Insight into Cardioprotective Effects and Mechanisms of Dexmedetomidine.
Cardioprotective
Cell death
Dexmedetomidine
Myocardial ischemia-reperfusion injury
α2 adrenoreceptor agonist
Journal
Cardiovascular drugs and therapy
ISSN: 1573-7241
Titre abrégé: Cardiovasc Drugs Ther
Pays: United States
ID NLM: 8712220
Informations de publication
Date de publication:
13 Jun 2024
13 Jun 2024
Historique:
accepted:
17
05
2024
medline:
13
6
2024
pubmed:
13
6
2024
entrez:
13
6
2024
Statut:
aheadofprint
Résumé
Cardiovascular disease remains the leading cause of death worldwide. Dexmedetomidine is a highly selective α2 adrenergic receptor agonist with sedative, analgesic, anxiolytic, and sympatholytic properties, and several studies have shown its possible protective effects in cardiac injury. The aim of this review is to further elucidate the underlying cardioprotective mechanisms of dexmedetomidine, thus suggesting its potential in the clinical management of cardiac injury. Our review summarizes the findings related to the involvement of dexmedetomidine in cardiac injury and discusses the results in the light of different mechanisms. We found that numerous mechanisms may contribute to the cardioprotective effects of dexmedetomidine, including the regulation of programmed cell death, autophagy and fibrosis, alleviation of inflammatory response, endothelial dysfunction and microcirculatory derangements, improvement of mitochondrial dysregulation, hemodynamics, and arrhythmias. Dexmedetomidine may play a promising and beneficial role in the treatment of cardiovascular disease.
Identifiants
pubmed: 38869744
doi: 10.1007/s10557-024-07579-9
pii: 10.1007/s10557-024-07579-9
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : the National Natural Science Foundation of China
ID : 82060060
Organisme : Joint Special Key Fund of Applied Fundamental Research of Kunming Medical University granted by Science and Technology Office of Yunnan
ID : 202201AY070001-040
Organisme : Yunnan Health Training Project of High Levels Talents
ID : L-2018007
Organisme : Yunnan Provincial Ten Thousand-Talent Program-Famous Doctor
ID : YNWR-MY-2018-043
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Li Z, Lin L, Wu H, et al. Global, Regional, and National Death, and Disability-Adjusted Life-Years (DALYs) for cardiovascular disease in 2017 and trends and risk analysis from 1990 to 2017 using the Global Burden of Disease Study and implications for prevention. Front Public Health. 2021;9:559751. https://doi.org/10.3389/fpubh.2021.559751 .
doi: 10.3389/fpubh.2021.559751
pubmed: 34778156
pmcid: 8589040
Afonso J, Reis F. Dexmedetomidine: current role in anesthesia and intensive care. Rev Bras Anestesiol. 2012;62(1):118–33. https://doi.org/10.1016/S0034-7094(12)70110-1 .
doi: 10.1016/S0034-7094(12)70110-1
pubmed: 22248773
Brock L. Dexmedetomidine in adult patients in cardiac surgery critical care: an evidence-based review. AACN Adv Crit Care. 2019;30(3):259–68. https://doi.org/10.4037/aacnacc2019888 .
doi: 10.4037/aacnacc2019888
pubmed: 31462522
Vandemoortele O, Hannivoort LN, Vanhoorebeeck F, Struys M, Vereecke HEM. General purpose pharmacokinetic-pharmacodynamic models for target-controlled infusion of anaesthetic drugs: a narrative review. J Clin Med. 2022;11(9). https://doi.org/10.3390/jcm11092487 .
Weerink MAS, Struys MMRF, Hannivoort LN, et al. Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet. 2017;56(8):893–913. https://doi.org/10.1007/s40262-017-0507-7 .
doi: 10.1007/s40262-017-0507-7
pubmed: 28105598
pmcid: 5511603
Romagnoli S, Amigoni A, Blangetti I et al. Light sedation with dexmedetomidine: a practical approach for the intensivist in different ICU patients. Minerva Anestesiol. 2018;84(6):731-46. https://doi.org/10.23736/S0375-9393.18.12350-9 .
Lin YY, He B, Chen J, Wang ZN. Can dexmedetomidine be a safe and efficacious sedative agent in post-cardiac surgery patients? a meta-analysis. Crit Care. 2012;16(5):R169-R. https://doi.org/10.1186/cc11646 .
Shokri H, Ali I. A randomized control trial comparing prophylactic dexmedetomidine versus clonidine on rates and duration of delirium in older adult patients undergoing coronary artery bypass grafting. J Clin Anesth. 2020;61:109622-. https://doi.org/10.1016/j.jclinane.2019.09.016 .
Zi J, Fan Yo, Dong CH et al. Anxiety administrated by dexmedetomidine to prevent new-onset of postoperative atrial fibrillation in patients undergoing off-Pump coronary artery bypass graft. Int Heart J. 2020: https://doi.org/10.1536/ihj.19-132 . https://doi.org/10.1536/ihj.19-132 .
Piao GY, Wu JR. Systematic assessment of dexmedetomidine as an anesthetic agent: a meta-analysis of randomized controlled trials. Arch Med Sci. 2014;10(1):19–24. https://doi.org/10.5114/aoms.2014.40730 .
doi: 10.5114/aoms.2014.40730
pubmed: 24701209
pmcid: 3953974
Habibi V, Kiabi FH, Sharifi H. The effect of dexmedetomidine on the acute pain after cardiothoracic surgeries: a systematic review. Braz J Cardiovasc Surg. 2018;33(4):404-17. https://doi.org/10.21470/1678-9741-2017-0253 .
Penttilä J, Helminen A, Anttila M, Hinkka S, Scheinin H. Cardiovascular and parasympathetic effects of dexmedetomidine in healthy subjects. Can J Physiol Pharmacol. 2004;82(5):359–62. https://doi.org/10.1139/y04-028 .
doi: 10.1139/y04-028
pubmed: 15213737
Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology. 2000;93(2):382-94. 10.1097 / 00000542-200008000-00016.
Kang D, Lim C, Shim DJ, et al. The correlation of heart rate between natural sleep and dexmedetomidine sedation. Korean J Anesthesiol. 2019;72(2):164–8. https://doi.org/10.4097/kja.d.18.00208 .
doi: 10.4097/kja.d.18.00208
pubmed: 30481949
Yu GF, Jin SY, Chen JH, Yao WF, Song XR. The effects of novel α(2)-adrenoreceptor agonist dexmedetomidine on shivering in patients underwent caesarean section. Biosci Rep. 2019;39(2):BSR20181847. 10.1042/BSR20181847.
