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Review Open Access

Brain‑heart axis: Neurostimulation techniques in ischemic heart disease (Review)

  • Authors:
    • Yunnan Liu
    • Haimei Yang
    • Jian Xiong
    • Ying Wei
    • Chen Yang
    • Qianhua Zheng
    • Fanrong Liang
  • View Affiliations / Copyright

    Affiliations: The Acupuncture and Massage Institute of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, P.R. China, School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 148
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    Published online on: July 17, 2025
       https://doi.org/10.3892/ijmm.2025.5589
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Abstract

Ischemic heart disease (IHD), mainly due to atherosclerosis and coronary microvascular dysfunction, continues to be a major cause of mortality worldwide. This condition can escalate to severe complications, including heart failure, arrhythmias and sudden cardiac mortality. In advanced stages, treatments such as coronary artery bypass grafting or percutaneous coronary intervention may be necessary. The brain‑heart axis, which facilitates the interaction between the central nervous system and the cardiovascular system via the autonomic nervous system, is crucial in the management of IHD. An imbalance in autonomic function, marked by increased sympathetic activity and diminished parasympathetic influence, can worsen cardiovascular conditions by promoting inflammation, vasoconstriction and myocardial ischemia. Innovative treatments such as spinal cord stimulation and vagus nerve stimulation show potential in re‑establishing autonomic equilibrium and improving cardiovascular function by influencing the neurocardiac interface. The present review discussed the pathophysiology of IHD and methodically examined the role of the nervous system in this disease. It emphasized the possibilities of neural modulation therapy, while identifying ongoing challenges and areas lacking in current knowledge.
View Figures

Figure 1

Normal structure and function of the
coronary macrocirculation and microcirculation. The left panel
illustrates the main coronary arteries: RCA, LCA splitting into the
LAD and LCx arteries and their branches including the PDA, RMA and
D1, D2. The right panel categorizes the coronary vessels into
epicardial arteries (>400 µm), pre-arterioles (100-400
µm), arterioles (40-100 µm) and capillaries (<10
µm), each crucial for different aspects of myocardial
perfusion, from conduit functions to metabolic regulation and
nutrient exchange. RCA, right coronary artery; LCA, left coronary
artery; LAD, left anterior descending; LCx, left circumflex; PDA,
posterior descending artery; RMA, right marginal artery.

Figure 2

Pathological mechanisms of IHD. The
top right section outlines the stages of atherosclerosis: initial
plaque formation, growth, rupture and subsequent thrombus
development limiting blood flow. The bottom right section addresses
vascular dysfunction, showing vasodilatory dysfunction and enhanced
vasoconstriction that further impair coronary circulation and lead
to myocardial ischemia. IHD, ischemic heart disease.

Figure 3

Various neurostimulation techniques
in IHD. 1) Brain stimulation, where devices apply electrical
impulses directly to the brain. 2) Transcutaneous auricular vagus
nerve stimulation, targeting the ear's auricular branch of the
vagus nerve for both direct autonomic effects and anti-inflammatory
benefits. 3) Cervical vagus nerve stimulation, which involves
direct stimulation of the cervical vagus nerve affecting both
afferent and efferent fibers to modulate autonomic function and
inflammation. 4) Spinal cord stimulation, where devices placed
along the spine modulate neurological signals to alleviate pain and
improve cardiovascular function. IHD, ischemic heart disease.
View References

1 

Ralapanawa U and Sivakanesan R: Epidemiology and the magnitude of coronary artery disease and acute coronary syndrome: A narrative review. J Epidemiol Glob Health. 11:169–177. 2021. View Article : Google Scholar : PubMed/NCBI

2 

Pagliaro BR, Cannata F, Stefanini GG and Bolognese L: Myocardial ischemia and coronary disease in heart failure. Heart Fail Rev. 25:53–65. 2020. View Article : Google Scholar

3 

Horowitz LN, Harken AH, Josephson ME and Kastor JA: Surgical treatment of ventricular arrhythmias in coronary artery disease. Ann Intern Med. 95:88–97. 1981. View Article : Google Scholar : PubMed/NCBI

4 

Sara JD, Eleid MF, Gulati R and Holmes DR Jr: Sudden cardiac death from the perspective of coronary artery disease. Mayo Clin Proc. 89:1685–1698. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Russell MW, Huse DM, Drowns S, Hamel EC and Hartz SC: Direct medical costs of coronary artery disease in the United States. Am J Cardiol. 81:1110–1115. 1998. View Article : Google Scholar : PubMed/NCBI

6 

Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A, Kahn J, Afonso L, Williams KA Sr and Flack JM: Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: A Mendelian randomization analysis. J Am Coll Cardiol. 60:2631–2639. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Toth PP: High-density lipoprotein and cardiovascular risk. Circulation. 109:1809–1812. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Gallo G, Volpe M and Savoia C: Endothelial dysfunction in hypertension: Current concepts and clinical implications. Front Med (Lausanne). 8:7989582022. View Article : Google Scholar : PubMed/NCBI

9 

Yang DR, Wang MY, Zhang CL and Wang Y: Endothelial dysfunction in vascular complications of diabetes: A comprehensive review of mechanisms and implications. Front Endocrinol (Lausanne). 15:13592552024. View Article : Google Scholar : PubMed/NCBI

10 

Alpert JS: New coronary heart disease risk factors. Am J Med. 136:331–332. 2023. View Article : Google Scholar

11 

Malakar AK, Choudhury D, Halder B, Paul P, Uddin A and Chakraborty S: A review on coronary artery disease, its risk factors, and therapeutics. J Cell Physiol. 234:16812–16823. 2019. View Article : Google Scholar : PubMed/NCBI

12 

Nettleship J, Jones R, Channer K and Jones T: Testosterone and coronary artery disease. Front Horm Res. 37:91–107. 2009. View Article : Google Scholar

13 

Bauersachs R, Zeymer U, Brière JB, Marre C, Bowrin K and Huelsebeck M: Burden of coronary artery disease and peripheral artery disease: A literature review. Cardiovasc Ther. 2019:82950542019. View Article : Google Scholar

14 

Lee YTH, Fang J, Schieb L, Park S, Casper M and Gillespie C: Prevalence and trends of coronary heart disease in the United States, 2011 to 2018. JAMA Cardiol. 7:459–462. 2022. View Article : Google Scholar : PubMed/NCBI

15 

Libby P and Theroux P: Pathophysiology of coronary artery disease. Circulation. 111:3481–3488. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Weber C and Noels H: Atherosclerosis: Current pathogenesis and therapeutic options. Nat Med. 17:1410–1422. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Attiq A, Afzal S, Ahmad W and Kandeel M: Hegemony of inflammation in atherosclerosis and coronary artery disease. Eur J Pharmacol. 966:1763382024. View Article : Google Scholar : PubMed/NCBI

