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Volume 20, Issue 1
  • ISSN: 2772-4328
  • E-ISSN: 2772-4336

Abstract

Introduction

In this study, a meta-analysis was conducted to investigate the therapeutic effect of Dapagliflozin (DAPA) on animals suffering from myocardial ischemia reperfusion compared to the group that did not receive treatment.

Methods

According to the inclusion and exclusion criteria two researchers performed the primary and secondary screening based on the title abstract and full text. After data extraction, meta-analysis was performed using STATA software. Standardized mean differences were used to analyze the results of the reported studies. Subgroup analysis and quality control of articles were also conducted.

Results

A total of 21 separate experiments showed that DAPA increased mean fractional shortening (%FS) and ejection fraction (%EF) compared to the untreated animals. A significant reduction in the weight and size of the infarcted area and significant increases in dp/dt+, dp/dt-, left ventricular end-systolic internal dimensions (LVIDs), left ventricular end-diastolic internal dimensions (LVIDd), Volume systole and Volume diastole were observed in treated animals.

Conclusion

DAPA has the potential to become a candidate for the treatment of post-ischemic heart damage, pending animal and human studies to validate this.

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2025-03-07

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References

  1. LiZ. WangK. DingY. Dapagliflozin modulates the faecal microbiota after myocardial infarction in non‐diabetic mice.Clin. Exp. Pharmacol. Physiol.2023501688110.1111/1440‑1681.13727 36164968
     [Google Scholar]
  2. AhmadiA. SooriH. MehrabiY. EtemadK. SamavatT. KhaledifarA. Incidence of acute myocardial infarction in Islamic Republic of Iran: A study using national registry data in 2012.EMHJ201521118
     [Google Scholar]
  3. HausenloyD.J. YellonD.M. Myocardial ischemia-reperfusion injury: A neglected therapeutic target.J. Clin. Invest.201312319210010.1172/JCI62874 23281415
     [Google Scholar]
  4. HeJ. Treatment of myocardial ischaemia-reperfusion injury in patients with ST-segment elevation myocardial infarction: Promise, disappointment, and hope.Rev. Cardiovasc. Med.202223123
     [Google Scholar]
  5. GerczukP.Z. KlonerR.A. An update on cardioprotection: A review of the latest adjunctive therapies to limit myocardial infarction size in clinical trials.J. Am. Coll. Cardiol.2012591196997810.1016/j.jacc.2011.07.054 22402067
     [Google Scholar]
  6. BraunwaldE. KlonerR.A. Myocardial reperfusion: A double-edged sword?J. Clin. Invest.19857651713171910.1172/JCI112160 4056048
     [Google Scholar]
  7. NeriM. RiezzoI. PascaleN. PomaraC. TurillazziE. Ischemia/reperfusion injury following acute myocardial infarction: A critical issue for clinicians and forensic pathologists.Mediators Inflamm.2017201711410.1155/2017/7018393 28286377
     [Google Scholar]
  8. SagrisM. ApostolosA. TheofilisP. Myocardial ischemia–reperfusion injury: Unraveling pathophysiology, clinical manifestations, and emerging prevention strategies.Biomedicines202412480210.3390/biomedicines12040802 38672157
     [Google Scholar]
  9. FrankA. BonneyM. BonneyS. WeitzelL. KoeppenM. EckleT. Myocardial ischemia reperfusion injury: From basic science to clinical bedside.Semin. Cardiothorac. Vasc. Anesth.201216312313210.1177/1089253211436350 22368166
     [Google Scholar]
  10. PerrelliM.G. PagliaroP. PennaC. Ischemia/reperfusion injury and cardioprotective mechanisms: Role of mitochondria and reactive oxygen species.World J. Cardiol.20113618620010.4330/wjc.v3.i6.186 21772945
     [Google Scholar]
