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Therapeutic Strategies Targeting Mitochondrial Dysfunction in Sepsis-induced Cardiomyopathy

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Abstract

Sepsis is an increasingly worldwide problem; it is currently regarded as a complex life-threatening dysfunction of one or more organs as a result of dysregulated host immune response to infections. The heart is one of the most affected organs, as roughly 10% to 70% of sepsis cases are estimated to turn into sepsis-induced cardiomyopathy (SIC). SIC can be defined as a reversible myocardial dysfunction characterized by dilated ventricles, impaired contractility, and decreased ejection fraction. Mitochondria play a critical role in the normal functioning of cardiac tissues as the heart is highly dependent on its production of adenosine triphosphate (ATP), its damage during SIC includes morphology impairment, mitophagy, biogenesis disequilibrium, electron transport chain disturbance, molecular damage from the actions of pro-inflammatory cytokines and many other different impairments that are major contributing factors to the severity of SIC. Although mitochondria-targeted therapies usage is still inadequate in clinical settings, the preclinical study outcomes promise that the implementation of these therapies may effectively treat SIC. This review summarizes the different therapeutic strategies targeting mitochondria structure, quality, and quantity abnormalities for the treatment of SIC.

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Data Availability

The authors confirm that the data used to support the findings of this article are included within the article.

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Abbreviations

AIF:

Apoptosis-inducing factor

AMPKα:

Adenosine monophosphate-activated protein kinase α

ATP:

Adenosine triphosphate

BCL-2:

B cell lymphoma-2

BCL2-L-13:

BCL2-like-13

BNIP3:

BCL2/adenovirus E1B 19 kDa interacting protein 3

CASP1:

Caspase-1

CAT:

Catalase

cAMP:

Cyclic adenosine monophosphate

CLP:

Cecal ligation and puncture

CoQ10:

Coenzyme Q10

CORM-2:

CO-releasing molecules-2

cTnT:

Cardiac troponin

DAMPs:

Damage-associated molecular patterns

DCM:

Dilated cardiomyopathy

DRP:

Dynamin-related protein

eNOS:

Endothelial nitric oxide synthase

ERR:

Estrogen-related receptor

ETC:

Electron transport chain

FNDC5:

Fibronectin type III domain containing 5

FUNDC1:

FUN14 domain-containing protein 1

GSDMD:

Gasdermin D

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

GSH:

Glutathione

Gαq:

Gq protein alpha subunit

HF:

Heart failure

huMSCs:

Human umbilical cord mesenchymal stem cells

IL:

Interleukin

IHD:

Ischemic heart disease

iNOS:

Inducible nitric oxide synthase

IMM:

Inner mitochondria membrane

JNK-LATS2:

Jun N-terminal kinase-large tumor suppressor 2

LC3:

Light chain 3

LTCC:

L-type calcium channel

LPS:

Lipopolysaccharide

LVEF:

Left ventricular ejection fraction

LVFS:

Left ventricular fraction shortening

MAPK:

Mitogen-activated protein kinase

MitoQ:

Mitochondria-targeted ubiquinone

mPTP:

Mitochondrial permeability transition pore

MFF:

Mitochondrial fission factor

Mfn:

Mitofusin

mTOR:

Mammalian target of rapamycin

mtDNA:

Mitochondria DNA

MUL1:

Mitochondrial ubiquitin ligase 1

NAD:

Nicotinamide adenine dinucleotide

NADPH:

Nicotinamide adenine dinucleotide phosphate

NLRP3:

Nucleotide-binding domain leucine-rich repeat, pyrin domain–containing-3

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NOX2:

NADPH oxidase-2

NaHS:

Sodium hydrosulfide

NF-κB:

Nuclear factor kappa B

NRF:

Nuclear respiratory factor

OCR:

Oxygen consumption rate

OMM:

Outer mitochondria membrane

OPA1:

Optic atrophy protein 1

OXPHOS:

Oxidative phosphorylation

PDC:

Pyruvate dehydrogenase complex

PDK:

Pyruvate dehydrogenase kinase

PEG-SOD:

Polyethylene glycol-conjugated–superoxide dismutase

PGAM5:

Phosphoglycerate mutase family member 5

PHB:

Prohibitin

PINK1:

PTEN-induced putative protein kinase 1

PI3K:

Phosphatidylinositol 3-kinases

PGC-1α:

Peroxisome proliferator-activated receptor γ coactivator-1α

PPAR:

Peroxisome proliferated-activated receptor

PKA:

Protein kinase A

PKC:

Protein kinase C

PTEN:

Phosphatase and tensin homolog

ROS:

Reactive oxygen species

RyR:

Ryanodine receptor

SESN2:

Sestrin 2

SERCA:

Sarcoplasmic endoplasmic reticulum Ca2+-ATPase

SHP:

Small heterodimer partner

SIC:

Sepsis-induced cardiomyopathy

SIMD:

Sepsis-induced myocardial dysfunction

SIRT:

Sirtuin

SOD:

Superoxide dismutase

SUMO:

Small ubiquitin-like modifier

TCA:

Tricarboxylic acid

TLR7:

Toll-like receptor 7

TFAM:

Mitochondrial transcription factor A

TNF- α:

Tumor necrosis factor-α

UCP:

Uncoupling protein

References

  1. Wasyluk W, Nowicka-Stążka P, Zwolak A. Heart Metabolism in Sepsis-Induced Cardiomyopathy—Unusual Metabolic Dysfunction of the Heart. Int J Environ Res Public Health. 2021;18(14):7598.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Donnino MW, Andersen LW, Chase M, et al. Randomized, double-blind, placebo-controlled trial of thiamine as a metabolic resuscitator in septic shock: a pilot study. Crit Care Med. 2016;44(2):360.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Walley KR. Sepsis-induced myocardial dysfunction. Curr Opin Crit Care. 2018;24(4):292–9.