18 

Chen Y, Yu Y, Zou W, Zhang M, Wang Y and Gu Y: Association between cardiac autonomic nervous dysfunction and the severity of coronary lesions in patients with stable coronary artery disease. J Int Med Res. 46:3729–3740. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Parisi AF, Folland ED and Hartigan P: A comparison of angioplasty with medical therapy in the treatment of single-vessel coronary artery disease. Veterans affairs ACME investigators. N Engl J Med. 326:10–16. 1992. View Article : Google Scholar : PubMed/NCBI

20 

Velazquez EJ, Lee KL, Jones RH, Al-Khalidi HR, Hill JA, Panza JA, Michler RE, Bonow RO, Doenst T, Petrie MC, et al: Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med. 374:1511–1520. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Del Buono MG, Montone RA, Camilli M, Carbone S, Narula J, Lavie CJ, Niccoli G and Crea F: Coronary microvascular dysfunction across the spectrum of cardiovascular diseases: JACC state-of-the-art review. J Am Coll Cardiol. 78:1352–1371. 2021. View Article : Google Scholar : PubMed/NCBI

22 

Silvani A, Calandra-Buonaura G, Dampney RAL and Cortelli P: Brain-heart interactions: Physiology and clinical implications. Philos Trans A Math Phys Eng Sci. 374:201501812016.PubMed/NCBI

23 

Wehrwein EA, Orer HS and Barman SM: Overview of the anatomy, physiology, and pharmacology of the autonomic nervous system. Compr Physiol. 6:1239–1278. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Silva LEV, Silva CAA, Salgado HC and Fazan R Jr: The role of sympathetic and vagal cardiac control on complexity of heart rate dynamics. Am J Physiol Heart Circ Physiol. 312:H469–H477. 2017. View Article : Google Scholar

25 

Charkoudian N and Rabbitts JA: Sympathetic neural mechanisms in human cardiovascular health and disease. Mayo Clin Proc. 84:822–830. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Kasahara Y, Yoshida C, Saito M and Kimura Y: Assessments of heart rate and sympathetic and parasympathetic nervous activities of normal mouse fetuses at different stages of fetal development using fetal electrocardiography. Front Physiol. 12:6528282021. View Article : Google Scholar : PubMed/NCBI

27 

Curtis BM and O'Keefe JH Jr: Autonomic tone as a cardiovascular risk factor: The dangers of chronic fight or flight. Mayo Clin Proc. 77:45–54. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Brunner-La Rocca HP, Esler MD, Jennings GL and Kaye DM: Effect of cardiac sympathetic nervous activity on mode of death in congestive heart failure. Eur Heart J. 22:1136–1143. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Hadaya J and Ardell JL: Autonomic modulation for cardiovascular disease. Front Physiol. 11:6174592020. View Article : Google Scholar

30 

Shen MJ and Zipes DP: Role of the autonomic nervous system in modulating cardiac arrhythmias. Circ Res. 114:1004–1021. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Malpas SC: Sympathetic nervous system overactivity and its role in the development of cardiovascular disease. Physiol Rev. 90:513–557. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Grassi G and Drager LF: Sympathetic overactivity, hypertension and cardiovascular disease: State of the art. Curr Med Res Opin. 40(Suppl 1): S5–S13. 2024. View Article : Google Scholar

33 

Bazoukis G, Stavrakis S and Armoundas AA: Vagus nerve stimulation and inflammation in cardiovascular disease: A state-of-the-art review. J Am Heart Assoc. 12:e0305392023. View Article : Google Scholar : PubMed/NCBI

34 

Capilupi MJ, Kerath SM and Becker LB: Vagus nerve stimulation and the cardiovascular system. Cold Spring Harb Perspect Med. 10:a0341732020. View Article : Google Scholar

35 

De Ferrari GM and Schwartz PJ: Vagus nerve stimulation: from pre-clinical to clinical application: Challenges and future directions. Heart Fail Rev. 16:195–203. 2011. View Article : Google Scholar

36 

Deer TR, Levy RM, Kramer J, Poree L, Amirdelfan K, Grigsby E, Staats P, Burton AW, Burgher AH, Obray J, et al: Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: A randomized comparative trial. Pain. 158:669–681. 2017. View Article : Google Scholar :

37 

Bernstein SA, Wong B, Vasquez C, Rosenberg SP, Rooke R, Kuznekoff LM, Lader JM, Mahoney VM, Budylin T, Älvstrand M, et al: Spinal cord stimulation protects against atrial fibrillation induced by tachypacing. Heart Rhythm. 9:1426–1433.e3. 2012. View Article : Google Scholar : PubMed/NCBI

38 

Torre-Amione G, Alo K, Estep JD, Valderrabano M, Khalil N, Farazi TG, Rosenberg SP, Ness L and Gill J: Spinal cord stimulation is safe and feasible in patients with advanced heart failure: Early clinical experience. Eur J Heart Fail. 16:788–795. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Cucinotta F, Swinnen B, Makovac E, Hirschbichler S, Pereira E, Little S, Morgante F and Ricciardi L: Short term cardiovascular symptoms improvement after deep brain stimulation in patients with Parkinson's disease: A systematic review. J Neurol. 271:3764–3776. 2024. View Article : Google Scholar : PubMed/NCBI

40 

Clancy JA, Johnson R, Raw R, Deuchars SA and Deuchars J: Anodal transcranial direct current stimulation (tDCS) over the motor cortex increases sympathetic nerve activity. Brain Stimul. 7:97–104. 2014. View Article : Google Scholar

41 

Lee H, Lee JH, Hwang MH and Kang N: Repetitive transcranial magnetic stimulation improves cardiovascular autonomic nervous system control: A meta-analysis. J Affect Disord. 339:443–453. 2023. View Article : Google Scholar : PubMed/NCBI

42 

De Decker K, Beese U, Staal MJ and Dejongste MJL: Electrical neuromodulation for patients with cardiac diseases. Neth Heart J. 21:91–94. 2013. View Article : Google Scholar :

43 

Zipes DP, Neuzil P, Theres H, Caraway D, Mann DL, Mannheimer C, Van Buren P, Linde C, Linderoth B, Kueffer F, et al: Determining the feasibility of spinal cord neuromodulation for the treatment of chronic systolic heart failure: The DEFEAT-HF study. JACC Heart Fail. 4:129–136. 2016. View Article : Google Scholar

44 

Rodrigues B, Barboza CA, Moura EG, Ministro G, Ferreira-Melo SE, Castaño JB, Nunes WMS, Mostarda C, Coca A, Vianna LC and Moreno-Junior H: Acute and short-term autonomic and hemodynamic responses to transcranial direct current stimulation in patients with resistant hypertension. Front Cardiovasc Med. 9:8534272022. View Article : Google Scholar : PubMed/NCBI