Geng ZY, Liu YF, Wang SS, Wang DX. Intra-operative dexmedetomidine reduces early postoperative nausea but not vomiting in adult patients after gynaecological laparoscopic surgery: a randomised controlled trial. Eur J Anaesthesiol. 2016;33(10):761–6. https://doi.org/10.1097/EJA.0000000000000491 .
doi: 10.1097/EJA.0000000000000491
pubmed: 27307217
Mahboobi SK. Dexmedetomidine and renal protection after cardiac surgery. J Clin Anesth. 2017;40:121–2. https://doi.org/10.1016/j.jclinane.2017.05.002 .
doi: 10.1016/j.jclinane.2017.05.002
pubmed: 28625433
Lin N, Vutskits L, Bebawy JF, Gelb AW. Perspectives on dexmedetomidine use for neurosurgical patients. J Neurosurg Anesthesiol. 2019;31(4):366–77. https://doi.org/10.1097/ANA.0000000000000554 .
doi: 10.1097/ANA.0000000000000554
pubmed: 30363004
Wong A, Smithburger PL, Kane-Gill SL. Review of adjunctive dexmedetomidine in the management of severe acute alcohol withdrawal syndrome. Am J Drug Alcohol Abuse. 2015;41(5):382–91. https://doi.org/10.3109/00952990.2015.1058390 .
doi: 10.3109/00952990.2015.1058390
pubmed: 26337198
Vega L, Sanchez-de-Toledo J, Gran F, et al. Prevention of opioid withdrawal syndrome after pediatric heart transplantation: usefulness of dexmedetomidine. Rev Esp Cardiol (Engl Ed). 2013;66(7):593–5. https://doi.org/10.1016/j.rec.2013.01.014 .
doi: 10.1016/j.rec.2013.01.014
pubmed: 24776215
Snapir A, Posti J, Kentala E et al. Effects of low and high plasma concentrations of dexmedetomidine on myocardial perfusion and cardiac function in healthy male subjects. Anesthesiology. 2006;105(5):902-10; quiz 1069-70. https://doi.org/10.1097/00000542-200611000-00010 .
Bao N, Tang B. Organ-protective effects and the underlying mechanism of dexmedetomidine. Mediators Inflamm. 2020;2020:6136105. https://doi.org/10.1155/2020/6136105 .
doi: 10.1155/2020/6136105
pubmed: 32454792
pmcid: 7232715
Yuki K. The immunomodulatory mechanism of dexmedetomidine. International immunopharmacology. 2021;97: 107709. https://doi.org/10.1016/j.intimp.2021.107709 .
doi: 10.1016/j.intimp.2021.107709
pubmed: 33933842
pmcid: 8324520
Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G. The molecular machinery of regulated cell death. Cell research. 2019;29(5):347–64. https://doi.org/10.1038/s41422-019-0164-5 .
doi: 10.1038/s41422-019-0164-5
pubmed: 30948788
pmcid: 6796845
He Y, Yang ZY, Li JL, Li EY. Dexmedetomidine reduces the inflammation and apoptosis of doxorubicin-induced myocardial cells. Exp Mol Pathol. 2020;113:104371-. https://doi.org/10.1016/j.yexmp.2020.104371 .
Chen S, Li A, Wu J, et al. Dexmedetomidine reduces myocardial ischemia-reperfusion injury in young mice through MIF/AMPK/GLUT4 axis. BMC Anesthesiol. 2022;22(1):289. https://doi.org/10.1186/s12871-022-01825-z .
doi: 10.1186/s12871-022-01825-z
pubmed: 36104681
pmcid: 9472426
Yuan M, Meng XW, Ma J et al. Dexmedetomidine protects H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation-induced intracellular calcium overload and apoptosis through regulating FKBP12.6/RyR2 signaling. Drug Des Devel Ther. 2019;13:3137-49. https://doi.org/10.2147/dddt.S219533 .
Yang FY, Zhang L, Zheng Y, Dong H. Dexmedetomidine attenuates ischemia and reperfusion-induced cardiomyocyte injury through p53 and forkhead box O3a (FOXO3a)/p53-upregulated modulator of apoptosis (PUMA) signaling signaling. Bioengineered. 2022;13(1):1377–87. https://doi.org/10.1080/21655979.2021.2017611 .
doi: 10.1080/21655979.2021.2017611
pubmed: 34974801
pmcid: 8805856
Peng K, Chen WR, Xia F, et al. Dexmedetomidine post-treatment attenuates cardiac ischaemia/reperfusion injury by inhibiting apoptosis through HIF-1α signalling. J Cell Mol Med. 2020;24(1):850–61. https://doi.org/10.1111/jcmm.14795 .
doi: 10.1111/jcmm.14795
pubmed: 31680420
Sun T, Gong Q, Wu Y, et al. Dexmedetomidine alleviates cardiomyocyte apoptosis and cardiac dysfunction may be associated with inhibition of RhoA/ROCK pathway in mice with myocardial infarction. Naunyn Schmiedebergs Arch Pharmacol. 2021;394(7):1569–77. https://doi.org/10.1007/s00210-021-02082-6 .
doi: 10.1007/s00210-021-02082-6
pubmed: 33782744
Zhang C, Li XY, Luo ZZ, Wu TW, Hu H. Upregulation of LINC00982 inhibits cell proliferation and promotes cell apoptosis by regulating the activity of PI3K/AKT signaling pathway in renal cancer. Eur Rev Med Pharmacol Sci. 2019;23(4):1443-50. https://doi.org/10.26355/eurrev_201902_17101 .
Wang T, Li Z, Xia S, et al. Dexmedetomidine promotes cell proliferation and inhibits cell apoptosis by regulating LINC00982 and activating the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling in hypoxia/reoxygenation-induced H9c2 cells. Bioengineered. 2022;13(4):10159–67. https://doi.org/10.1080/21655979.2022.2060900 .
doi: 10.1080/21655979.2022.2060900
pubmed: 35466860
pmcid: 9161950
Chang JH, Jin MM, Liu JT. Dexmedetomidine pretreatment protects the heart against apoptosis in ischemia/reperfusion injury in diabetic rats by activating PI3K/Akt signaling in vivo and in vitro. Biomed Pharmacother. 2020;127:110188. https://doi.org/10.1016/j.biopha.2020.110188 .
doi: 10.1016/j.biopha.2020.110188
pubmed: 32407987
Yu P, Zhang J, Ding Y, et al. Dexmedetomidine post-conditioning alleviates myocardial ischemia-reperfusion injury in rats by ferroptosis inhibition via SLC7A11/GPX4 axis activation. Hum Cell. 2022;35(3):836–48. https://doi.org/10.1007/s13577-022-00682-9 .
doi: 10.1007/s13577-022-00682-9
pubmed: 35212945
Wang C, Yuan W, Hu A, et al. Dexmedetomidine alleviated sepsis-induced myocardial ferroptosis and septic heart injury. Mol Med Rep. 2020;22(1):175–84. https://doi.org/10.3892/mmr.2020.11114 .
doi: 10.3892/mmr.2020.11114
pubmed: 32377745
pmcid: 7248514
Wang Z, Yao M, Jiang L, et al. Dexmedetomidine attenuates myocardial ischemia/reperfusion-induced ferroptosis via AMPK/GSK-3β/Nrf2 axis. Biomed Pharmacother. 2022;154: 113572. https://doi.org/10.1016/j.biopha.2022.113572 .
doi: 10.1016/j.biopha.2022.113572
pubmed: 35988428
Li F, Hu Z, Huang Y, Zhan H. Dexmedetomidine ameliorates diabetic cardiomyopathy by inhibiting ferroptosis through the Nrf2/GPX4 pathway. Journal of cardiothoracic surgery. 2023;18(1):223. https://doi.org/10.1186/s13019-023-02300-7 .
