract read
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Article in Cardiovascular drugs and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Impact of SGLT2 Inhibitors on Clinical Outcomes in Patients with Diabetes Mellitus Following Heart Transplantation: A Meta-analysis.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026
    Pooled it
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

7 authors.

Rui-Lin LiuDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, China.
Qing-Chun SongDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, China.
Kai YangDepartment of Plastic and Aestheticï (Burnï) Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Lei WangDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, China.
Kai-Lu JiaoDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, China.
Li XieDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, China.
Yi-Feng YangDepartment of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Central South University, Changsha, China. yyf627@csu.edu.cn.ORCID 0000-0003-3445-4214

Funding

National Science Foundation for Young Scientists of China 8150020951
6 · The paper itself

Abstract

backgroundProlonged cold ischemia and subsequent reperfusion are major causes of primary graft dysfunction in heart transplantation. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has shown cardioprotective effects in ischemia-reperfusion injury, but its role in donor heart preservation and the underlying mechanisms remain unexplored.

methodsWe evaluated the effects of empagliflozin supplementation in University of Wisconsin (UW) preservation solution using both in vitro and in vivo models. HL-1 cardiomyocytes were subjected to cold hypoxia/reoxygenation injury to simulate donor preservation conditions. A murine heterotopic heart transplantation model with 24-hour cold storage was used to assess graft function, myocardial injury, fibrosis, and immune response. Mechanistic studies were conducted using AMPK and Drp1 inhibitors to investigate mitochondrial signaling pathways.

resultsEmpagliflozin (500 nM) significantly improved cardiomyocyte viability, reduced apoptosis, and preserved mitochondrial membrane potential under cold hypoxia/reoxygenation stress. In vivo, empagliflozin-supplemented UW solution improved early graft contractility, attenuated myocardial injury, reduced serum injury markers, and alleviated histological damage and immune cell infiltration. Long-term follow-up revealed mitigation of chronic rejection, with reduced fibrosis, vasculopathy, and immune activation. Mechanistically, empagliflozin activated AMPK, inhibited Drp1 phosphorylation at Ser616, promoted mitochondrial fusion (Mfn1, OPA1), and preserved mitochondrial morphology. These protective effects were abolished by AMPK inhibition and restored by Drp1 inhibition, confirming AMPK-Drp1 pathway involvement.

conclusionsEmpagliflozin enhances donor heart preservation by mitigating cold ischemia-reperfusion injury through modulation of the AMPK-Drp1 signaling axis. This study extends the pharmacological profile of empagliflozin from metabolic regulation to donor heart preservation, highlighting its translational potential in clinical transplantation.

Indexed as

Benzhydryl CompoundsCardioplegic SolutionsGlucosidesHeart TransplantationMitochondria, HeartMyocardial Reperfusion InjuryMyocytes, CardiacOrgan PreservationOrgan Preservation SolutionsSodium-Glucose Transporter 2 InhibitorsAdenosineAllopurinolAMP-Activated Protein KinasesAnimalsApoptosisCell LineAdenosineAllopurinolAMP-Activated Protein KinasesBenzhydryl CompoundsCardioplegic SolutionsDnm1l protein, mouseDynaminsempagliflozinGlucosidesGlutathioneInsulinOrgan Preservation SolutionsRaffinoseSodium-Glucose Transporter 2 InhibitorsUniversity of Wisconsin-lactobionate solutionAMPK–Drp1 signalingDonor heart preservationEmpagliflozinHeart transplantationIschemia-reperfusion injuryMitochondrial dynamics

Identifiers

PMID41525029

What Socratic holds

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Registered trials

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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.