    Article  MathSciNet  PubMed  Google Scholar 

  5. Beesley SJ, Weber G, Sarge T, et al. Septic cardiomyopathy. Crit Care Med. 2018;46(4):625–34.

    Article  PubMed  Google Scholar 

  6. Rackow E, Kaufman B, Falk J, Astiz M, Weil M. Hemodynamic response to fluid repletion in patients with septic shock: evidence for early depression of cardiac performance. Circ Shock. 1987;22(1):11–22.

    CAS  PubMed  Google Scholar 

  7. Martin L, Derwall M, Al Zoubi S, et al. The septic heart: current understanding of molecular mechanisms and clinical implications. Chest. 2019;155(2):427–37.

    Article  PubMed  Google Scholar 

  8. Tsolaki V, Makris D, Mantzarlis K, Zakynthinos E. Sepsis-induced cardiomyopathy: oxidative implications in the initiation and resolution of the damage. Oxidative Medicine and Cellular Longevity. 2017;2017.

  9. Pan P, Wang X, Liu D. The potential mechanism of mitochondrial dysfunction in septic cardiomyopathy. J Int Med Res. 2018;46(6):2157–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jarczak D, Kluge S, Nierhaus A. Sepsis-Pathophysiology and Therapeutic Concepts. Front Med (Lausanne). 2021;8:628302.

    Article  PubMed  Google Scholar 

  11. Zang Q, Maass DL, Tsai SJ, Horton JW. Cardiac mitochondrial damage and inflammation responses in sepsis. Surg Infect. 2007;8(1):41–54.

    Article  Google Scholar 

  12. Hollenberg SM, Singer M. Pathophysiology of sepsis-induced cardiomyopathy. Nat Rev Cardiol. 2021;18(6):424–34.

    Article  PubMed  Google Scholar 

  13. Sato R, Kuriyama A, Takada T, Nasu M, Luthe SK. Prevalence and risk factors of sepsis-induced cardiomyopathy: A retrospective cohort study. Medicine (Baltimore). 2016;95(39):e5031.

    Article  CAS  PubMed  Google Scholar 

  14. Jeong HS, Lee TH, Bang CH, Kim JH, Hong SJ. Risk factors and outcomes of sepsis-induced myocardial dysfunction and stress-induced cardiomyopathy in sepsis or septic shock: A comparative retrospective study. Medicine (Baltimore). 2018;97(13):e0263.

    Article  CAS  PubMed  Google Scholar 

  15. L’Heureux M, Sternberg M, Brath L, Turlington J, Kashiouris MG. Sepsis-Induced Cardiomyopathy: a Comprehensive Review. Curr Cardiol Rep. 2020;22(5):35.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mekontso Dessap A, Razazi K, Brun-Buisson C, Deux J-F. Myocardial viability in human septic heart. Intensive Care Med. 2014;40(11):1746–8.

    Article  PubMed  Google Scholar 

  17. Charpentier J, Luyt C-E, Fulla Y, et al. Brain natriuretic peptide: A marker of myocardial dysfunction and prognosis during severe sepsis. Crit Care Med. 2004;32(3):660–5.

    Article  CAS  PubMed  Google Scholar 

  18. Mehta NJ, Khan IA, Gupta V, et al. Cardiac troponin I predicts myocardial dysfunction and adverse outcome in septic shock. Int J Cardiol. 2004;95(1):13–7.

    Article  PubMed  Google Scholar 

  19. Werdan K, Oelke A, Hettwer S, et al. Septic cardiomyopathy: hemodynamic quantification, occurrence, and prognostic implications. Clin Res Cardiol. 2011;100(8):661–8.

    Article  PubMed  Google Scholar 

  20. Sato R, Nasu M. A review of sepsis-induced cardiomyopathy. J Intensive Care. 2015;3(1):1–7.

    Article  Google Scholar 

  21. Zangrillo A, Putzu A, Monaco F, et al. Levosimendan reduces mortality in patients with severe sepsis and septic shock: a meta-analysis of randomized trials. J Crit Care. 2015;30(5):908–13.

    Article  CAS  PubMed  Google Scholar 

  22. Schlesinger JJ, Burger CF. Methylene Blue for Acute Septic Cardiomyopathy in a Burned Patient. J Burn Care Res. 2016;37(3):e287–91.

    Article  PubMed  Google Scholar 

  23. Fan Y, Jiang M, Gong D, Zou C. Efficacy and safety of low-molecular-weight heparin in patients with sepsis: a meta-analysis of randomized controlled trials. Sci Rep. 2016;6:25984.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  24. Krishnan K, Wassermann TB, Tednes P, Bonderski V, Rech MA. Beyond the bundle: Clinical controversies in the management of sepsis in emergency medicine patients. Am J Emerg Med. 2022;51:296–303.

    Article  PubMed  Google Scholar 

  25. Vogel DJ, Murray J, Czapran AZ, et al. Veno-arterio-venous ECMO for septic cardiomyopathy: a single-centre experience. Perfusion. 2018;33(1_suppl):57–64.

  26. Alvarez S, Vico T, Vanasco V. Cardiac dysfunction, mitochondrial architecture, energy production, and inflammatory pathways: Interrelated aspects in endotoxemia and sepsis. Int J Biochem Cell Biol. 2016;81:307–14.

    Article  CAS  PubMed  Google Scholar 

  27. Halestrap AP, McStay GP, Clarke SJ. The permeability transition pore complex: another view. Biochimie. 2002;84(2–3):153–66.