45 

Imran TF, Malapero R, Qavi AH, Hasan Z, de la Torre B, Patel YR, Yong RJ, Djousse L, Gaziano JM and Gerhard-Herman MD: Efficacy of spinal cord stimulation as an adjunct therapy for chronic refractory angina pectoris. Int J Cardiol. 227:535–542. 2017. View Article : Google Scholar

46 

Palasubramaniam J, Wang X and Peter K: Myocardial infarction-from atherosclerosis to thrombosis. Arterioscler Thromb Vasc Biol. 39:e176–e185. 2019. View Article : Google Scholar : PubMed/NCBI

47 

Libby P: Inflammation in atherosclerosis. Nature. 420:868–874. 2002. View Article : Google Scholar : PubMed/NCBI

48 

Bradley C and Berry C: Definition and epidemiology of coronary microvascular disease. J Nucl Cardiol. 29:1763–1775. 2022. View Article : Google Scholar : PubMed/NCBI

49 

Marinescu MA, Löffler AI, Ouellette M, Smith L, Kramer CM and Bourque JM: Coronary microvascular dysfunction, microvascular angina, and treatment strategies. JACC Cardiovasc Imaging. 8:210–220. 2015. View Article : Google Scholar : PubMed/NCBI

50 

Gutiérrez E, Flammer AJ, Lerman LO, Elízaga J, Lerman A and Fernández-Avilés F: Endothelial dysfunction over the course of coronary artery disease. Eur Heart J. 34:3175–3181. 2013. View Article : Google Scholar : PubMed/NCBI

51 

Bentzon JF, Otsuka F, Virmani R and Falk E: Mechanisms of plaque formation and rupture. Circ Res. 114:1852–1866. 2014. View Article : Google Scholar : PubMed/NCBI

52 

Villa AD, Sammut E, Nair A, Rajani R, Bonamini R and Chiribiri A: Coronary artery anomalies overview: The normal and the abnormal. World J Radiol. 8:537–555. 2016. View Article : Google Scholar : PubMed/NCBI

53 

Chen M, Wu X and Xu C: The 'hands' teaching method in coronary artery anatomy. Asian J Surg. 47:3183–3184. 2024. View Article : Google Scholar : PubMed/NCBI

54 

Chilian WM and Marcus ML: Phasic coronary blood flow velocity in intramural and epicardial coronary arteries. Circ Res. 50:775–781. 1982. View Article : Google Scholar : PubMed/NCBI

55 

De Bruyne B, Hersbach F, Pijls NH, Bartunek J, Bech JW, Heyndrickx GR, Gould KL and Wijns W: Abnormal epicardial coronary resistance in patients with diffuse atherosclerosis but 'normal' coronary angiography. Circulation. 104:2401–2406. 2001. View Article : Google Scholar : PubMed/NCBI

56 

Camici PG and Rimoldi OE: The clinical value of myocardial blood flow measurement. J Nucl Med. 50:1076–1087. 2009. View Article : Google Scholar : PubMed/NCBI

57 

Duncker DJ, Koller A, Merkus D and Canty JM Jr: Regulation of coronary blood flow in health and ischemic heart disease. Prog Cardiovasc Dis. 57:409–422. 2015. View Article : Google Scholar

58 

Dedkov EI, Christensen LP, Weiss RM and Tomanek RJ: Reduction of heart rate by chronic beta1-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart. Am J Physiol Heart Circ Physiol. 288:H2684–H2693. 2005. View Article : Google Scholar : PubMed/NCBI

59 

Pruthi S, Siddiqui E and Smilowitz NR: Beyond coronary artery disease: Assessing the microcirculation. Interv Cardiol Clin. 12:119–129. 2023.

60 

Palade GE: Blood capillaries of the heart and other organs. Circulation. 24:368–388. 1961. View Article : Google Scholar : PubMed/NCBI

61 

Wolff CB: Normal cardiac output, oxygen delivery and oxygen extraction. Adv Exp Med Biol. 599:169–182. 2007. View Article : Google Scholar : PubMed/NCBI

62 

Gandoy-Fieiras N, Gonzalez-Juanatey JR and Eiras S: Myocardium metabolism in physiological and pathophysiological states: Implications of epicardial adipose tissue and potential therapeutic targets. Int J Mol Sci. 21:26412020. View Article : Google Scholar : PubMed/NCBI

63 

Hollenberg M and Tager IB: Oxygen uptake efficiency slope: An index of exercise performance and cardiopulmonary reserve requiring only submaximal exercise. J Am Coll Cardiol. 36:194–201. 2000. View Article : Google Scholar : PubMed/NCBI

64 

Downey JM: Myocardial contractile force as a function of coronary blood flow. Am J Physiol. 230:1–6. 1976. View Article : Google Scholar : PubMed/NCBI

65 

Heusch G: Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: Benefit from selective bradycardic agents. Br J Pharmacol. 153:1589–1601. 2008. View Article : Google Scholar : PubMed/NCBI

66 

Seligman H, Nijjer SS, van de Hoef TP, de Waard GA, Mejía-Rentería H, Echavarria-Pinto M, Shun-Shin MJ, Howard JP, Cook CM, Warisawa T, et al: Phasic flow patterns of right versus left coronary arteries in patients undergoing clinical physiological assessment. EuroIntervention. 17:1260–1270. 2022. View Article : Google Scholar

67 

Comunale G, Peruzzo P, Castaldi B, Razzolini R, Di Salvo G, Padalino MA and Susin FM: Understanding and recognition of the right ventricular function and dysfunction via a numerical study. Sci Rep. 11:37092021. View Article : Google Scholar : PubMed/NCBI

68 

Nikorowitsch J, Bei der Kellen R, Haack A, Magnussen C, Prochaska J, Wild PS, Dörr M, Twerenbold R, Schnabel RB, Kirchhof P, et al: Correlation of systolic and diastolic blood pressure with echocardiographic phenotypes of cardiac structure and function from three German population-based studies. Sci Rep. 13:145252023. View Article : Google Scholar : PubMed/NCBI

69 

Yang HJ, Dey D, Sykes J, Klein M, Butler J, Kovacs MS, Sobczyk O, Sharif B, Bi X, Kali A, et al: Arterial CO2 as a potent coronary vasodilator: A preclinical PET/MR validation study with implications for cardiac stress testing. J Nucl Med. 58:953–960. 2017. View Article : Google Scholar : PubMed/NCBI

70 

Shryock JC, Snowdy S, Baraldi PG, Cacciari B, Spalluto G, Monopoli A, Ongini E, Baker SP and Belardinelli L: A2A-adenosine receptor reserve for coronary vasodilation. Circulation. 98:711–718. 1998. View Article : Google Scholar : PubMed/NCBI