  11. GrangerD.N. KvietysP.R. Reperfusion injury and reactive oxygen species: The evolution of a concept.Redox Biol.2015652455110.1016/j.redox.2015.08.020 26484802
     [Google Scholar]
  12. CadenasS. AragonésJ. Landázuri MO. Mitochondrial reprogramming through cardiac oxygen sensors in ischaemic heart disease.Cardiovasc. Res.201088221922810.1093/cvr/cvq256 20679415
     [Google Scholar]
  13. AfzalS. Abdul ManapA.S. AttiqA. AlbokhadaimI. KandeelM. AlhojailyS.M. From imbalance to impairment: The central role of reactive oxygen species in oxidative stress-induced disorders and therapeutic exploration.Front. Pharmacol.202314126958110.3389/fphar.2023.1269581 37927596
     [Google Scholar]
  14. ChaudharyP. JanmedaP. DoceaA.O. Oxidative stress, free radicals and antioxidants: Potential crosstalk in the pathophysiology of human diseases.Front Chem.202311115819810.3389/fchem.2023.1158198 37234200
     [Google Scholar]
  15. ChenW. ZhangY. WangZ. Dapagliflozin alleviates myocardial ischemia/reperfusion injury by reducing ferroptosis via MAPK signaling inhibition.Front. Pharmacol.202314107820510.3389/fphar.2023.1078205 36891270
     [Google Scholar]
  16. YuY.W. QueJ.Q. LiuS. Sodium-glucose co-transporter-2 inhibitor of dapagliflozin attenuates myocardial ischemia/reperfusion injury by limiting NLRP3 inflammasome activation and modulating autophagy.Front. Cardiovasc. Med.2022876821410.3389/fcvm.2021.768214 35083298
     [Google Scholar]
  17. DasF. BeraA. Ghosh-ChoudhuryN. High glucose-stimulated enhancer of zeste homolog-2 (EZH2) forces suppression of deptor to cause glomerular mesangial cell pathology.Cell. Signal.20218611007210.1016/j.cellsig.2021.110072 34224844
     [Google Scholar]
  18. Abdul-GhaniM.A. NortonL. DeFronzoR.A. Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus.Am. J. Physiol. Renal Physiol.201530911F889F90010.1152/ajprenal.00267.2015 26354881
     [Google Scholar]
  19. MiyataK.N. ZhangS.L. ChanJ.S.D. The rationale and evidence for SGLT2 inhibitors as a treatment for nondiabetic glomerular disease.Glomerular Dis.202111213310.1159/000513659 36751486
     [Google Scholar]
  20. PageM.J. McKenzieJ.E. BossuytP.M. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.Syst. Rev.20211018910.1186/s13643‑021‑01626‑4 33781348
     [Google Scholar]
  21. HooijmansC.R. RoversM.M. de VriesR.B.M. LeenaarsM. Ritskes-HoitingaM. LangendamM.W. SYRCLE’s risk of bias tool for animal studies.BMC Med. Res. Methodol.20141414310.1186/1471‑2288‑14‑43 24667063
     [Google Scholar]
  22. FanZ. XuY. ChenX. JiM. MaG. Appropriate dose of dapagliflozin improves cardiac outcomes by normalizing mitochondrial fission and reducing cardiomyocyte apoptosis after acute myocardial infarction.Drug Des. Devel. Ther.2022162017203010.2147/DDDT.S371506 35789742
     [Google Scholar]
  23. GongL. The co-treatment of rosuvastatin with dapagliflozin synergistically inhibited apoptosis via activating the PI3K/AKt/mTOR signaling pathway in myocardial ischemia/reperfusion injury rats. Open Med2021104757
     [Google Scholar]
  24. LahnwongC. PaleeS. ApaijaiN. Acute dapagliflozin administration exerts cardioprotective effects in rats with cardiac ischemia/reperfusion injury.Cardiovasc. Diabetol.20201919110.1186/s12933‑020‑01066‑9 32539724
     [Google Scholar]
  25. LeeC.C. ChenW.T. ChenS. LeeT.M. Dapagliflozin attenuates arrhythmic vulnerabilities by regulating connexin43 expression via the AMPK pathway in post-infarcted rat hearts.Biochem. Pharmacol.202119211467410.1016/j.bcp.2021.114674 34252408
     [Google Scholar]
  26. LeeT.M. ChangN.C. LinS.Z. Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts.Free Radic. Biol. Med.201710429831010.1016/j.freeradbiomed.2017.01.035 28132924
     [Google Scholar]