    Article  CAS  PubMed  Google Scholar 

  28. Bernardi P, Di Lisa F. The mitochondrial permeability transition pore: molecular nature and role as a target in cardioprotection. J Mol Cell Cardiol. 2015;78:100–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bernardi P, Krauskopf A, Basso E, et al. The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J. 2006;273(10):2077–99.

    Article  CAS  PubMed  Google Scholar 

  30. Kim I, Rodriguez-Enriquez S, Lemasters JJ. Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys. 2007;462(2):245–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Larche J, Lancel S, Hassoun SM, et al. Inhibition of mitochondrial permeability transition prevents sepsis-induced myocardial dysfunction and mortality. J Am Coll Cardiol. 2006;48(2):377–85.

    Article  CAS  PubMed  Google Scholar 

  32. Pan P, Zhang H, Su L, Wang X, Liu D. Melatonin balance the autophagy and apoptosis by regulating UCP2 in the LPS-induced cardiomyopathy. Molecules. 2018;23(3):675.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Fauvel H, Marchetti P, Obert G, et al. Protective effects of cyclosporin A from endotoxin-induced myocardial dysfunction and apoptosis in rats. Am J Respir Crit Care Med. 2002;165(4):449–55.

    Article  PubMed  Google Scholar 

  34. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84(1):277–359.

    Article  CAS  PubMed  Google Scholar 

  35. Hu Y, Yan JB, Zheng MZ, et al. Mitochondrial aldehyde dehydrogenase activity protects against lipopolysaccharide-induced cardiac dysfunction in rats. Mol Med Rep. 2015;11(2):1509–15.

    Article  CAS  PubMed  Google Scholar 

  36. MacGarvey NC, Suliman HB, Bartz RR, et al. Activation of mitochondrial biogenesis by heme oxygenase-1–mediated NF-E2–related factor-2 induction rescues mice from lethal Staphylococcus aureus sepsis. Am J Respir Crit Care Med. 2012;185(8):851–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Durand A, Duburcq T, Dekeyser T, et al. Involvement of mitochondrial disorders in septic cardiomyopathy. Oxidative medicine and cellular longevity. 2017;2017.

  38. Liang D, Huang A, Jin Y, et al. Protective effects of exogenous NaHS against sepsis-induced myocardial mitochondrial injury by enhancing the PGC-1α/NRF2 pathway and mitochondrial biosynthesis in mice. American J Transl Res. 2018;10(5):1422.

    CAS  Google Scholar 

  39. Rahmel T, Marko B, Nowak H, et al. Mitochondrial dysfunction in sepsis is associated with diminished intramitochondrial TFAM despite its increased cellular expression. Sci Rep. 2020;10(1):1–11.

    Article  ADS  Google Scholar 

  40. Carré JE, Orban J-C, Re L, et al. Survival in critical illness is associated with early activation of mitochondrial biogenesis. Am J Respir Crit Care Med. 2010;182(6):745–51.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Nagy G, Koncz A, Perl A. T cell activation-induced mitochondrial hyperpolarization is mediated by Ca2+-and redox-dependent production of nitric oxide. J Immunol. 2003;171(10):5188–97.

    Article  CAS  PubMed  Google Scholar 

  42. Suliman HB, Piantadosi CA. Mitochondrial quality control as a therapeutic target. Pharmacol Rev. 2016;68(1):20–48.

    Article  CAS  PubMed  Google Scholar 

  43. Lancel S, Hassoun SM, Favory R, et al. Carbon monoxide rescues mice from lethal sepsis by supporting mitochondrial energetic metabolism and activating mitochondrial biogenesis. J Pharmacol Exp Ther. 2009;329(2):641–8.

    Article  CAS  PubMed  Google Scholar 

  44. Wang X, Qin W, Qiu X, et al. A novel role of exogenous carbon monoxide on protecting cardiac function and improving survival against sepsis via mitochondrial energetic metabolism pathway. Int J Biol Sci. 2014;10(7):777.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Suliman HB, Carraway MS, Tatro LG, Piantadosi CA. A new activating role for CO in cardiac mitochondrial biogenesis. J Cell Sci. 2007;120(2):299–308.

    Article  CAS  PubMed  Google Scholar 

  46. Mattingly KA, Ivanova MM, Riggs KA, et al. Estradiol stimulates transcription of nuclear respiratory factor-1 and increases mitochondrial biogenesis. Mol Endocrinol. 2008;22(3):609–22.

    Article  CAS  PubMed  Google Scholar 

  47. Li Y, Feng Y-F, Liu X-T, et al. Songorine promotes cardiac mitochondrial biogenesis via Nrf2 induction during sepsis. Redox Biol. 2021;38:101771.

    Article  CAS  PubMed  Google Scholar 

  48. Hondares E, Pineda-Torra I, Iglesias R, et al. PPARδ, but not PPARα, activates PGC-1α gene transcription in muscle. Biochem Biophys Res Commun. 2007;354(4):1021–7.

    Article  CAS  PubMed  Google Scholar 

  49. Yang Y, Zhu Y, Xiao J, et al. Maresin conjugates in tissue regeneration 1 prevents lipopolysaccharide-induced cardiac dysfunction through improvement of mitochondrial biogenesis and function. Biochem Pharmacol. 2020;177:114005.

    Article  CAS  PubMed  Google Scholar 

  50. Sánchez-Villamil JP, D’Annunzio V, Finocchietto P, et al. Cardiac-specific overexpression of thioredoxin 1 attenuates mitochondrial and myocardial dysfunction in septic mice. Int J Biochem Cell Biol. 2016;81:323–34.