71 

Mori K, Nakaya Y, Sakamoto S, Hayabuchi Y, Matsuoka S and Kuroda Y: Lactate-induced vascular relaxation in porcine coronary arteries is mediated by Ca2+-activated K+ channels. J Mol Cell Cardiol. 30:349–356. 1998. View Article : Google Scholar : PubMed/NCBI

72 

Tarnow J, Brückner JB, Eberlein HJ, Gethmann JW, Hess W, Patschke D and Wilde J: Blood pH and PaCO2 as chemical factors in myocardial blood flow control. Basic Res Cardiol. 70:685–696. 1975. View Article : Google Scholar : PubMed/NCBI

73 

Ishizaka H and Kuo L: Acidosis-induced coronary arteriolar dilation is mediated by ATP-sensitive potassium channels in vascular smooth muscle. Circ Res. 78:50–57. 1996. View Article : Google Scholar : PubMed/NCBI

74 

Knot HJ, Zimmermann PA and Nelson MT: Extracellular K(+)-induced hyperpolarizations and dilatations of rat coronary and cerebral arteries involve inward rectifier K(+) channels. J Physiol. 492:419–430. 1996. View Article : Google Scholar : PubMed/NCBI

75 

Dora KA, Borysova L, Ye X, Powell C, Beleznai TZ, Stanley CP, Bruno VD, Starborg T, Johnson E, Pielach A, et al: Human coronary microvascular contractile dysfunction associates with viable synthetic smooth muscle cells. Cardiovasc Res. 118:1978–1992. 2022. View Article : Google Scholar :

76 

Zhuge Y, Zhang J, Qian F, Wen Z, Niu C, Xu K, Ji H, Rong X, Chu M and Jia C: Role of smooth muscle cells in cardiovascular disease. Int J Biol Sci. 16:2741–2751. 2020. View Article : Google Scholar : PubMed/NCBI

77 

Young MA, Knight DR and Vatner SF: Autonomic control of large coronary arteries and resistance vessels. Prog Cardiovasc Dis. 30:211–234. 1987. View Article : Google Scholar : PubMed/NCBI

78 

Seddon M, Melikian N, Dworakowski R, Shabeeh H, Jiang B, Byrne J, Casadei B, Chowienczyk P and Shah AM: Effects of neuronal nitric oxide synthase on human coronary artery diameter and blood flow in vivo. Circulation. 119:2656–2662. 2009. View Article : Google Scholar : PubMed/NCBI

79 

Schrör K: Possible role of prostaglandins in the regulation of coronary blood flow. Basic Res Cardiol. 76:239–249. 1981. View Article : Google Scholar : PubMed/NCBI

80 

Dharmashankar K and Widlansky ME: Vascular endothelial function and hypertension: Insights and directions. Curr Hypertens Rep. 12:448–455. 2010. View Article : Google Scholar : PubMed/NCBI

81 

Lu Y, Cui X, Zhang L, Wang X, Xu Y, Qin Z, Liu G, Wang Q, Tian K, Lim KS, et al: The functional role of lipoproteins in atherosclerosis: Novel directions for diagnosis and targeting therapy. Aging Dis. 13:491–520. 2022. View Article : Google Scholar : PubMed/NCBI

82 

Kobayashi Y, Sakai C, Ishida T, Nagata M, Nakano Y and Ishida M: Mitochondrial DNA is a key driver in cigarette smoke extract-induced IL-6 expression. Hypertens Res. 47:88–101. 2024. View Article : Google Scholar

83 

Mundi S, Massaro M, Scoditti E, Carluccio MA, van Hinsbergh VWM, Iruela-Arispe ML and De Caterina R: Endothelial permeability, LDL deposition, and cardiovascular risk factors-a review. Cardiovasc Res. 114:35–52. 2018. View Article : Google Scholar

84 

Falk E: Pathogenesis of atherosclerosis. J Am Coll Cardiol. 47(8 Suppl): C7–C12. 2006. View Article : Google Scholar : PubMed/NCBI

85 

Aviram M: Macrophage foam cell formation during early atherogenesis is determined by the balance between pro-oxidants and anti-oxidants in arterial cells and blood lipoproteins. Antioxid Redox Signal. 1:585–594. 1999. View Article : Google Scholar

86 

Willemsen L and de Winther MP: Macrophage subsets in atherosclerosis as defined by single-cell technologies. J Pathol. 250:705–714. 2020. View Article : Google Scholar : PubMed/NCBI

87 

Newby AC and Zaltsman AB: Fibrous cap formation or destruction-the critical importance of vascular smooth muscle cell proliferation, migration and matrix formation. Cardiovasc Res. 41:345–360. 1999. View Article : Google Scholar : PubMed/NCBI

88 

Allahverdian S, Chehroudi AC, McManus BM, Abraham T and Francis GA: Contribution of intimal smooth muscle cells to cholesterol accumulation and macrophage-like cells in human atherosclerosis. Circulation. 129:1551–1559. 2014. View Article : Google Scholar : PubMed/NCBI

89 

Rong JX, Shapiro M, Trogan E and Fisher EA: Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading. Proc Natl Acad Sci USA. 100:13531–13536. 2003. View Article : Google Scholar : PubMed/NCBI

90 

Ajoolabady A, Pratico D, Lin L, Mantzoros CS, Bahijri S, Tuomilehto J and Ren J: Inflammation in atherosclerosis: Pathophysiology and mechanisms. Cell Death Dis. 15:8172024. View Article : Google Scholar : PubMed/NCBI

91 

Song B, Bie Y, Feng H, Xie B, Liu M and Zhao F: Inflammatory factors driving atherosclerotic plaque progression new insights. J Transl Int Med. 10:36–47. 2022. View Article : Google Scholar : PubMed/NCBI

92 

Francisco J and Del Re DP: Inflammation in myocardial ischemia/reperfusion injury: Underlying mechanisms and therapeutic potential. Antioxidants (Basel). 12:19442023. View Article : Google Scholar : PubMed/NCBI

93 

Bennett MR, Sinha S and Owens GK: Vascular smooth muscle cells in atherosclerosis. Circ Res. 118:692–702. 2016. View Article : Google Scholar : PubMed/NCBI

94 

Otsuka F, Kramer MCA, Woudstra P, Yahagi K, Ladich E, Finn AV, de Winter RJ, Kolodgie FD, Wight TN, Davis HR, et al: Natural progression of atherosclerosis from pathologic intimal thickening to late fibroatheroma in human coronary arteries: A pathology study. Atherosclerosis. 241:772–782. 2015. View Article : Google Scholar : PubMed/NCBI

95 

Badimon L and Vilahur G: Thrombosis formation on atherosclerotic lesions and plaque rupture. J Intern Med. 276:618–632. 2014. View Article : Google Scholar : PubMed/NCBI