doi: 10.1186/s13019-023-02300-7
pubmed: 37430319
pmcid: 10334540
Ma X, Xu J, Gao N, Tian J, Song T. Dexmedetomidine attenuates myocardial ischemia-reperfusion injury via inhibiting ferroptosis by the cAMP/PKA/CREB pathway. Mol Cell Probes. 2023;68: 101899. https://doi.org/10.1016/j.mcp.2023.101899 .
doi: 10.1016/j.mcp.2023.101899
pubmed: 36775106
Chen X, Tian PC, Wang K, Wang M, Wang K. Pyroptosis: role and mechanisms in cardiovascular disease. Front Cardiovasc Med. 2022;9: 897815. https://doi.org/10.3389/fcvm.2022.897815 .
doi: 10.3389/fcvm.2022.897815
pubmed: 35647057
pmcid: 9130572
Zhong Y, Li YP, Yin YQ, Hu BL, Gao H. Dexmedetomidine inhibits pyroptosis by down-regulating miR-29b in myocardial ischemia reperfusion injury in rats. Int Immunopharmacol. 2020;86: 106768. https://doi.org/10.1016/j.intimp.2020.106768 .
doi: 10.1016/j.intimp.2020.106768
pubmed: 32679539
Huang Y, Sun X, Juan Z, et al. Dexmedetomidine attenuates myocardial ischemia-reperfusion injury in vitro by inhibiting NLRP3 Inflammasome activation. BMC Anesthesiol. 2021;21(1):104. https://doi.org/10.1186/s12871-021-01334-5 .
doi: 10.1186/s12871-021-01334-5
pubmed: 33823789
pmcid: 8022424
Takahashi M. Cell-specific roles of NLRP3 inflammasome in myocardial infarction. J Cardiovasc Pharmacol. 2019;74(3):188–93. https://doi.org/10.1097/fjc.0000000000000709 .
doi: 10.1097/fjc.0000000000000709
pubmed: 31356542
Wang L, Liu J, Wang Z, et al. Dexmedetomidine abates myocardial ischemia reperfusion injury through inhibition of pyroptosis via regulation of miR-665/MEF2D/Nrf2 axis. Biomed Pharmacother. 2023;165: 115255. https://doi.org/10.1016/j.biopha.2023.115255 .
doi: 10.1016/j.biopha.2023.115255
pubmed: 37549462
Yin W, Wang C, Peng Y, et al. Dexmedetomidine alleviates H(2)O(2)-induced oxidative stress and cell necroptosis through activating of α2-adrenoceptor in H9C2 cells. Mol Biol Rep. 2020;47(5):3629–39. https://doi.org/10.1007/s11033-020-05456-w .
doi: 10.1007/s11033-020-05456-w
pubmed: 32342432
Chen JY, Jiang ZZ, Zhou X, et al. Dexmedetomidine preconditioning protects cardiomyocytes against hypoxia/reoxygenation-induced necroptosis by inhibiting HMGB1-mediated inflammation. Cardiovasc Drugs Ther. 2019;33(1):45–54. https://doi.org/10.1007/s10557-019-06857-1 .
doi: 10.1007/s10557-019-06857-1
pubmed: 30675709
Shen R, Pan D, Wang Z, et al. The effects of dexmedetomidine post-conditioning on cardiac and neurological outcomes after cardiac arrest and resuscitation in swine. Shock. 2021;55(3):388–95. https://doi.org/10.1097/shk.0000000000001637 .
doi: 10.1097/shk.0000000000001637
pubmed: 32925602
Shao Q, Xia J, Wu P, Ying J. Dexmedetomidine protects cardiac microvascular endothelial cells from the damage of ogd/r through regulation of the pparδ-mediated autophagy. Microcirculation . 2021;28(4):e12675. https://doi.org/10.1111/micc.12675 .
Denton D, Kumar S. Autophagy-dependent cell death. Cell death and differentiation. 2019;26(4):605–16. https://doi.org/10.1038/s41418-018-0252-y .
doi: 10.1038/s41418-018-0252-y
pubmed: 30568239
Zhao S, Wu W, Lin X, et al. Protective effects of dexmedetomidine in vital organ injury: crucial roles of autophagy. Cell Mol Biol Lett. 2022;27(1):34. https://doi.org/10.1186/s11658-022-00335-7 .
doi: 10.1186/s11658-022-00335-7
pubmed: 35508984
pmcid: 9066865
Xiao Y, Li J, Qiu L, et al. Dexmedetomidine protects human cardiomyocytes against ischemia-reperfusion injury through α2-adrenergic receptor/AMPK-dependent autophagy. Front Pharmacol. 2021;12: 615424. https://doi.org/10.3389/fphar.2021.615424 .
doi: 10.3389/fphar.2021.615424
pubmed: 34093174
pmcid: 8176440
Singhal AK, Symons JD, Boudina S, Jaishy B, Shiu YT. Role of Endothelial Cells in Myocardial Ischemia-Reperfusion Injury. Vascular disease prevention. 2010;7:1-14. 0.2174/1874120701007010001.
Yu TY, Liu D, Gao M et al. Dexmedetomidine prevents septic myocardial dysfunction in rats via activation of α7nAChR and PI3K/Akt- mediated autophagy. Biomed Pharmacother. 2019;120:109231-. https://doi.org/10.1016/j.biopha.2019.109231 .
Oh JE, Jun JH, Hwang HJ, et al. Dexmedetomidine restores autophagy and cardiac dysfunction in rats with streptozotocin-induced diabetes mellitus. Acta Diabetol. 2019;56(1):105–14. https://doi.org/10.1007/s00592-018-1225-9 .
doi: 10.1007/s00592-018-1225-9
pubmed: 30206697
Li Y, Qu M, Xing F, et al. The protective mechanism of dexmedetomidine in regulating Atg14L-Beclin1-Vps34 complex against myocardial ischemia-reperfusion injury. J Cardiovasc Trans Res. 2021;14(6):1063–74. https://doi.org/10.1007/s12265-021-10125-9 .
doi: 10.1007/s12265-021-10125-9
Rotter Sopasakis V, Sandstedt J, Johansson M, et al. Toll-like receptor-mediated inflammation markers are strongly induced in heart tissue in patients with cardiac disease under both ischemic and non-ischemic conditions. Int J Cardiol. 2019;293:238–47. https://doi.org/10.1016/j.ijcard.2019.06.033 .
doi: 10.1016/j.ijcard.2019.06.033
pubmed: 31230935
Gao JM, Meng XW, Zhang J et al. Dexmedetomidine protects cardiomyocytes against hypoxia/reoxygenation injury by suppressing TLR4-MyD88-NF-κB signaling. Biomed Res Int. 2017;2017:1674613-. https://doi.org/10.1155/2017/1674613 .