    Article  PubMed  Google Scholar 

  51. Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell. 2006;127(6):1109–22.

    Article  CAS  PubMed  Google Scholar 

  52. Xin T, Lu C. SirT3 activates AMPK-related mitochondrial biogenesis and ameliorates sepsis-induced myocardial injury. Aging (Albany NY). 2020;12(16):16224.

    Article  CAS  PubMed  Google Scholar 

  53. Russell LK, Mansfield CM, Lehman JJ, et al. Cardiac-specific induction of the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental stage-dependent manner. Circ Res. 2004;94(4):525–33.

    Article  CAS  PubMed  Google Scholar 

  54. Stanzani G, Duchen MR, Singer M. The role of mitochondria in sepsis-induced cardiomyopathy. Biochimica et Biophysica Acta (BBA)- Molecular Basis of Disease. 2019;1865(4):759–73.

    Article  CAS  PubMed  Google Scholar 

  55. Ni H-M, Williams JA, Ding W-X. Mitochondrial dynamics and mitochondrial quality control. Redox Biol. 2015;4:6–13.

    Article  CAS  PubMed  Google Scholar 

  56. Marín-García J, Akhmedov AT. Mitochondrial dynamics and cell death in heart failure. Heart Fail Rev. 2016;21(2):123–36.

    Article  PubMed  Google Scholar 

  57. Jin J-Y, Wei X-X, Zhi X-L, Wang X-H, Meng D. Drp1-dependent mitochondrial fission in cardiovascular disease. Acta Pharmacologica Sinica. 2021;42(5):655–64.

    Article  CAS  PubMed  Google Scholar 

  58. Ishihara T, Ban-Ishihara R, Maeda M, et al. Dynamics of mitochondrial DNA nucleoids regulated by mitochondrial fission is essential for maintenance of homogeneously active mitochondria during neonatal heart development. Mol Cell Biol. 2015;35(1):211–23.

    Article  PubMed  Google Scholar 

  59. Chen H, Ren S, Clish C, et al. Titration of mitochondrial fusion rescues Mff-deficient cardiomyopathy. J Cell Biol. 2015;211(4):795–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Disatnik MH, Ferreira JC, Campos JC, et al. Acute inhibition of excessive mitochondrial fission after myocardial infarction prevents long-term cardiac dysfunction. J Am Heart Assoc. 2013;2(5):e000461.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Zhou H, Zhang Y, Hu S, et al. Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC 1-HK 2-mPTP-mitophagy axis. J Pineal Res. 2017;63(1):e12413.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Hernandez-Resendiz S, Prunier F, Girao H, et al. Targeting mitochondrial fusion and fission proteins for cardioprotection. J Cell Mol Med. 2020;24(12):6571–85.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Zang QS, Sadek H, Maass DL, et al. Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model. American J Physiol-Heart Circ Physiol. 2012;302(9):H1847–59.

    Article  CAS  Google Scholar 

  64. Wu Y, Yao Y-M, Lu Z-Q. Mitochondrial quality control mechanisms as potential therapeutic targets in sepsis-induced multiple organ failure. J Mol Med. 2019;97(4):451–62.

    Article  CAS  PubMed  Google Scholar 

  65. Gonzalez AS, Elguero ME, Finocchietto P, et al. Abnormal mitochondrial fusion–fission balance contributes to the progression of experimental sepsis. Free Radical Res. 2014;48(7):769–83.

    Article  CAS  Google Scholar 

  66. Gao D, Zhang L, Dhillon R, et al. Dynasore protects mitochondria and improves cardiac lusitropy in Langendorff perfused mouse heart. PLoS ONE. 2013;8(4):e60967.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  67. Wu D, Dasgupta A, Chen KH, et al. Identification of novel dynamin-related protein 1 (Drp1) GTPase inhibitors: Therapeutic potential of Drpitor1 and Drpitor1a in cancer and cardiac ischemia-reperfusion injury. FASEB J. 2020;34(1):1447–64.

    Article  CAS  PubMed  Google Scholar 

  68. Tan Y, Ouyang H, Xiao X, Zhong J, Dong M. Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway. Cell Stress Chaperones. 2019;24(3):595–608.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Yu W, Mei X, Zhang Q, et al. Yap overexpression attenuates septic cardiomyopathy by inhibiting DRP1-related mitochondrial fission and activating the ERK signaling pathway. J Recept Signal Transduct Res. 2019;39(2):175–86.

    Article  CAS  PubMed  Google Scholar 

  70. Pride CK, Mo L, Quesnelle K, et al. Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion. Cardiovasc Res. 2014;101(1):57–68.

    Article  CAS  Google Scholar 

  71. Bian X, Xu J, Zhao H, et al. Zinc-induced SUMOylation of dynamin-related protein 1 protects the heart against ischemia-reperfusion injury. Oxidative medicine and cellular longevity. 2019;2019.

  72. Ikeda Y, Shirakabe A, Maejima Y, et al. Endogenous Drp1 mediates mitochondrial autophagy and protects the heart against energy stress. Circ Res. 2015;116(2):264–78.

    Article  CAS  PubMed  Google Scholar 

  73. Wang J, Zhou H. Mitochondrial quality control mechanisms as molecular targets in cardiac ischemia–reperfusion injury. Acta Pharmaceutica Sinica B. 2020;10(10):1866–79.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Song Z, Ghochani M, McCaffery JM, Frey TG, Chan DC. Mitofusins and OPA1 mediate sequential steps in mitochondrial membrane fusion. Mol Biol Cell. 2009;20(15):3525–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Ferreira JCB, Campos JC, Qvit N, et al. A selective inhibitor of mitofusin 1-βIIPKC association improves heart failure outcome in rats. Nat Commun. 2019;10(1):329.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  76. Chen Y, Dorn GW 2nd. PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science. 2013;340(6131):471–5.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  77. Burke N, Hall AR, Hausenloy DJ. OPA1 in Cardiovascular Health and Disease. Curr Drug Targets. 2015;16(8):912–20.