96 

Kumar A, Kar S and Fay WP: Thrombosis, physical activity, and acute coronary syndromes. J Appl Physiol (1985). 111:599–605. 2011. View Article : Google Scholar : PubMed/NCBI

97 

Ha EJ, Kim Y, Cheung JY and Shim SS: Coronary artery disease in asymptomatic young adults: Its prevalence according to coronary artery disease risk stratification and the CT characteristics. Korean J Radiol. 11:425–432. 2010. View Article : Google Scholar : PubMed/NCBI

98 

Dzaye O, Razavi AC, Blaha MJ and Mortensen MB: Evaluation of coronary stenosis versus plaque burden for atherosclerotic cardiovascular disease risk assessment and management. Curr Opin Cardiol. 36:769–775. 2021. View Article : Google Scholar : PubMed/NCBI

99 

Kragel AH, Reddy SG, Wittes JT and Roberts WC: Morphometric analysis of the composition of atherosclerotic plaques in the four major epicardial coronary arteries in acute myocardial infarction and in sudden coronary death. Circulation. 80:1747–1756. 1989. View Article : Google Scholar : PubMed/NCBI

100 

Servoss SJ, Januzzi JL and Muller JE: Triggers of acute coronary syndromes. Prog Cardiovasc Dis. 44:369–380. 2002. View Article : Google Scholar : PubMed/NCBI

101 

Burke AP, Kolodgie FD, Farb A, Weber DK, Malcom GT, Smialek J and Virmani R: Healed plaque ruptures and sudden coronary death: Evidence that subclinical rupture has a role in plaque progression. Circulation. 103:934–940. 2001. View Article : Google Scholar : PubMed/NCBI

102 

Amabile N and Veugeois A: Ruptured and healed atherosclerotic plaques: Breaking bad? EuroIntervention. 15:e742–e744. 2019. View Article : Google Scholar : PubMed/NCBI

103 

Rittersma SZH, van der Wal AC, Koch KT, Piek JJ, Henriques JP, Mulder KJ, Ploegmakers JP, Meesterman M and de Winter RJ: Plaque instability frequently occurs days or weeks before occlusive coronary thrombosis: A pathological thrombectomy study in primary percutaneous coronary intervention. Circulation. 111:1160–1165. 2005. View Article : Google Scholar : PubMed/NCBI

104 

Fernández-Ortiz A, Badimon JJ, Falk E, Fuster V, Meyer B, Mailhac A, Weng D, Shah PK and Badimon L: Characterization of the relative thrombogenicity of atherosclerotic plaque components: Implications for consequences of plaque rupture. J Am Coll Cardiol. 23:1562–1569. 1994. View Article : Google Scholar : PubMed/NCBI

105 

Silvain J, Collet JP, Nagaswami C, Beygui F, Edmondson KE, Bellemain-Appaix A, Cayla G, Pena A, Brugier D, Barthelemy O, et al: Composition of coronary thrombus in acute myocardial infarction. J Am Coll Cardiol. 57:1359–1367. 2011. View Article : Google Scholar : PubMed/NCBI

106 

Mohammed AQ, Abdu FA, Liu L, Yin G, Mareai RM, Mohammed AA, Xu Y and Che W: Coronary microvascular dysfunction and myocardial infarction with non-obstructive coronary arteries: Where do we stand? Eur J Intern Med. 117:8–20. 2023. View Article : Google Scholar : PubMed/NCBI

107 

Herrmann J, Kaski JC and Lerman A: Coronary microvascular dysfunction in the clinical setting: From mystery to reality. Eur Heart J. 33:2771–2782b. 2012. View Article : Google Scholar : PubMed/NCBI

108 

Sinha A, Rahman H and Perera D: Coronary microvascular disease: Current concepts of pathophysiology, diagnosis and management. Cardiovasc Endocrinol Metab. 10:22–30. 2021. View Article : Google Scholar : PubMed/NCBI

109 

Rezaeian P, Shufelt CL, Wei J, Pacheco C, Cook-Wiens G, Berman D, Tamarappoo B, Thomson LE, Nelson MD, Anderson RD, et al: Arterial stiffness assessment in coronary microvascular dysfunction and heart failure with preserved ejection fraction: An initial report from the WISE-CVD continuation study. Am Heart J Plus. 41:1003902024.PubMed/NCBI

110 

Singh A, Ashraf S, Irfan H, Venjhraj F, Verma A, Shaukat A, Tariq MD and Hamza HM: Heart failure and microvascular dysfunction: An in-depth review of mechanisms, diagnostic strategies, and innovative therapies. Ann Med Surg (Lond). 87:616–626. 2024. View Article : Google Scholar

111 

Li M, Qian M, Kyler K and Xu J: Endothelial-vascular smooth muscle cells interactions in atherosclerosis. Front Cardiovasc Med. 5:1512018. View Article : Google Scholar : PubMed/NCBI

112 

Medina-Leyte DJ, Zepeda-García O, Domínguez-Pérez M, González-Garrido A, Villarreal-Molina T and Jacobo-Albavera L: Endothelial dysfunction, inflammation and coronary artery disease: potential biomarkers and promising therapeutical approaches. Int J Mol Sci. 22:38502021. View Article : Google Scholar : PubMed/NCBI

113 

Fleissner F and Thum T: Critical role of the nitric oxide/reactive oxygen species balance in endothelial progenitor dysfunction. Antioxid Redox Signal. 15:933–948. 2011. View Article : Google Scholar :

114 

Goodwill AG, Dick GM, Kiel AM and Tune JD: Regulation of coronary blood flow. Compr Physiol. 7:321–382. 2017. View Article : Google Scholar : PubMed/NCBI

115 

Maddox TM, Stanislawski MA, Grunwald GK, Bradley SM, Ho PM, Tsai TT, Patel MR, Sandhu A, Valle J, Magid DJ, et al: Nonobstructive coronary artery disease and risk of myocardial infarction. JAMA. 312:1754–1763. 2014. View Article : Google Scholar : PubMed/NCBI

116 

Heusch G: Myocardial ischemia: Lack of coronary blood flow or myocardial oxygen supply/demand imbalance? Circ Res. 119:194–196. 2016. View Article : Google Scholar : PubMed/NCBI

117 

Pasupathy S, Tavella R and Beltrame JF: Myocardial infarction with nonobstructive coronary arteries (MINOCA): The past, present, and future management. Circulation. 135:1490–1493. 2017. View Article : Google Scholar : PubMed/NCBI

118 

Ford TJ, Rocchiccioli P, Good R, McEntegart M, Eteiba H, Watkins S, Shaukat A, Lindsay M, Robertson K, Hood S, et al: Systemic microvascular dysfunction in microvascular and vasospastic angina. Eur Heart J. 39:4086–4097. 2018. View Article : Google Scholar : PubMed/NCBI