Yang YF, Peng K, Liu H, et al. Dexmedetomidine preconditioning for myocardial protection in ischaemia-reperfusion injury in rats by downregulation of the high mobility group box 1-toll-like receptor 4-nuclear factor κB signalling pathway. Clin Exp Pharmacol Physiol. 2017;44(3):353–61. https://doi.org/10.1111/1440-1681.12711 .
doi: 10.1111/1440-1681.12711
pubmed: 27998004
Zhang JJ, Peng K, Zhang J, Meng XW, Ji FH. Dexmedetomidine preconditioning may attenuate myocardial ischemia/reperfusion injury by down-regulating the HMGB1-TLR4-MyD88-NF-кB signaling pathway. PLoS One. 2017;12(2): e0172006. https://doi.org/10.1371/journal.pone.0172006 .
doi: 10.1371/journal.pone.0172006
pubmed: 28222157
pmcid: 5319750
Yuan T, Yang Z, Xian S, et al. Dexmedetomidine-mediated regulation of miR-17-3p in H9C2 cells after hypoxia/reoxygenation injury. Exp Ther Med. 2020;20(2):917–25. https://doi.org/10.3892/etm.2020.8775 .
doi: 10.3892/etm.2020.8775
pubmed: 32742334
pmcid: 7388268
Zhang J, Xia F, Zhao HF et al. Dexmedetomidine-induced cardioprotection is mediated by inhibition of high mobility group box-1 and the cholinergic anti-inflammatory pathway in myocardial ischemia-reperfusion injury. PLoS One. 2019;14(7):e0218726-e. https://doi.org/10.1371/journal.pone.0218726 .
Kong W, Kang K, Gao Y, et al. Dexmedetomidine alleviates LPS-induced septic cardiomyopathy via the cholinergic anti-inflammatory pathway in mice. Am J Transl Res. 2017;9(11):5040–7.
pubmed: 29218102
pmcid: 5714788
Xiong W, Zhou R, Qu Y, et al. Dexmedetomidine preconditioning mitigates myocardial ischemia/reperfusion injury via inhibition of mast cell degranulation. Biomed Pharmacother. 2021;141: 111853. https://doi.org/10.1016/j.biopha.2021.111853 .
doi: 10.1016/j.biopha.2021.111853
pubmed: 34237593
Zhang B, Zhang J, Ainiwaer Y, et al. Dexmedetomidine attenuates myocardial injury induced by renal ischemia/reperfusion by inhibiting the HMGB1-TLR4-MyD88-NF-κB signaling pathway. Ann Clin Lab Sci. 2021;51(3):376–84.
pubmed: 34162568
Zheng X, Li J, Fan Q, Zhao X, Chen K. Dexmedetomidine alleviates myocardial ischemia/reperfusion-induced injury and Ca(2+) overload via the microRNA-346-3p/CaMKIId axis. Int J Cardiol. 2021;338:185–95. https://doi.org/10.1016/j.ijcard.2021.03.016 .
doi: 10.1016/j.ijcard.2021.03.016
pubmed: 33731281
Pang Q, You L, Meng X, et al. Regulation of the JAK/STAT signaling pathway: the promising targets for cardiovascular disease. Biochem Pharmacol. 2023;213: 115587. https://doi.org/10.1016/j.bcp.2023.115587 .
doi: 10.1016/j.bcp.2023.115587
pubmed: 37187275
Chen ZR, Hong Y, Wen SH, Zhan YQ, Huang WQ. Dexmedetomidine pretreatment protects against myocardial ischemia/reperfusion injury by activating STAT3 signaling. Anesth Analg. 2023. https://doi.org/10.1213/ane.0000000000006487 .
doi: 10.1213/ane.0000000000006487
pubmed: 38100810
pmcid: 10629609
Pan S, Chen Y, Zhang X, Xie Y. The JAK2/STAT3 pathway is involved in dexmedetomidine-induced myocardial protection in rats undergoing cardiopulmonary bypass. Ann Transl Med. 2020;8(7):483. https://doi.org/10.21037/atm.2020.03.67 .
Kurdi M, Booz GW. Can the protective actions of JAK-STAT in the heart be exploited therapeutically? Parsing the regulation of interleukin-6-type cytokine signaling. J Cardiovasc Pharmacol. 2007;50(2):126–41. https://doi.org/10.1097/FJC.0b013e318068dd49 .
doi: 10.1097/FJC.0b013e318068dd49
pubmed: 17703129
Comità S, Femmino S, Thairi C, et al. Regulation of STAT3 and its role in cardioprotection by conditioning: focus on non-genomic roles targeting mitochondrial function. Basic research in cardiology. 2021;116(1):56. https://doi.org/10.1007/s00395-021-00898-0 .
doi: 10.1007/s00395-021-00898-0
pubmed: 34642818
pmcid: 8510947
Shi X, Liu Z, Li J. Protective effects of dexmedetomidine on hypoxia/reoxygenation injury in cardiomyocytes by regulating the CHOP signaling pathway. Mol Med Rep. 2020;22(4):3307–15. https://doi.org/10.3892/mmr.2020.11442 .
doi: 10.3892/mmr.2020.11442
pubmed: 32945482
pmcid: 7453597
Chen WL, Jin N, Lin YY, et al. Immunomodulatory effects of fentanyl or dexmedetomidine hydrochloride infusion after allogeneic heart transplantation in mice. Reg Anesth Pain Med. 2018;43(5):509–15. https://doi.org/10.1097/AAP.0000000000000747 .
doi: 10.1097/AAP.0000000000000747
pubmed: 29509567
Ma Y, Yu XY, Wang Y. Dose-related effects of dexmedetomidine on immunomodulation and mortality to septic shock in rats. World J Emerg Med. 2018;9(1):56–63. https://doi.org/10.5847/wjem.j.1920-8642.2018.01.009 .
doi: 10.5847/wjem.j.1920-8642.2018.01.009
pubmed: 29290897
pmcid: 5717378
Dardalas I, Stamoula E, Rigopoulos P et al. Dexmedetomidine effects in different experimental sepsis in vivo models. Eur J Pharmacol. 2019;856:172401-. https://doi.org/10.1016/j.ejphar.2019.05.030 .
Sharma A, Tate M, Mathew G, et al. Oxidative stress and NLRP3-inflammasome activity as significant drivers of diabetic cardiovascular complications: therapeutic implications. Front Physiol. 2018;9:114. https://doi.org/10.3389/fphys.2018.00114 .
doi: 10.3389/fphys.2018.00114
pubmed: 29515457
pmcid: 5826188
Wang YG, Liu CZ, Li YZ, Peng Y, Yan SL. Cotreatments with Dex and Na(2)SeO(3) further improved antioxidant and anti-inflammatory protection of myocardial cells from I/R injury compared to their individual treatments. Free Radic Res. 2020;54(1):76–90. https://doi.org/10.1080/10715762.2019.1707198 .
doi: 10.1080/10715762.2019.1707198
pubmed: 31909644
Wu ZL, Davis JRJ, Zhu Y. Dexmedetomidine protects against myocardial ischemia/reperfusion injury by ameliorating oxidative stress and cell apoptosis through the Trx1-dependent Akt pathway. Biomed Res Int. 2020;2020:8979270. https://doi.org/10.1155/2020/8979270 .
doi: 10.1155/2020/8979270
pubmed: 33299886
pmcid: 7710428
Zhang J, Jiang H, Liu DH, Wang GN. Effects of dexmedetomidine on myocardial ischemia-reperfusion injury through PI3K-Akt-mTOR signaling pathway. Eur Rev Med Pharmacol Sci. 2019;23(15):6736-43. https://doi.org/10.26355/eurrev_201908_18565 .