    Article  CAS  PubMed  Google Scholar 

  78. Huang J, Li R, Wang C. The Role of Mitochondrial Quality Control in Cardiac Ischemia/Reperfusion Injury. Oxidative Med Cellular Longevity. 2021;2021.

  79. Neuspiel M, Zunino R, Gangaraju S, Rippstein P, McBride H. Activated mitofusin 2 signals mitochondrial fusion, interferes with Bax activation, and reduces susceptibility to radical induced depolarization. J Biol Chem. 2005;280(26):25060–70.

    Article  CAS  PubMed  Google Scholar 

  80. Papanicolaou KN, Khairallah RJ, Ngoh GA, et al. Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes. Mol Cell Biol. 2011;31(6):1309–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Dorn GW, Clark CF, Eschenbacher WH, et al. MARF and Opa1 control mitochondrial and cardiac function in Drosophila. Circ Res. 2011;108(1):12–7.

    Article  CAS  PubMed  Google Scholar 

  82. Chen L, Liu T, Tran A, et al. OPA 1 Mutation and Late-Onset Cardiomyopathy: Mitochondrial Dysfunction and mtDNA Instability. J Am Heart Assoc. 2012;1(5):e003012.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Merkwirth C, Dargazanli S, Tatsuta T, et al. Prohibitins control cell proliferation and apoptosis by regulating OPA1-dependent cristae morphogenesis in mitochondria. Genes Dev. 2008;22(4):476–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Zhang Y, Wang Y, Xu J, et al. Melatonin attenuates myocardial ischemia-reperfusion injury via improving mitochondrial fusion/mitophagy and activating the AMPK-OPA1 signaling pathways. J Pineal Res. 2019;66(2):e12542.

    Article  PubMed  Google Scholar 

  85. Maneechote C, Palee S, Kerdphoo S, et al. Balancing mitochondrial dynamics via increasing mitochondrial fusion attenuates infarct size and left ventricular dysfunction in rats with cardiac ischemia/reperfusion injury. Clin Sci. 2019;133(3):497–513.

    Article  CAS  Google Scholar 

  86. Shen T, Zheng M, Cao C, et al. Mitofusin-2 is a major determinant of oxidative stress-mediated heart muscle cell apoptosis. J Biol Chem. 2007;282(32):23354–61.

    Article  CAS  PubMed  Google Scholar 

  87. Ong S-B, Subrayan S, Lim SY, et al. Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation. 2010;121(18):2012–22.

    Article  CAS  PubMed  Google Scholar 

  88. Boyman L, Karbowski M, Lederer WJ. Regulation of Mitochondrial ATP Production: Ca2+ Signaling and Quality Control. Trends Mol Med. 2020;26(1):21–39.

    Article  CAS  PubMed  Google Scholar 

  89. Brealey D, Singer M. Mitochondrial dysfunction in sepsis. Current Infectious Disease Rep. 2003;5(5):365–71.

    Article  Google Scholar 

  90. Leite HP, de Lima LFP. Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic? J Thorac Dis. 2016;8(7):E552.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Giacalone M, Martinelli R, Abramo A, et al. Rapid reversal of severe lactic acidosis after thiamine administration in critically ill adults: a report of 3 cases. Nutr Clin Pract. 2015;30(1):104–10.

    Article  PubMed  Google Scholar 

  92. Escames G, López LC, Ortiz F, et al. Attenuation of cardiac mitochondrial dysfunction by melatonin in septic mice. FEBS J. 2007;274(8):2135–47.

    Article  CAS  PubMed  Google Scholar 

  93. Galley HF, Lowes DA, Allen L, et al. Melatonin as a potential therapy for sepsis: a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis. J Pineal Res. 2014;56(4):427–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. McCall CE, Zabalawi M, Liu T, et al. Pyruvate dehydrogenase complex stimulation promotes immunometabolic homeostasis and sepsis survival. JCI insight. 2018;3:15.

    Article  Google Scholar 

  95. Stacpoole PW, Wright EC, Baumgartner TG, et al. A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. N Engl J Med. 1992;327(22):1564–9.

    Article  CAS  PubMed  Google Scholar 

  96. Eyenga P, Roussel D, Rey B, et al. Mechanical ventilation preserves diaphragm mitochondrial function in a rat sepsis model. Intensive Care Med Exp. 2021;9(1):19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Geng N, Ren L, Xu L, Zou D, Pang W. Clinical outcomes of nicorandil administration in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials. BMC Cardiovasc Disord. 2021;21(1):488.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Bank HV, Hurtado-Thiele M, Oshimura N, Simcox J. Mitochondrial Lipid Signaling and Adaptive Thermogenesis. Metabolites. 2021;11(2):124.

    Article  Google Scholar 

  99. Xie C, Zhang Y, Tran TD, et al. Irisin controls growth, intracellular Ca2+ signals, and mitochondrial thermogenesis in cardiomyoblasts. PLoS ONE. 2015;10(8):e0136816.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Kong X, Wang R, Xue Y, et al. Sirtuin 3, a new target of PGC-1α, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS ONE. 2010;5(7):e11707.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  101. Demine S, Renard P, Arnould T. Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases. Cells. 2019;8(8):795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Tian XY, Ma S, Tse G, Wong WT, Huang Y. Uncoupling protein 2 in cardiovascular health and disease. Front Physiol. 2018;9:1060.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Chen Huang J-D, Lyu S-L, Liu J-J, Zeng C, Q-Y. Correlation between uncoupling protein 2 expression and myocardial mitochondrial injury in rats with sepsis induced by lipopolysaccharide Zhongguo dang dai er ke za zhi. Chinese J Contemporary Pediatr. 2016;18(2):159–64.