119 

Mohri M, Koyanagi M, Egashira K, Tagawa H, Ichiki T, Shimokawa H and Takeshita A: Angina pectoris caused by coronary microvascular spasm. Lancet. 351:1165–1169. 1998. View Article : Google Scholar : PubMed/NCBI

120 

Mehta PK, Thobani A and Vaccarino V: Coronary artery spasm, coronary reactivity, and their psychological context. Psychosom Med. 81:233–236. 2019. View Article : Google Scholar : PubMed/NCBI

121 

Hung MJ, Hu P and Hung MY: Coronary artery spasm: Review and update. Int J Med Sci. 11:1161–1171. 2014. View Article : Google Scholar : PubMed/NCBI

122 

Igarashi Y, Yamazoe M and Shibata A: Effect of direct intracoronary administration of methylergonovine in patients with and without variant angina. Am Heart J. 121:1094–1100. 1991. View Article : Google Scholar : PubMed/NCBI

123 

Frantz RP, Lerman A, Edwards BS, Olson LJ, Higano ST, Schwartz RS, Daly RC, McGregor CG and Rodeheffer RJ: Methylergonovine-induced diffuse coronary spasm in a patient with exercise-induced coronary spasm after heart transplantation. J Heart Lung Transplant. 13:834–839. 1994.PubMed/NCBI

124 

Doenst T, Thiele H, Haasenritter J, Wahlers T, Massberg S and Haverich A: The treatment of coronary artery disease. Dtsch Arztebl Int. 119:716–723. 2022.PubMed/NCBI

125 

Hennekens CH: Aspirin in the treatment and prevention of cardiovascular disease. Annu Rev Public Health. 18:37–49. 1997. View Article : Google Scholar : PubMed/NCBI

126 

Sabatine MS, Wiviott SD, Im K, Murphy SA and Giugliano RP: Efficacy and safety of further lowering of low-density lipoprotein cholesterol in patients starting with very low levels: A meta-analysis. JAMA Cardiol. 3:823–828. 2018. View Article : Google Scholar : PubMed/NCBI

127 

Manikandan A, Moharil P, Sathishkumar M, Muñoz-Garay C and Sivakumar A: Therapeutic investigations of novel indoxyl-based indolines: A drug target validation and structure-activity relationship of angiotensin-converting enzyme inhibitors with cardiovascular regulation and thrombolytic potential. Eur J Med Chem. 141:417–426. 2017. View Article : Google Scholar : PubMed/NCBI

128 

Godoy LC, Farkouh ME, Austin PC, Shah BR, Qiu F, Jackevicius CA, Wijeysundera HC, Krumholz HM and Ko DT: Association of beta-blocker therapy with cardiovascular outcomes in patients with stable ischemic heart disease. J Am Coll Cardiol. 81:2299–2311. 2023. View Article : Google Scholar : PubMed/NCBI

129 

Yan Y, An W, Mei S, Zhu Q, Li C, Yang L, Zhao Z and Huo J: Real-world research on beta-blocker usage trends in China and safety exploration based on the FDA adverse event reporting system (FAERS). BMC Pharmacol Toxicol. 25:862024. View Article : Google Scholar : PubMed/NCBI

130 

Elliott WJ and Ram CVS: Calcium channel blockers. J Clin Hypertens (Greenwich). 13:687–689. 2011. View Article : Google Scholar : PubMed/NCBI

131 

Kalinowski L, Dobrucki LW, Szczepanska-Konkel M, Jankowski M, Martyniec L, Angielski S and Malinski T: Third-generation beta-blockers stimulate nitric oxide release from endothelial cells through ATP efflux: A novel mechanism for antihypertensive action. Circulation. 107:2747–2752. 2003. View Article : Google Scholar : PubMed/NCBI

132 

Lawton JS, Tamis-Holland JE, Bangalore S, Bates ER, Beckie TM, Bischoff JM, Bittl JA, Cohen MG, DiMaio JM, Don CW, et al: 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: Executive summary: A report of the American college of cardiology/american heart association joint committee on clinical practice guidelines. Circulation. 145:e4–e17. 2022.

133 

Head SJ, Kieser TM, Falk V, Huysmans HA and Kappetein AP: Coronary artery bypass grafting: Part 1-the evolution over the first 50 years. Eur Heart J. 34:2862–2872. 2013. View Article : Google Scholar : PubMed/NCBI

134 

Costa MACD, Betero AL, Okamoto J, Schafranski M, Reis ESD and Gomes RZ: Coronary endarterectomy: A case control study and evaluation of early patency rate of endarterectomized arteries. Braz J Cardiovasc Surg. 35:9–15. 2020.PubMed/NCBI

135 

González-Montero J, Brito R, Gajardo AI and Rodrigo R: Myocardial reperfusion injury and oxidative stress: Therapeutic opportunities. World J Cardiol. 10:74–86. 2018. View Article : Google Scholar : PubMed/NCBI

136 

Hausenloy DJ and Yellon DM: Myocardial ischemia-reperfusion injury: A neglected therapeutic target. J Clin Invest. 123:92–100. 2013. View Article : Google Scholar : PubMed/NCBI

137 

McBride W, Lange RA and Hillis LD: Restenosis after successful coronary angioplasty. Pathophysiology and prevention. N Engl J Med. 318:1734–1737. 1988. View Article : Google Scholar : PubMed/NCBI

138 

Smart NA, Dieberg G and King N: Long-term outcomes of on-versus off-pump coronary artery bypass grafting. J Am Coll Cardiol. 71:983–991. 2018. View Article : Google Scholar : PubMed/NCBI

139 

Camici PG and Crea F: Coronary microvascular dysfunction. N Engl J Med. 356:830–840. 2007. View Article : Google Scholar : PubMed/NCBI

140 

Roffi M, Meier B and Gallino A: Fifty years of percutaneous transluminal angioplasty. Eur Heart J. 45:1779–1780. 2024. View Article : Google Scholar : PubMed/NCBI

141 

Ruel M and Chikwe J: Coronary artery bypass grafting: Past and future. Circulation. 150:1067–1069. 2024. View Article : Google Scholar : PubMed/NCBI

142 

Rocco E, Grimaldi MC, Maino A, Cappannoli L, Pedicino D, Liuzzo G and Biasucci LM: Advances and challenges in biomarkers use for coronary microvascular dysfunction: From bench to clinical practice. J Clin Med. 11:20552022. View Article : Google Scholar : PubMed/NCBI

143 

Soleymani M, Masoudkabir F, Shabani M, Vasheghani-Farahani A, Behnoush AH and Khalaji A: Updates on pharmacologic management of microvascular angina. Cardiovasc Ther. 2022:60802582022. View Article : Google Scholar : PubMed/NCBI