Cheng XY, Hu J, Wang Y, et al. Effects of dexmedetomidine postconditioning on myocardial ischemia/reperfusion injury in diabetic rats: role of the PI3K/Akt-dependent signaling pathway. J Diabetes Res. 2018;2018:3071959-. https://doi.org/10.1155/2018/3071959 .
Hu B, Tian T, Li XT, et al. Dexmedetomidine postconditioning attenuates myocardial ischemia/reperfusion injury by activating the Nrf2/Sirt3/SOD2 signaling pathway in the rats. Redox Rep. 2023;28(1):2158526. https://doi.org/10.1080/13510002.2022.2158526 .
doi: 10.1080/13510002.2022.2158526
pubmed: 36738240
pmcid: 9904316
Li HX, Wang TH, Wu LX, et al. Role of Keap1-Nrf2/ARE signal transduction pathway in protection of dexmedetomidine preconditioning against myocardial ischemia/reperfusion injury. 2022. Biosci Rep. https://doi.org/10.1042/bsr20221306 .
Wu W, Du Z, Wu L. Dexmedetomidine attenuates hypoxia-induced cardiomyocyte injury by promoting telomere/telomerase activity: Possible involvement of ERK1/2-Nrf2 signaling pathway. Cell Biol Int. 2022;46(7):1036–46. https://doi.org/10.1002/cbin.11799 .
doi: 10.1002/cbin.11799
pubmed: 35312207
Borger M, von Haefen C, Bührer C, Endesfelder S. Cardioprotective Effects of Dexmedetomidine in an Oxidative-Stress In Vitro Model of Neonatal Rat Cardiomyocytes. Antioxidants (Basel, Switzerland). 2023;12(6). https://doi.org/10.3390/antiox12061206 .
Gao W, Du L, Li N, et al. Dexmedetomidine attenuates myocardial ischemia-reperfusion injury in hyperlipidemic rats by inhibiting inflammation, oxidative stress and NF-κB. Chemical biology & drug design. 2023;102(5):1176–85. https://doi.org/10.1111/cbdd.14324 .
doi: 10.1111/cbdd.14324
Zhu Z, Ling X, Zhou H, Zhang C. Dexmedetomidine at a dose of 1 µM attenuates H9c2 cardiomyocyte injury under 3 h of hypoxia exposure and 3 h of reoxygenation through the inhibition of endoplasmic reticulum stress. Exp Ther Med. 2021;21(2):132. https://doi.org/10.3892/etm.2020.9564 .
doi: 10.3892/etm.2020.9564
pubmed: 33376514
Liu XR, Li T, Cao L, et al. Dexmedetomidine attenuates H2O2-induced neonatal rat cardiomyocytes apoptosis through mitochondria- and ER-medicated oxidative stress pathways. Mol Med Rep. 2018;17(5):7258–64. https://doi.org/10.3892/mmr.2018.8751 .
doi: 10.3892/mmr.2018.8751
pubmed: 29568958
pmcid: 5928682
Yang YF, Wang H, Song N, et al. Dexmedetomidine attenuates ischemia/reperfusion-induced myocardial inflammation and apoptosis through inhibiting endoplasmic reticulum stress signaling. J Inflam Res. 2021;14:1217–33. https://doi.org/10.2147/jir.S292263 .
doi: 10.2147/jir.S292263
Zhang Y, Zhao Q, Li X, Ji F. Dexmedetomidine reversed hypoxia/reoxygenation injury-induced oxidative stress and endoplasmic reticulum stress-dependent apoptosis of cardiomyocytes via SIRT1/CHOP signaling pathway. Mol Cell Biochem. 2021;476(7):2803–12. https://doi.org/10.1007/s11010-021-04102-8 .
doi: 10.1007/s11010-021-04102-8
pubmed: 33725228
Wang L, Wang S, Jia T, et al. Dexmedetomidine prevents cardiomyocytes from hypoxia/reoxygenation injury via modulating tetmethylcytosine dioxygenase 1-mediated DNA demethylation of Sirtuin1. Bioengineered. 2022;13(4):9369–86. https://doi.org/10.1080/21655979.2022.2054762 .
doi: 10.1080/21655979.2022.2054762
pubmed: 35387565
pmcid: 9161963
Zhu Z, Ling X, Zhou H, Zhang C, Yan W. Dexmedetomidine attenuates cellular injury and apoptosis in H9c2 cardiomyocytes by regulating p-38MAPK and endoplasmic reticulum stress. Drug Des Devel Ther. 2020;14:4231–43. https://doi.org/10.2147/dddt.S265970 .
doi: 10.2147/dddt.S265970
pubmed: 33116411
pmcid: 7568428
Chu Y, Teng J, Feng P, et al. Dexmedetomidine attenuates hypoxia/reoxygenation injury of H9C2 myocardial cells by upregulating miR-146a expression via the MAPK signal pathway. Pharmacology. 2022;107(1–2):14–27. https://doi.org/10.1159/000506814 .
doi: 10.1159/000506814
pubmed: 34718238
Mitra A, Ray A, Datta R, Sengupta S, Sarkar S. Cardioprotective role of P38 MAPK during myocardial infarction via parallel activation of α-crystallin B and Nrf2. J Cell Physiol. 2014;229(9):1272–82. https://doi.org/10.1002/jcp.24565 .
doi: 10.1002/jcp.24565
pubmed: 24464634
Zou H, Liu G. Inhibition of endoplasmic reticulum stress through activation of MAPK/ERK signaling pathway attenuates hypoxia-mediated cardiomyocyte damage. J Recep Signal Transduct Res. 2021;41(6):532–7. https://doi.org/10.1080/10799893.2020.1831534 .
doi: 10.1080/10799893.2020.1831534
Saurin AT, Martin JL, Heads RJ, et al. The role of differential activation of p38-mitogen-activated protein kinase in preconditioned ventricular myocytes. FASEB J. 2000;14(14):2237–46. https://doi.org/10.1096/fj.99-0671com .
doi: 10.1096/fj.99-0671com
pubmed: 11053245
Li JJ, Zhao Y, Zhou N, Li LY, Li K. Dexmedetomidine attenuates myocardial ischemia-reperfusion injury in diabetes mellitus by inhibiting endoplasmic reticulum stress. J Diabetes Res. 2019;2019:7869318-. https://doi.org/10.1155/2019/7869318 .
Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140(6):821–32. https://doi.org/10.1016/j.cell.2010.01.040 .
doi: 10.1016/j.cell.2010.01.040
pubmed: 20303873
Ong G, Logue SE. Unfolding the Interactions between Endoplasmic Reticulum Stress and Oxidative Stress. Antioxidants (Basel, Switzerland). 2023;12(5). https://doi.org/10.3390/antiox12050981 .