  27. MaL. ZouR. ShiW. SGLT2 inhibitor dapagliflozin reduces endothelial dysfunction and microvascular damage during cardiac ischemia/reperfusion injury through normalizing the XO-SERCA2-CaMKII-coffilin pathways.Theranostics202212115034505010.7150/thno.75121 35836807
     [Google Scholar]
  28. MaS. ChenL. YanJ. Dapagliflozin attenuates residual cardiac remodeling after surgical ventricular reconstruction in mice with an enlarged heart after myocardial infarction.Biomed. Pharmacother.202215611376510.1016/j.biopha.2022.113765 36228368
     [Google Scholar]
  29. TsaiK.L. HsiehP.L. ChouW.C. ChengH.C. HuangY.T. ChanS.H. Dapagliflozin attenuates hypoxia/reoxygenation-caused cardiac dysfunction and oxidative damage through modulation of AMPK.Cell Biosci.20211114410.1186/s13578‑021‑00547‑y 33637129
     [Google Scholar]
  30. WangK. LiZ. SunY. Dapagliflozin improves cardiac function, remodeling, myocardial apoptosis, and inflammatory cytokines in mice with myocardial infarction.J. Cardiovasc. Transl. Res.202215478679610.1007/s12265‑021‑10192‑y 34855147
     [Google Scholar]
  31. ChenR. ZhangY. ZhangH. SGLT2 inhibitor dapagliflozin alleviates intramyocardial hemorrhage and adverse ventricular remodeling via suppressing hepcidin in myocardial ischemia-reperfusion injury.Eur. J. Pharmacol.202395017572910.1016/j.ejphar.2023.175729 37100110
     [Google Scholar]
  32. ZuoW. WangL. TianR. Dapagliflozin alleviates myocardial ischaemia reperfusion injury by activating mitophagy via the AMPK-PINK1/parkin signalling pathway.Curr. Vasc. Pharmacol.2023 38141195
     [Google Scholar]
  33. PengY. GuoM. LuoM. Dapagliflozin ameliorates myocardial infarction injury through AMPKα-dependent regulation of oxidative stress and apoptosis.Heliyon2024107e2916010.1016/j.heliyon.2024.e29160 38617915
     [Google Scholar]
  34. ConnellyK.A. ZhangY. DesjardinsJ.F. ThaiK. GilbertR.E. Dual inhibition of sodium–glucose linked cotransporters 1 and 2 exacerbates cardiac dysfunction following experimental myocardial infarction.Cardiovasc. Diabetol.20181719910.1186/s12933‑018‑0741‑9 29981571
     [Google Scholar]
  35. SugiyamaS. JinnouchiH. KurinamiN. Dapagliflozin reduces fat mass without affecting muscle mass in type 2 diabetes.J. Atheroscler. Thromb.201825646747610.5551/jat.40873 29225209
     [Google Scholar]
  36. NovikovA. VallonV. Sodium glucose cotransporter 2 inhibition in the diabetic kidney.Curr. Opin. Nephrol. Hypertens.2016251505810.1097/MNH.0000000000000187 26575393
     [Google Scholar]
  37. ThomsonS.C. VallonV. Renal effects of sodium-glucose co-transporter inhibitors.Am. J. Cardiol.2019124Suppl. 1S28S35
     [Google Scholar]
  38. NiL. YuanC. ChenG. ZhangC. WuX. SGLT2i: Beyond the glucose-lowering effect.Cardiovasc. Diabetol.20201919810.1186/s12933‑020‑01071‑y 32590982
     [Google Scholar]
  39. ChoY.K. KimY.J. JungC.H. Effect of sodium-glucose cotransporter 2 inhibitors on weight reduction in overweight and obese populations without diabetes: A systematic review and a meta-analysis.J. Obes. Metab. Syndr.202130433634410.7570/jomes21061 34897070
     [Google Scholar]
  40. AndreadouI. BellR.M. Bøّtker HE, Zuurbier CJ. SGLT2 inhibitors reduce infarct size in reperfused ischemic heart and improve cardiac function during ischemic episodes in preclinical models.Biochim. Biophys. Acta Mol. Basis Dis.20201866716577010.1016/j.bbadis.2020.165770 32194159
     [Google Scholar]
  41. Sjöström CD, Johansson P, Ptaszynska A, List J, Johnsson E. Dapagliflozin lowers blood pressure in hypertensive and non-hypertensive patients with type 2 diabetes.Diab. Vasc. Dis. Res.201512535235810.1177/1479164115585298 26008804
     [Google Scholar]