    Google Scholar 

  104. Huang J, Peng W, Zheng Y, et al. Upregulation of UCP2 expression protects against LPS-induced oxidative stress and apoptosis in cardiomyocytes. Oxidative medicine and cellular longevity. 2019;2019.

  105. Zheng G, Lyu J, Liu S, et al. Silencing of uncoupling protein 2 by small interfering RNA aggravates mitochondrial dysfunction in cardiomyocytes under septic conditions. Int J Mol Med. 2015;35(6):1525–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Chen Y, Chen G, Zhang J, et al. Uncoupling protein 2 facilitates insulin-elicited protection against lipopolysaccharide-induced myocardial dysfunction. Mater Express. 2020;10(3):337–49.

    Article  CAS  Google Scholar 

  107. Kovacic P, Pozos RS, Somanathan R, Shangari N, O’Brien PJ. Mechanism of mitochondrial uncouplers, inhibitors, and toxins: focus on electron transfer, free radicals, and structure-activity relationships. Curr Med Chem. 2005;12(22):2601–23.

    Article  CAS  PubMed  Google Scholar 

  108. Supale S, Li N, Brun T, Maechler P. Mitochondrial dysfunction in pancreatic β cells. Trends Endocrinol Metab. 2012;23(9):477–87.

    Article  CAS  PubMed  Google Scholar 

  109. Ray PD, Huang B-W, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012;24(5):981–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Ganten D, Ruckpaul K. Encyclopedic reference of genomics and proteomics in molecular medicine. Springer; 2006.

  111. Kumar S, Gupta E, Srivastava VK, et al. Nitrosative stress and cytokines are linked with the severity of sepsis and organ dysfunction. Br J Biomed Sci. 2019;76(1):29–34.

    Article  CAS  PubMed  Google Scholar 

  112. MatÉs JM, Pérez-Gómez C, De Castro IN. Antioxidant enzymes and human diseases. Clin Biochem. 1999;32(8):595–603.

    Article  PubMed  Google Scholar 

  113. Supinski GS, Callahan LA. Polyethylene glycol–superoxide dismutase prevents endotoxin-induced cardiac dysfunction. Am J Respir Crit Care Med. 2006;173(11):1240–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Liu Y, Yang W, Sun X, et al. SS31 ameliorates sepsis-induced heart injury by inhibiting oxidative stress and inflammation. Inflammation. 2019;42(6):2170–80.

    Article  CAS  PubMed  Google Scholar 

  115. Wang Z, Bu L, Yang P, Feng S, Xu F. Alleviation of sepsis-induced cardiac dysfunction by overexpression of Sestrin2 is associated with inhibition of p-S6K and activation of the p-AMPK pathway. Mol Med Rep. 2019;20(3):2511–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Budanov AV, Sablina AA, Feinstein E, Koonin EV, Chumakov PM. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science. 2004;304(5670):596–600.

    Article  ADS  CAS  PubMed  Google Scholar 

  117. Abitagaoglu S, Akinci S, Saricaoglu F, et al. Effect of Coenzyme Q10 on Organ Damage in Sepsis. Bratisl Lek Listy. 2015;116(7):433–9.

    CAS  PubMed  Google Scholar 

  118. Soltani R, Alikiaie B, Shafiee F, Amiri H, Mousavi S. Coenzyme Q10 improves the survival and reduces inflammatory markers in septic patients. Bratisl Lek Listy. 2020;121(2):154–8.

    CAS  PubMed  Google Scholar 

  119. Lowes DA, Thottakam BM, Webster NR, Murphy MP, Galley HF. The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide-peptidoglycan model of sepsis. Free Radic Biol Med. 2008;45(11):1559–65.

    Article  CAS  PubMed  Google Scholar 

  120. Kokkinaki D, Hoffman M, Kalliora C, et al. Chemically synthesized Secoisolariciresinol diglucoside (LGM2605) improves mitochondrial function in cardiac myocytes and alleviates septic cardiomyopathy. J Mol Cell Cardiol. 2019;127:232–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Mattox TA, Psaltis C, Weihbrecht K, et al. Prohibitin-1 Is a Dynamically Regulated Blood Protein With Cardioprotective Effects in Sepsis. J Am Heart Assoc. 2021;10(14):e019877.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Lee M-T, Jung S-Y, Baek MS, Shin J, Kim W-Y. Early Vitamin C, Hydrocortisone, and Thiamine Treatment for Septic Cardiomyopathy: A Propensity Score Analysis. J Personalized Med. 2021;11(7):610.

    Article  Google Scholar 

  123. Hobai IA, Edgecomb J, LaBarge K, Colucci WS. Dysregulation of intracellular calcium transporters in animal models of sepsis induced cardiomyopathy. Shock (Augusta, Ga). 2015;43(1):3.

    Article  CAS  PubMed  Google Scholar 

  124. Hassoun SM, Marechal X, Montaigne D, et al. Prevention of endotoxin-induced sarcoplasmic reticulum calcium leak improves mitochondrial and myocardial dysfunction. Crit Care Med. 2008;36(9):2590–6.

    Article  CAS  PubMed  Google Scholar 

  125. Joseph LC, Kokkinaki D, Valenti M-C, et al. Inhibition of NADPH oxidase 2 (NOX2) prevents sepsis-induced cardiomyopathy by improving calcium handling and mitochondrial function. JCI insight. 2017;2:17.