Weng XJ, Zhang XD, Lu XF, Wu J, Li ST. Reduced mitochondrial response sensitivity is involved in the anti-apoptotic effect of dexmedetomidine pretreatment in cardiomyocytes. Int J Mol Med. 2018;41(4):2328–38. https://doi.org/10.3892/ijmm.2018.3384 .
doi: 10.3892/ijmm.2018.3384
pubmed: 29328437
Yu JL, Jin Y, Cao XY, Gu HH. Dexmedetomidine alleviates doxorubicin cardiotoxicity by inhibiting mitochondrial reactive oxygen species generation. Hum Cell. 2020;33(1):47–56. https://doi.org/10.1007/s13577-019-00282-0 .
doi: 10.1007/s13577-019-00282-0
pubmed: 31643023
Deng X, Ye F, Zeng L, et al. Dexmedetomidine Mitigates myocardial ischemia/reperfusion-induced mitochondrial apoptosis through targeting lncRNA HCP5. Am J Chin Med. 2022;50(6):1529–51. https://doi.org/10.1142/s0192415x22500641 .
doi: 10.1142/s0192415x22500641
pubmed: 35931662
Kulek AR, Anzell A, Wider JM, Sanderson TH, Przyklenk K. Mitochondrial quality control: role in cardiac models of lethal ischemia-reperfusion injury. Cells. 2020;9(1). https://doi.org/10.3390/cells9010214 .
Jiang CC, Xia ML, Wang M, Chen SP. Dexmedetomidine preconditioning protects isolated rat hearts against ischemia/reperfusion injuries and its mechanism. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2013;42(3):326–30.
pubmed: 23801622
Behmenburg F, Pickert E, Mathes A, et al. The Cardioprotective Effect of Dexmedetomidine in Rats Is Dose-Dependent and Mediated by BKCa Channels. J Cardiovasc Pharmacol. 2017;69(4):228–35. https://doi.org/10.1097/fjc.0000000000000466 .
doi: 10.1097/fjc.0000000000000466
pubmed: 28375904
Raupach A, Karakurt E, Torregroza C, et al. Dexmedetomidine provides cardioprotection during early or late reperfusion mediated by different mitochondrial K+-channels. Anesth Analg. 2021;132(1):253–60. https://doi.org/10.1213/ane.0000000000005148 .
doi: 10.1213/ane.0000000000005148
pubmed: 32889843
Du J, Xu Z, Zhen J et al. Dexmedetomidine attenuates myocardial ischemia/reperfusion injury through regulating lactate signaling cascade in mice. Eur Rev Med Pharmacol Sci. 2019;23(8):3527-32. https://doi.org/10.26355/eurrev_201904_17721 .
She H, Zhu Y, Deng H, et al. Protective Effects of Dexmedetomidine on the Vascular Endothelial Barrier Function by Inhibiting Mitochondrial Fission via ER/Mitochondria Contact. Front Cell Develop Biol. 2021;9: 636327. https://doi.org/10.3389/fcell.2021.636327 .
doi: 10.3389/fcell.2021.636327
Sun YJ, Jiang C, Jiang J, Qiu LS. Dexmedetomidine protects mice against myocardium ischaemic/reperfusion injury by activating an AMPK/PI3K/Akt/eNOS pathway. Clin Exp Pharmacol Physiol. 2017;44(9):946–53. https://doi.org/10.1111/1440-1681.12791 .
doi: 10.1111/1440-1681.12791
pubmed: 28556946
Riquelme JA, Westermeier F, Hall AR, et al. Dexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial eNOS/NO dependent mechanism. Pharmacol Res. 2016;103:318–27. https://doi.org/10.1016/j.phrs.2015.11.004 .
doi: 10.1016/j.phrs.2015.11.004
pubmed: 26607864
He L, Hao SQ, Wang YQ et al. Dexmedetomidine preconditioning attenuates ischemia/reperfusion injury in isolated rat hearts with endothelial dysfunction. Biomed Pharmacother. 2019;114:108837. https://doi.org/10.1016/j.biopha.2019.108837 .
Tang X, Zhang C, Tian T, et al. Posttreatment with dexmedetomidine aggravates LPS-induced myocardial dysfunction partly via activating cardiac endothelial α(2A)-AR in mice. Int Immunopharmacol. 2023;116:109724. https://doi.org/10.1016/j.intimp.2023.109724 .
doi: 10.1016/j.intimp.2023.109724
pubmed: 36696856
Yoshikawa Y, Hirata N, Kawaguchi R, Tokinaga Y, Yamakage M. Dexmedetomidine maintains its direct cardioprotective effect against ischemia/reperfusion injury in hypertensive hypertrophied myocardium. Anesth Analg. 2018;126(2):443–52. https://doi.org/10.1213/ANE.0000000000002452 .
doi: 10.1213/ANE.0000000000002452
pubmed: 28914648
Maltsev AV, Evdokimovskii EV, Kokoz YM. α2-Adrenoceptor signaling in cardiomyocytes of spontaneously hypertensive rats starts to impair already at early age. Biochem Biophys Research Commun. 2019;512(4):908–13. https://doi.org/10.1016/j.bbrc.2019.03.117 .
doi: 10.1016/j.bbrc.2019.03.117
Chai YF, Yu RY, Liu Y et al. Dexmedetomidine attenuates monocyte-endothelial adherence via inhibiting connexin43 on vascular endothelial cells. Mediators Inflamm. 2020;2020:7039854-. https://doi.org/10.1155/2020/7039854 .
Miranda ML, Balarini MM, Bouskela E. Dexmedetomidine attenuates the microcirculatory derangements evoked by experimental sepsis. Anesthesiology. 2015;122(3):619–30. https://doi.org/10.1097/ALN.0000000000000491 .
doi: 10.1097/ALN.0000000000000491
pubmed: 25313879
Arslan M, Comu FM, Kip G, et al. Effect of dexmedetomidine on erythrocyte deformability during ischaemia-reperfusion injury of heart in diabetic rats. Bratisl Lek Listy. 2014;115(8):494–7. https://doi.org/10.4149/bll_2014_096 .
doi: 10.4149/bll_2014_096
pubmed: 25246286
Han H, Dai DP, Hu JQ, et al. Dexmedetomidine improves cardiac function and protects against maladaptive remodeling following myocardial infarction. Mol Med Rep. 2019;20(6):5183–9. https://doi.org/10.3892/mmr.2019.10774 .
doi: 10.3892/mmr.2019.10774
pubmed: 31661145
pmcid: 6854534
Wu SJ, Lin ZH, Lin YZ, et al. Dexmedetomidine exerted anti-arrhythmic effects in rat with ischemic cardiomyopathy via upregulation of connexin 43 and reduction of fibrosis and inflammation. Front Physiol. 2020;11:33-. https://doi.org/10.3389/fphys.2020.00033 .
Liao J, Li K, Su X, et al. Dexmedetomidine promotes lipopolysaccharide-induced differentiation of cardiac fibroblasts and collagen I/III synthesis through α(2A) adrenoreceptor-mediated activation of the PKC-p38-Smad2/3 signaling pathway in mice. Int J Mol Sci. 2021;22(23). https://doi.org/10.3390/ijms222312749 .