  42. HsiehP.L. ChuP.M. ChengH.C. Dapagliflozin mitigates doxorubicin-caused myocardium damage by regulating AKT-mediated oxidative stress, cardiac remodeling, and inflammation.Int. J. Mol. Sci.202223171014610.3390/ijms231710146 36077544
     [Google Scholar]
  43. SaleemF. Dapagliflozin: Cardiovascular safety and benefits in type 2 diabetes mellitus.Cureus2017910e175110.7759/cureus.1751 29226041
     [Google Scholar]
  44. SonessonC. JohanssonP.A. JohnssonE. Gause-NilssonI. Cardiovascular effects of dapagliflozin in patients with type 2 diabetes and different risk categories: A meta-analysis.Cardiovasc. Diabetol.20161513710.1186/s12933‑016‑0356‑y 26895767
     [Google Scholar]
  45. CowieM.R. FisherM. SGLT2 inhibitors: Mechanisms of cardiovascular benefit beyond glycaemic control.Nat. Rev. Cardiol.2020171276177210.1038/s41569‑020‑0406‑8 32665641
     [Google Scholar]
  46. SoliniA. GianniniL. SeghieriM. Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: A pilot study.Cardiovasc. Diabetol.201716113810.1186/s12933‑017‑0621‑8 29061124
     [Google Scholar]
  47. HasanA. MenonS.N. ZerinF. HasanR. Dapagliflozin induces vasodilation in resistance-size mesenteric arteries by stimulating smooth muscle cell KV7 ion channels.Heliyon202285e0950310.1016/j.heliyon.2022.e09503 35647331
     [Google Scholar]
  48. LopaschukG.D. VermaS. Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors: A state-of-the-art review.JACC Basic Transl. Sci.20205663264410.1016/j.jacbts.2020.02.004 32613148
     [Google Scholar]
  49. BoschA. OttC. JungS. How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial.Cardiovasc. Diabetol.20191814410.1186/s12933‑019‑0839‑8 30922297
     [Google Scholar]
  50. HasanR. LaskerS. HasanA. Canagliflozin ameliorates renal oxidative stress and inflammation by stimulating AMPK–Akt–eNOS pathway in the isoprenaline-induced oxidative stress model.Sci. Rep.20201011465910.1038/s41598‑020‑71599‑2 32887916
     [Google Scholar]
  51. WiviottS.D. RazI. BonacaM.P. Dapagliflozin and cardiovascular outcomes in type 2 diabetes.N. Engl. J. Med.2019380434735710.1056/NEJMoa1812389 30415602
     [Google Scholar]
  52. SogaF. TanakaH. TatsumiK. Impact of dapagliflozin on left ventricular diastolic function of patients with type 2 diabetic mellitus with chronic heart failure.Cardiovasc. Diabetol.201817113210.1186/s12933‑018‑0775‑z 30296931
     [Google Scholar]
  53. SearaF.A.C. MacielL. BarbosaR.A.Q. Cardiac ischemia/reperfusion injury is inversely affected by thyroid hormones excess or deficiency in male Wistar rats.PLoS One2018131e019035510.1371/journal.pone.0190355 29304184
     [Google Scholar]
  54. FerranniniE. BaldiS. FrascerraS. Renal handling of ketones in response to sodium–glucose cotransporter 2 inhibition in patients with type 2 diabetes.Diabetes Care201740677177610.2337/dc16‑2724 28325783
     [Google Scholar]
  55. MazerC.D. HareG.M.T. ConnellyP.W. Effect of empagliflozin on erythropoietin levels, iron stores, and red blood cell morphology in patients with type 2 diabetes mellitus and coronary artery disease.Circulation2020141870470710.1161/CIRCULATIONAHA.119.044235 31707794
     [Google Scholar]
  56. DhillonS. Dapagliflozin: A review in type 2 diabetes.Drugs201979101135114610.1007/s40265‑019‑01148‑3 31236801
     [Google Scholar]
  57. EkanayakeP. MudaliarS. Increase in hematocrit with SGLT-2 inhibitors - Hemoconcentration from diuresis or increased erythropoiesis after amelioration of hypoxia?Diabetes Metab. Syndr.202317210270210.1016/j.dsx.2022.102702 36657305
     [Google Scholar]
  58. VallonV. VermaS. Effects of SGLT2 inhibitors on kidney and cardiovascular function.Annu. Rev. Physiol.202183150352810.1146/annurev‑physiol‑031620‑095920 33197224
     [Google Scholar]