144 

Yang L, Zhao W, Kan Y, Ren C and Ji X: From mechanisms to medicine: Neurovascular coupling in the diagnosis and treatment of cerebrovascular disorders: A narrative review. Cells. 14:162024. View Article : Google Scholar

145 

Bairey Merz CN, Pepine CJ, Shimokawa H and Berry C: Treatment of coronary microvascular dysfunction. Cardiovasc Res. 116:856–870. 2020. View Article : Google Scholar : PubMed/NCBI

146 

Fatima M, Bazarbaev A, Rana A, Khurshid R, Effiom V, Bajwa NK, Nasir A, Candelario K, Tabraiz SA, Colon S, et al: Neuroprotective strategies in coronary artery disease interventions. J Cardiovasc Dev Dis. 12:1432025.PubMed/NCBI

147 

Manolis AA, Manolis TA, Apostolopoulos EJ, Apostolaki NE, Melita H and Manolis AS: The role of the autonomic nervous system in cardiac arrhythmias: The neuro-cardiac axis, more foe than friend? Trends Cardiovasc Med. 31:290–302. 2021. View Article : Google Scholar

148 

Armour JA: Functional anatomy of intrathoracic neurons innervating the atria and ventricles. Heart Rhythm. 7:994–996. 2010. View Article : Google Scholar : PubMed/NCBI

149 

Brodde OE, Bruck H, Leineweber K and Seyfarth T: Presence, distribution and physiological function of adrenergic and muscarinic receptor subtypes in the human heart. Basic Res Cardiol. 96:528–538. 2001. View Article : Google Scholar

150 

Kawashima T: The autonomic nervous system of the human heart with special reference to its origin, course, and peripheral distribution. Anat Embryol (Berl). 209:425–438. 2005. View Article : Google Scholar : PubMed/NCBI

151 

Burnstock G: Autonomic neurotransmission: 60 Years since sir henry dale. Annu Rev Pharmacol Toxicol. 49:1–30. 2009. View Article : Google Scholar

152 

Nikolaidis LA, Trumble D, Hentosz T, Doverspike A, Huerbin R, Mathier MA, Shen YT and Shannon RP: Catecholamines restore myocardial contractility in dilated cardiomyopathy at the expense of increased coronary blood flow and myocardial oxygen consumption (MvO2 cost of catecholamines in heart failure). Eur J Heart Fail. 6:409–419. 2004. View Article : Google Scholar : PubMed/NCBI

153 

Rajendran PS, Challis RC, Fowlkes CC, Hanna P, Tompkins JD, Jordan MC, Hiyari S, Gabris-Weber BA, Greenbaum A, Chan KY, et al: Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies. Nat Commun. 10:19442019. View Article : Google Scholar : PubMed/NCBI

154 

Machhada A, Hosford PS, Dyson A, Ackland GL, Mastitskaya S and Gourine AV: Optogenetic stimulation of vagal efferent activity preserves left ventricular function in experimental heart failure. JACC Basic Transl Sci. 5:799–810. 2020. View Article : Google Scholar : PubMed/NCBI

155 

Finlay M, Harmer SC and Tinker A: The control of cardiac ventricular excitability by autonomic pathways. Pharmacol Ther. 174:97–111. 2017. View Article : Google Scholar : PubMed/NCBI

156 

Kawano H, Okada R and Yano K: Histological study on the distribution of autonomic nerves in the human heart. Heart Vessels. 18:32–39. 2003. View Article : Google Scholar : PubMed/NCBI

157 

Liu X, Yu Y, Zhang H, Zhang M and Liu Y: The role of muscarinic acetylcholine receptor M3 in cardiovascular diseases. Int J Mol Sci. 25:75602024. View Article : Google Scholar

158 

Giannino G, Braia V, Griffith Brookles C, Giacobbe F, D'Ascenzo F, Angelini F, Saglietto A, De Ferrari GM and Dusi V: The intrinsic cardiac nervous system: From pathophysiology to therapeutic implications. Biology (Basel). 13:1052024.PubMed/NCBI

159 

Armour JA, Murphy DA, Yuan BX, Macdonald S and Hopkins DA: Gross and microscopic anatomy of the human intrinsic cardiac nervous system. Anat Rec. 247:289–298. 1997. View Article : Google Scholar : PubMed/NCBI

160 

Wake E and Brack K: Characterization of the intrinsic cardiac nervous system. Auton Neurosci. 199:3–16. 2016. View Article : Google Scholar : PubMed/NCBI

161 

Fedele L and Brand T: The intrinsic cardiac nervous system and its role in cardiac pacemaking and conduction. J Cardiovasc Dev Dis. 7:542020.PubMed/NCBI

162 

Rysevaite K, Saburkina I, Pauziene N, Noujaim SF, Jalife J and Pauza DH: Morphologic pattern of the intrinsic ganglionated nerve plexus in mouse heart. Heart Rhythm. 8:448–454. 2011. View Article : Google Scholar

163 

Kimura K, Ieda M and Fukuda K: Development, maturation, and transdifferentiation of cardiac sympathetic nerves. Circ Res. 110:325–336. 2012. View Article : Google Scholar : PubMed/NCBI

164 

Rajendran PS, Nakamura K, Ajijola OA, Vaseghi M, Armour JA, Ardell JL and Shivkumar K: Myocardial infarction induces structural and functional remodelling of the intrinsic cardiac nervous system. J Physiol. 594:321–341. 2016. View Article : Google Scholar :

165 

Gardner RT, Ripplinger CM, Myles RC and Habecker BA: Molecular mechanisms of sympathetic remodeling and arrhythmias. Circ Arrhythm Electrophysiol. 9:e0013592016. View Article : Google Scholar : PubMed/NCBI

166 

Hopkins DA, Macdonald SE, Murphy DA and Armour JA: Pathology of intrinsic cardiac neurons from ischemic human hearts. Anat Rec. 259:424–436. 2000. View Article : Google Scholar : PubMed/NCBI

167 

Hardwick JC, Ryan SE, Beaumont E, Ardell JL and Southerland EM: Dynamic remodeling of the guinea pig intrinsic cardiac plexus induced by chronic myocardial infarction. Auton Neurosci. 181:4–12. 2014. View Article : Google Scholar :

168 

Vaseghi M, Salavatian S, Rajendran PS, Yagishita D, Woodward WR, Hamon D, Yamakawa K, Irie T, Habecker BA and Shivkumar K: Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction. JCI Insight. 2:e867152017. View Article : Google Scholar : PubMed/NCBI

169 

Yperzeele L, van Hooff RJ, Nagels G, De Smedt A, De Keyser J and Brouns R: Heart rate variability and baroreceptor sensitivity in acute stroke: A systematic review. Int J Stroke. 10:796–800. 2015. View Article : Google Scholar : PubMed/NCBI