Siebert V, Allencherril J, Ye Y, Wehrens XHT, Birnbaum Y. The role of non-coding RNAs in ischemic myocardial reperfusion injury. Cardiovasc Drugs Ther. 2019;33(4):489–98. https://doi.org/10.1007/s10557-019-06893-x .
doi: 10.1007/s10557-019-06893-x
pubmed: 31332654
Wang LY, Tang SM, Wang ZR et al. The administration of dexmedetomidine changes microRNA expression profiling of rat hearts. Biomed Pharmacother. 2019;120:109463-. https://doi.org/10.1016/j.biopha.2019.109463 .
Yang XH, Chen HM, Chen Y, et al. Circulating miRNA expression profiling and target prediction in patients receiving dexmedetomidine. Cell Physiol Biochem. 2018;50(2):552–68. https://doi.org/10.1159/000494168 .
doi: 10.1159/000494168
pubmed: 30308506
Cai X, Li B, Wei W, et al. Circulating microRNA-30a-5p, microRNA-101-3p, microRNA-140-3p and microRNA-141-3p as potential biomarkers for dexmedetomidine response in pediatric patients. Eur J Clin Pharmacol. 2021;77(12):1853–9. https://doi.org/10.1007/s00228-021-03178-x .
doi: 10.1007/s00228-021-03178-x
pubmed: 34216249
Yoshikawa Y, Hirata N, Terada H, Sawashita Y, Yamakage M. Identification of candidate genes and pathways in dexmedetomidine-induced cardioprotection in the rat heart by bioinformatics analysis. Int J Mol Sci. 2019;20(7):1614. https://doi.org/10.3390/ijms20071614 .
doi: 10.3390/ijms20071614
pubmed: 30939728
pmcid: 6480577
Wang Z, Yang Y, Xiong W, et al. Dexmedetomidine protects H9C2 against hypoxia/reoxygenation injury through miR-208b-3p/Med13/Wnt signaling pathway axis. Biomed Pharmacother. 2020;125: 110001. https://doi.org/10.1016/j.biopha.2020.110001 .
doi: 10.1016/j.biopha.2020.110001
pubmed: 32070878
Guo P, Yi H, Han M, et al. Dexmedetomidine alleviates myocardial ischemia-reperfusion injury by down-regulating miR-34b-3p to activate the Jagged1/Notch signaling pathway. Int Immunopharmacol. 2023;116: 109766. https://doi.org/10.1016/j.intimp.2023.109766 .
doi: 10.1016/j.intimp.2023.109766
pubmed: 36764271
Yu J, Yang W, Wang W et al. Involvement of miR-665 in protection effect of dexmedetomidine against Oxidative Stress Injury in myocardial cells via CB2 and CK1. Biomed Pharmacother. 2019;115:108894-. https://doi.org/10.1016/j.biopha.2019.108894 .
He L, Wang Z, Zhou R, et al. Dexmedetomidine exerts cardioprotective effect through miR-146a-3p targeting IRAK1 and TRAF6 via inhibition of the NF-κB pathway. Biomed Pharmacother. 2021;133: 110993. https://doi.org/10.1016/j.biopha.2020.110993 .
doi: 10.1016/j.biopha.2020.110993
pubmed: 33220608
Liu C, Xu R. Dexmedetomidine protects H9C2 rat cardiomyocytes against hypoxia/reoxygenation injury by regulating the long non-coding RNA colon cancer-associated transcript 1/microRNA-8063/Wnt/β-catenin axis. Bioengineered. 2022;13(5):13300–11. https://doi.org/10.1080/21655979.2022.2080420 .
doi: 10.1080/21655979.2022.2080420
pubmed: 35635079
pmcid: 9275899
Chang Y, Xing L, Zhou W, Zhang W. Up-regulating microRNA-138-5p enhances the protective role of dexmedetomidine on myocardial ischemia-reperfusion injury mice via down-regulating Ltb4r1. Cell cycle (Georgetown, Tex). 2021;20(4):445–58. https://doi.org/10.1080/15384101.2021.1878330 .
doi: 10.1080/15384101.2021.1878330
pubmed: 33509010
pmcid: 7894414
Deng Y, Cai L, Wang F, et al. Upregulated microRNA-381-5p strengthens the effect of dexmedetomidine preconditioning to protect against myocardial ischemia-reperfusion injury in mouse models by inhibiting CHI3L1. Int Immunopharmacol. 2021;92: 107326. https://doi.org/10.1016/j.intimp.2020.107326 .
doi: 10.1016/j.intimp.2020.107326
pubmed: 33461162
Laggerbauer B, Engelhardt S. MicroRNAs as therapeutic targets in cardiovascular disease. The Journal of clinical investigation. 2022;132(11). https://doi.org/10.1172/jci159179 .
Silpa AR, Koshy KA, Subramanian A, Pradeep KK. Comparison of the efficacy of two doses of dexmedetomidine in attenuating the hemodynamic response to intubation in patients undergoing elective cardiac surgery: A randomized double-blinded study. J Anaesthesiol Clin Pharmacol. 2020;36(1):83–7. https://doi.org/10.4103/joacp.JOACP_235_18 .
doi: 10.4103/joacp.JOACP_235_18
pubmed: 32174664
pmcid: 7047691
Tan C, Yan S, Shen J, et al. Effects of dexmedetomidine on cardiac electrophysiology in patients undergoing general anesthesia during perioperative period: a randomized controlled trial. BMC Anesthesiol. 2022;22(1):271. https://doi.org/10.1186/s12871-022-01811-5 .
doi: 10.1186/s12871-022-01811-5
pubmed: 36008759
pmcid: 9404616
Ellermann C, Brandt J, Wolfes J, et al. Safe electrophysiologic profile of dexmedetomidine in different experimental arrhythmia models. Scientific reports. 2021;11(1):23940. https://doi.org/10.1038/s41598-021-03364-y .
doi: 10.1038/s41598-021-03364-y
pubmed: 34907251
pmcid: 8671395
Deng L, Chen H, Wei N, Zhang ZD, Wang GN. The cardioprotective effect of dexmedetomidine on regional ischemia/reperfusion injury in type 2 diabetic rat hearts. Microvasc Res. 2019;123:1–6. https://doi.org/10.1016/j.mvr.2018.08.006 .
doi: 10.1016/j.mvr.2018.08.006
pubmed: 30179598
Gautam NK, Turiy Y, Srinivasan C. Preincision initiation of dexmedetomidine maximally reduces the risk of junctional ectopic tachycardia in children undergoing ventricular septal defect repairs. J Cardiothorac Vasc Anesth. 2017;31(6):1960–5. https://doi.org/10.1053/j.jvca.2017.04.010 .
doi: 10.1053/j.jvca.2017.04.010
pubmed: 28774644
Shuplock JM, Smith AH, Owen J, et al. Association between perioperative dexmedetomidine and arrhythmias after surgery for congenital heart disease. Circ Arrhythm Electrophysiol. 2015;8(3):643–50. https://doi.org/10.1161/CIRCEP.114.002301 .