  59. ZhangY. LinX. ChuY. Dapagliflozin: A sodium–glucose cotransporter 2 inhibitor, attenuates angiotensin II-induced cardiac fibrotic remodeling by regulating TGFβ1/Smad signaling.Cardiovasc. Diabetol.202120112110.1186/s12933‑021‑01312‑8 34116674
     [Google Scholar]
  60. AyadaC. Toru Ü, Korkut Y. The relationship of stress and blood pressure effectors.Hippokratia201519299108 27418756
     [Google Scholar]
  61. Leite-MoreiraA.F. Current perspectives in diastolic dysfunction and diastolic heart failure.Heart200692571271810.1136/hrt.2005.062950 16614298
     [Google Scholar]
  62. RosséT. OlivierR. MonneyL. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c.Nature1998391666649649910.1038/35160 9461218
     [Google Scholar]
  63. HataA.N. EngelmanJ.A. FaberA.C. The BCL2 family: Key mediators of the apoptotic response to targeted anticancer therapeutics.Cancer Discov.20155547548710.1158/2159‑8290.CD‑15‑0011 25895919
     [Google Scholar]
  64. DanialN.N. BCL-2 family proteins: Critical checkpoints of apoptotic cell death.Clin. Cancer Res.200713247254726310.1158/1078‑0432.CCR‑07‑1598 18094405
     [Google Scholar]
  65. SongB. ZhangH. ZhouB. Effects of Dapagliflozin on myocardial remodeling, inflammatory factors, and cardiac events in heart failure with preserved ejection fraction.Naunyn Schmiedebergs Arch. Pharmacol.20232023110 37368031
     [Google Scholar]
  66. Pascual-FigalD.A. ZamoranoJ.L. DomingoM. Impact of dapagliflozin on cardiac remodelling in patients with chronic heart failure: The DAPA‐MODA study.Eur. J. Heart Fail.20232581352136010.1002/ejhf.2884 37211950
     [Google Scholar]
  67. XanthopoulosA. KatsiadasN. SkoularigkisS. Association between dapagliflozin, cardiac biomarkers and cardiac remodeling in patients with diabetes mellitus and heart failure.Life2023138177810.3390/life13081778 37629635
     [Google Scholar]
  68. ArabH.H. SafarM.M. ShahinN.N. Targeting ROS-dependent AKT/GSK-3β/NF-κB and DJ-1/Nrf2 pathways by dapagliflozin attenuates neuronal injury and motor dysfunction in rotenone-induced Parkinson’s disease rat model.ACS Chem. Neurosci.202112468970310.1021/acschemneuro.0c00722 33543924
     [Google Scholar]
  69. ChangY.K. ChoiH. JeongJ.Y. Dapagliflozin, SGLT2 inhibitor, attenuates renal ischemia-reperfusion injury.PLoS One2016117e015881010.1371/journal.pone.0158810 27391020
     [Google Scholar]
  70. JangJ. LeeT.J. SungE.G. SongI.H. KimJ.Y. Dapagliflozin induces apoptosis by downregulating cFILPL and increasing cFILPS instability in Caki 1 cells.Oncol. Lett.202224540110.3892/ol.2022.13521 36276495
     [Google Scholar]
  71. HuangX. GuoX. YanG. Dapagliflozin attenuates contrast-induced acute kidney injury by regulating the HIF-1α/HE4/NF-κB pathway.J. Cardiovasc. Pharmacol.202279690491310.1097/FJC.0000000000001268 35383661
     [Google Scholar]
  72. HuY. XuQ. LiH. Dapagliflozin reduces apoptosis of diabetic retina and human retinal microvascular endothelial cells through ERK1/2/cPLA2/AA/ROS pathway independent of hypoglycemic.Front. Pharmacol.20221382789610.3389/fphar.2022.827896 35281932
     [Google Scholar]
/content/journals/crcep/10.2174/0127724328313815240723044625
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The Effect of Dapagliflozin on Heart Function in Animal Models of Cardiac Ischemia, A Systematic Review and Meta-analysis
Curr Rev Clin Exper Pharm 20, 72 (2025); https://doi.org/10.2174/0127724328313815240723044625
/content/journals/crcep/10.2174/0127724328313815240723044625
/content/journals/crcep/10.2174/0127724328313815240723044625
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  • Article Type:     Research Article
Keyword(s): animal models; DAPA; dapagliflozin; echocardiographic parameters; Ischemic heart disease; meta-analysis

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