    Article  Google Scholar 

  126. Zhou Q, Xie M, Zhu J, et al. PINK1 Contained in huMSCs-Exosomes Prevents Cardiomyocyte Mitochondrial Calcium Overload in Sepsis by Recovering Mitochondrial Ca2+ Efflux. 2020.

  127. Wang L, Wei Y. The Improvements of Cardiac Calcium Handing and Cardiomyopathy in Septic Rats via Nos Signaling by Neuregulin-1. Circulation. 2018;138(Suppl_1):A11603-A.

    Google Scholar 

  128. Wiewel MA, Van Vught LA, Scicluna BP, et al. Prior use of calcium channel blockers is associated with decreased mortality in critically ill patients with sepsis: a prospective observational study. Crit Care Med. 2017;45(3):454–63.

    Article  CAS  PubMed  Google Scholar 

  129. Shang X, Lin K, Yu R, et al. Resveratrol Protects the Myocardium in Sepsis by Activating the Phosphatidylinositol 3-Kinases (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway and Inhibiting the Nuclear Factor-κB (NF-κB) Signaling Pathway. Med Sci Monit. 2019;25:9290–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Smeding L, Leong-Poi H, Hu P, et al. Salutary effect of resveratrol on sepsis-induced myocardial depression. Crit Care Med. 2012;40(6):1896–907.

    Article  CAS  PubMed  Google Scholar 

  131. Harrington JS, Choi AMK, Nakahira K. Mitochondrial DNA in Sepsis. Curr Opin Crit Care. 2017;23(4):284–90.

    Article  PubMed  PubMed Central  Google Scholar 

  132. West AP, Khoury-Hanold W, Staron M, et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature. 2015;520(7548):553–7.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  133. Kung CT, Hsiao SY, Tsai TC, et al. Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room. J Transl Med. 2012;10:130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Jung SS, Moon JS, Xu JF, et al. Carbon monoxide negatively regulates NLRP3 inflammasome activation in macrophages. Am J Physiol Lung Cell Mol Physiol. 2015;308(10):L1058–67.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2011;12(1):9–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Oka T, Hikoso S, Yamaguchi O, et al. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature. 2012;485(7397):251–5.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  137. Yao X, Carlson D, Sun Y, et al. Mitochondrial ROS Induces Cardiac Inflammation via a Pathway through mtDNA Damage in a Pneumonia-Related Sepsis Model. PLoS ONE. 2015;10(10):e0139416.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Bonekamp NA, Larsson NG. SnapShot Mitochondrial Nucleoid. Cell. 2018;172(1–2):388-e1.

    Article  CAS  PubMed  Google Scholar 

  139. Yin X, Xin H, Mao S, Wu G, Guo L. The role of autophagy in sepsis: protection and injury to organs. Front Physiol. 2019;10:1071.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Queliconi BB, Kowaltowski AJ, Gottlieb RA. Bicarbonate increases ischemia-reperfusion damage by inhibiting mitophagy. PLoS ONE. 2016;11(12):e0167678.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Lu W, Sun J, Yoon JS, et al. Mitochondrial protein PGAM5 regulates mitophagic protection against cell necroptosis. PLoS ONE. 2016;11(1):e0147792.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Hertz NT, Berthet A, Sos ML, et al. A neo-substrate that amplifies catalytic activity of parkinson’s-disease-related kinase PINK1. Cell. 2013;154(4):737–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Green DR, Van Houten B. Mitochondrial quality control. Cell. 2011;147(4):950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Geisler S, Holmström KM, Skujat D, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010;12(2):119–31.

    Article  CAS  PubMed  Google Scholar 

  145. Ordureau A, Sarraf SA, Duda DM, et al. Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol Cell. 2014;56(3):360–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Sedlackova L, Korolchuk VI. Mitochondrial quality control as a key determinant of cell survival. Biochimica et Biophysica Acta (BBA)-Molecular Cell Res. 2019;1866(4):575–87.

    Article  CAS  Google Scholar 

  147. Wei Y, Chiang WC, Sumpter R, et al. Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor. Cell. 2017;168(1–2):224-38.e10.

    Article  CAS  PubMed  Google Scholar 

  148. Yun J, Puri R, Yang H, et al. MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin. Elife. 2014;3:e01958.

    Article  PubMed  PubMed Central  Google Scholar 

  149. Cadete VJ, Vasam G, Menzies KJ, Burelle Y. 2019 Mitochondrial quality control in the cardiac system An integrative view. Biochimica et Biophysica Acta (BBA)-Molecular Basis Disease. 1865;4:782–96.

    Google Scholar 

  150. Liu L, Feng D, Chen G, et al. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol. 2012;14(2):177–85.

    Article  PubMed  Google Scholar 

  151. Yoo S-M, Jung Y-K. A molecular approach to mitophagy and mitochondrial dynamics. Mol Cells. 2018;41(1):18.

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Zhang J, Ney PA. Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ. 2009;16(7):939–46.

    Article  CAS  PubMed  Google Scholar 

  153. Murakawa T, Yamaguchi O, Hashimoto A, et al. Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation. Nat Commun. 2015;6:7527.

    Article  ADS  PubMed  Google Scholar 

  154. Chu CT, Ji J, Dagda RK, et al. Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat Cell Biol. 2013;15(10):1197–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Zhang E, Zhao X, Zhang L, et al. Minocycline promotes cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy to prevent sepsis-induced cardiac dysfunction by Akt/mTOR signaling. Apoptosis. 2019;24(3):369–81.