doi: 10.1161/CIRCEP.114.002301
pubmed: 25878324
pmcid: 4472529
Ueno K, Ninomiya Y, Shiokawa N, et al. Dexmedetomidine is associated with an increased incidence of bradycardia in patients with trisomy 21 after surgery for congenital heart disease. Pediatr Cardiol. 2016;37(7):1228–34. https://doi.org/10.1007/s00246-016-1421-8 .
doi: 10.1007/s00246-016-1421-8
pubmed: 27272693
Turan A, Duncan A, Leung S, et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet (London, England). 2020;396(10245):177–85. https://doi.org/10.1016/s0140-6736(20)30631-0 .
doi: 10.1016/s0140-6736(20)30631-0
pubmed: 32682483
Goins AE, Rayson R, Caughey MC, et al. Correlation of infarct size with invasive hemodynamics in patients with ST-elevation myocardial infarction. Catheter Cardiovasc Intervent. 2018;92(5):E333-e40. https://doi.org/10.1002/ccd.27625 .
doi: 10.1002/ccd.27625
Wang K, Wu M, Xu J, et al. Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis. Br J Anaesth. 2019;123(6):777–94. https://doi.org/10.1016/j.bja.2019.07.027 .
doi: 10.1016/j.bja.2019.07.027
pubmed: 31668347
Wang D, Lin Q, Du M et al. Protective effect of dexmedetomidine on perioperative myocardial injury in patients with Stanford type-A aortic dissection. Revista da Associacao Medica Brasileira (1992). 2020;66(12):1638-44. https://doi.org/10.1590/1806-9282.66.12.1638 .
Cui J, Gao M, Huang H, Huang X, Zeng Q. Dexmedetomidine improves lung function by promoting inflammation resolution in patients undergoing totally thoracoscopic cardiac surgery. Oxid Med Cell Longev. 2020;2020:8638301. https://doi.org/10.1155/2020/8638301 .
doi: 10.1155/2020/8638301
pubmed: 32963704
pmcid: 7495214
Wu H, Tang J, Pan J, et al. Effects of dexmedetomidine on stress hormones in patients undergoing cardiac valve replacement: a randomized controlled trial. BMC Anesthesiol. 2020;20(1):142. https://doi.org/10.1186/s12871-020-00993-0 .
doi: 10.1186/s12871-020-00993-0
pubmed: 32505177
pmcid: 7275125
Zakkar M, Ascione R, James AF, Angelini GD, Suleiman MS. Inflammation, oxidative stress and postoperative atrial fibrillation in cardiac surgery. Pharmacol Ther. 2015;154:13–20. https://doi.org/10.1016/j.pharmthera.2015.06.009 .
doi: 10.1016/j.pharmthera.2015.06.009
pubmed: 26116810
Pang Y, Li Y, Zhang Y, et al. Effects of inflammation and oxidative stress on postoperative delirium in cardiac surgery. Front Cardiovasc Med. 2022;9:1049600. https://doi.org/10.3389/fcvm.2022.1049600 .
doi: 10.3389/fcvm.2022.1049600
pubmed: 36505383
pmcid: 9731159
Li AW, Yuen VMY, Goulay-Dufay S, Kwok PCL. Pharmacokinetics and pharmacodynamics of dexmedetomidine. Drug Dev Ind Pharm. 2016;42(12):1917–27. https://doi.org/10.1080/03639045.2016.1232727 .
doi: 10.1080/03639045.2016.1232727
pubmed: 27595299
Choi YJ, Park KH, Park JY, Min WK, Lee YS. The effect of alpha-2A adrenergic receptor (ADRA2A) genetic polymorphisms on the depth of sedation of dexmedetomidine: a genetic observational pilot study. Brazil J Anesthesiol. 2022;72(2):241–6. https://doi.org/10.1016/j.bjane.2021.04.005 .
doi: 10.1016/j.bjane.2021.04.005
Yağar S, Yavaş S, Karahalil B. The role of the ADRA2A C1291G genetic polymorphism in response to dexmedetomidine on patients undergoing coronary artery surgery. Mol Biol Rep. 2011;38(5):3383–9. https://doi.org/10.1007/s11033-010-0446-y .
doi: 10.1007/s11033-010-0446-y
pubmed: 21104443
Zhu SJ, Wang KR, Zhang XX, Zhu SM. Relationship between genetic variation in the α(2A)-adrenergic receptor and the cardiovascular effects of dexmedetomidine in the Chinese Han population. J Zhejiang Univ Sci B. 2019;20(7):598–604. https://doi.org/10.1631/jzus.B1800647 .
doi: 10.1631/jzus.B1800647
pubmed: 31168973
pmcid: 6586997
Friesen RH, Slavov D, Miyamoto SD, et al. Lack of association between adrenoreceptor genotype and the vasoconstriction response to dexmedetomidine. Semin Cardiothorac Vasc Anesth. 2017;21(4):341–4. https://doi.org/10.1177/1089253217708621 .
doi: 10.1177/1089253217708621
pubmed: 28482761
Gallaway KA, Skaar TC, Biju A, Slaven J, Tillman EM. A pilot study of ADRA2A genotype association with doses of dexmedetomidine for sedation in pediatric patients. Pharmacotherapy. 2022;42(6):453–9. https://doi.org/10.1002/phar.2684 .
doi: 10.1002/phar.2684
pubmed: 35429176
pmcid: 9325491
Fang C, Ouyang W, Zeng Y, et al. CYP2A6 and GABRA2 gene polymorphisms are associated with dexmedetomidine drug response. Front Pharmacol. 2022;13:943200. https://doi.org/10.3389/fphar.2022.943200 .
doi: 10.3389/fphar.2022.943200
pubmed: 35873555
pmcid: 9301121
Ling Y, Gao H, Wang J, et al. Effects of dexmedetomidine and ACE genotype on cardiovascular response during the decannulation period of general anesthesia in patients with essential hypertension. Clin Ther. 2020;42(10):1992–2000. https://doi.org/10.1016/j.clinthera.2020.07.012 .
doi: 10.1016/j.clinthera.2020.07.012
pubmed: 32839029
Li YY, Ge DJ, Li JY, Qi B. Sex differences in the morphine-sparing effects of intraoperative dexmedetomidine in patient-controlled analgesia following general anesthesia: a consort-prospective, randomized, controlled clinical trial. Medicine. 2016;95(18): e3619. https://doi.org/10.1097/md.0000000000003619 .
doi: 10.1097/md.0000000000003619
pubmed: 27149500
pmcid: 4863817
Holliday SF, Kane-Gill SL, Empey PE, Buckley MS, Smithburger PL. Interpatient variability in dexmedetomidine response: a survey of the literature. Sci World J. 2014;2014: 805013. https://doi.org/10.1155/2014/805013 .
doi: 10.1155/2014/805013
Davy A, Fessler J, Fischler M, Le Guen M. Dexmedetomidine and general anesthesia: a narrative literature review of its major indications for use in adults undergoing non-cardiac surgery. Minerva Anestesiol. 2017;83(12):1294-308. https://doi.org/10.23736/S0375-9393.17.12040-7 .