    Article  CAS  PubMed  Google Scholar 

  156. Cao Y, Han X, Pan H, et al. Emerging protective roles of shengmai injection in septic cardiomyopathy in mice by inducing myocardial mitochondrial autophagy via caspase-3/Beclin-1 axis. Inflamm Res. 2020;69(1):41–50.

    Article  CAS  PubMed  Google Scholar 

  157. Andres AM, Hernandez G, Lee P, et al. Mitophagy is required for acute cardioprotection by simvastatin. Antioxid Redox Signal. 2014;21(14):1960–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Wang S, Zhao Z, Feng X, et al. Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition. J Cell Mol Med. 2018;22(10):5132–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Hsieh C-H, Pai P-Y, Hsueh H-W, Yuan S-S, Hsieh Y-C. Complete induction of autophagy is essential for cardioprotection in sepsis. Ann Surg. 2011;253(6):1190–200.

    Article  PubMed  Google Scholar 

  160. Jiang X, Cai S, Jin Y, et al. Irisin Attenuates Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in the H9C2 Cellular Model of Septic Cardiomyopathy through Augmenting Fundc1-Dependent Mitophagy. Oxidative Medicine and Cellular Longevity. 2021;2021.

  161. Bian X, Teng T, Zhao H, et al. Zinc prevents mitochondrial superoxide generation by inducing mitophagy in the setting of hypoxia/reoxygenation in cardiac cells. Free Radical Res. 2018;52(1):80–91.

    Article  CAS  Google Scholar 

  162. Jang S-y, Kang HT, Hwang ES. Nicotinamide-induced mitophagy: event mediated by high NAD+/NADH ratio and SIRT1 protein activation. J Biological Chemistry. 2012;287(23):19304–14.

    Article  CAS  Google Scholar 

  163. Ji W, Wan T, Zhang F, et al. Aldehyde Dehydrogenase 2 Protects Against Lipopolysaccharide-Induced Myocardial Injury by Suppressing Mitophagy. Front Pharmacol. 2021;12:1025.

    Article  Google Scholar 

  164. Roshanravan B, Liu SZ, Ali AS, et al. In vivo mitochondrial ATP production is improved in older adult skeletal muscle after a single dose of elamipretide in a randomized trial. PLoS ONE. 2021;16(7):e0253849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Hortmann M, Robinson S, Mohr M, et al. The mitochondria-targeting peptide elamipretide diminishes circulating HtrA2 in ST-segment elevation myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2019;8(8):695–702.

    Article  PubMed  Google Scholar 

  166. Daubert MA, Yow E, Dunn G, et al. Novel mitochondria-targeting peptide in heart failure treatment a randomized, placebo-controlled trial of elamipretide. Circ Heart Failure. 2017;10(12):e004389.

    Article  CAS  PubMed  Google Scholar 

  167. Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358(9):877–87.

    Article  CAS  PubMed  Google Scholar 

  168. Patel BM, Chittock DR, Russell JA, Walley KR. Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology. 2002;96(3):576–82.

    Article  CAS  PubMed  Google Scholar 

  169. Morelli A, Ertmer C, Westphal M, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2013;310(16):1683–91.

    Article  PubMed  Google Scholar 

  170. Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest. 2017;151(6):1229–38.

    Article  PubMed  Google Scholar 

  171. Antcliffe DB, Santhakumaran S, Orme RML, et al. Levosimendan in septic shock in patients with biochemical evidence of cardiac dysfunction: a subgroup analysis of the LeoPARDS randomised trial. Intensive Care Med. 2019;45(10):1392–400.

    Article  CAS  PubMed  Google Scholar 

  172. Kim WY, Baek MS, Kim YS, et al. Glucose-insulin-potassium correlates with hemodynamic improvement in patients with septic myocardial dysfunction. J Thorac Dis. 2016;8(12):3648–57.

    Article  PubMed  PubMed Central  Google Scholar 

  173. Hernandez G, Bruhn A, Luengo C, et al. Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebo-controlled, double-blind, crossover study. Intensive Care Med. 2013;39(8):1435–43.

    Article  CAS  PubMed  Google Scholar 

  174. Kopterides P, Falagas M. Statins for sepsis: a critical and updated review. Clin Microbiol Infect. 2009;15(4):325–34.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the National Natural Sciences Foundation of China (No. 81770490), the Planned Science and Technology Project of Hunan Province, China (No.2020JJ4535), and the Key Laboratory for Arteriosclerology of Hunan Province (Basic Medicine Sciences in University of South China).

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  1. International College, University of South China, 28, W Changsheng Road, Hengyang, 421001, Hunan, China

    Oluwabukunmi Modupe Salami & Olive Habimana

  2. Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hengyang Medical School, University of South China, 28, W Changsheng Road, Hengyang, 421001, Hunan, China

    Jin-fu Peng & Guang-Hui Yi

  3. Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, 28, W Changsheng Road, Hengyang, 421001, Hunan, China

    Jin-fu Peng & Guang-Hui Yi

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  1. Oluwabukunmi Modupe Salami
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  4. Guang-Hui Yi
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All authors contributed to the manuscript’s conception and design. Material preparation, literature collection, and analysis were performed by Salami Oluwabukunmi Modupe, Habimana Olive, and Jinfu Peng. Guang-hui Yi gave the outline of the manuscript and continually gave intellectual suggestions for the article.

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Salami, O.M., Habimana, O., Peng, Jf. et al. Therapeutic Strategies Targeting Mitochondrial Dysfunction in Sepsis-induced Cardiomyopathy. Cardiovasc Drugs Ther 38, 163–180 (2024). https://doi.org/10.1007/s10557-022-07354-8

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