170 

Grilletti JVF, Scapini KB, Bernardes N, Spadari J, Bigongiari A, Mazuchi FAES, Caperuto EC, Sanches IC, Rodrigues B and De Angelis K: Impaired baroreflex sensitivity and increased systolic blood pressure variability in chronic post-ischemic stroke. Clinics (Sao Paulo). 73:e2532018. View Article : Google Scholar : PubMed/NCBI

171 

Chen Z, Venkat P, Seyfried D, Chopp M, Yan T and Chen J: Brain-heart interaction: Cardiac complications after stroke. Circ Res. 121:451–468. 2017. View Article : Google Scholar : PubMed/NCBI

172 

Tang S, Xiong L, Fan Y, Mok VCT, Wong KS and Leung TW: Stroke outcome prediction by blood pressure variability, heart rate variability, and baroreflex sensitivity. Stroke. 51:1317–1320. 2020. View Article : Google Scholar : PubMed/NCBI

173 

Aftyka J, Staszewski J, Dębiec A, Pogoda-Wesołowska A and Żebrowski J: Heart rate variability as a predictor of stroke course, functional outcome, and medical complications: A systematic review. Front Physiol. 14:11151642023. View Article : Google Scholar : PubMed/NCBI

174 

Giunta S, Xia S, Pelliccioni G and Olivieri F: Autonomic nervous system imbalance during aging contributes to impair endogenous anti-inflammaging strategies. Geroscience. 46:113–127. 2024. View Article : Google Scholar :

175 

Bruno RM, Ghiadoni L, Seravalle G, Dell'oro R, Taddei S and Grassi G: Sympathetic regulation of vascular function in health and disease. Front Physiol. 3:2842012. View Article : Google Scholar : PubMed/NCBI

176 

Amiya E, Watanabe M and Komuro I: The relationship between vascular function and the autonomic nervous system. Ann Vasc Dis. 7:109–119. 2014. View Article : Google Scholar : PubMed/NCBI

177 

He Z: The control mechanisms of heart rate dynamics in a new heart rate nonlinear time series model. Sci Rep. 10:48142020. View Article : Google Scholar : PubMed/NCBI

178 

Valensi P: Autonomic nervous system activity changes in patients with hypertension and overweight: Role and therapeutic implications. Cardiovasc Diabetol. 20:1702021. View Article : Google Scholar : PubMed/NCBI

179 

Monahan KD, Feehan RP, Sinoway LI and Gao Z: Contribution of sympathetic activation to coronary vasodilatation during the cold pressor test in healthy men: Effect of ageing. J Physiol. 591:2937–2947. 2013. View Article : Google Scholar : PubMed/NCBI

180 

Hoffman JIE and Buckberg GD: The myocardial oxygen supply: Demand index revisited. J Am Heart Assoc. 3:e0002852014. View Article : Google Scholar

181 

Hartupee J and Mann DL: Neurohormonal activation in heart failure with reduced ejection fraction. Nat Rev Cardiol. 14:30–38. 2017. View Article : Google Scholar :

182 

Remme WJ: The sympathetic nervous system and ischaemic heart disease. Eur Heart J. 19(Suppl F): F62–F71. 1998.PubMed/NCBI

183 

Szczepanska-Sadowska E: Neuromodulation of cardiac ischemic pain: Role of the autonomic nervous system and vasopressin. J Integr Neurosci. 23:492024. View Article : Google Scholar : PubMed/NCBI

184 

Wu L, Tai Y, Hu S, Zhang M, Wang R, Zhou W, Tao J, Han Y, Wang Q and Wei W: Bidirectional role of β2-adrenergic receptor in autoimmune diseases. Front Pharmacol. 9:13132018. View Article : Google Scholar

185 

Grisanti LA, Perez DM and Porter JE: Modulation of immune cell function by α(1)-adrenergic receptor activation. Curr Top Membr. 67:113–138. 2011. View Article : Google Scholar

186 

Perez DM: α1-Adrenergic receptors: insights into potential therapeutic opportunities for COVID-19, heart failure, and Alzheimer's disease. Int J Mol Sci. 24:41882023. View Article : Google Scholar

187 

Kinugawa T, Kato M, Ogino K, Osaki S, Tomikura Y, Igawa O, Hisatome I and Shigemasa C: Interleukin-6 and tumor necrosis factor-alpha levels increase in response to maximal exercise in patients with chronic heart failure. Int J Cardiol. 87:83–90. 2003. View Article : Google Scholar

188 

Li M, Yao W, Li S and Xi J: Norepinephrine induces the expression of interleukin-6 via β-adrenoreceptor-NAD(P)H oxidase system-NF-κB dependent signal pathway in U937 macrophages. Biochem Biophys Res Commun. 460:1029–1034. 2015. View Article : Google Scholar : PubMed/NCBI

189 

Al-Sharea A, Lee MKS, Whillas A, Michell DL, Shihata WA, Nicholls AJ, Cooney OD, Kraakman MJ, Veiga CB, Jefferis AM, et al: Chronic sympathetic driven hypertension promotes atherosclerosis by enhancing hematopoiesis. Haematologica. 104:456–467. 2019. View Article : Google Scholar :

190 

Stone PH, Libby P and Boden WE: Fundamental pathobiology of coronary atherosclerosis and clinical implications for chronic ischemic heart disease management-the plaque hypothesis: A narrative review. JAMA Cardiol. 8:192–201. 2023. View Article : Google Scholar

191 

Wang Y, Anesi J, Maier MC, Myers MA, Oqueli E, Sobey CG, Drummond GR and Denton KM: Sympathetic nervous system and atherosclerosis. Int J Mol Sci. 24:131322023. View Article : Google Scholar : PubMed/NCBI

192 

Chen YC, Smith M, Ying YL, Makridakis M, Noonan J, Kanellakis P, Rai A, Salim A, Murphy A, Bobik A, et al: Quantitative proteomic landscape of unstable atherosclerosis identifies molecular signatures and therapeutic targets for plaque stabilization. Commun Biol. 6:2652023. View Article : Google Scholar : PubMed/NCBI

193 

Apolloni S and D'Ambrosi N: Inflammation in the CNS and PNS: From molecular basis to therapy. Int J Mol Sci. 24:94172023. View Article : Google Scholar : PubMed/NCBI

194 

Zanos S: Closed-loop neuromodulation in physiological and translational research. Cold Spring Harb Perspect Med. 9:a0343142019. View Article : Google Scholar

195 

Ali R and Schwalb JM: History and future of spinal cord stimulation. Neurosurgery. 94:20–28. 2024.

196 

Ferraro MC, Gibson W, Rice ASC, Vase L, Coyle D and O'Connell NE: Spinal cord stimulation for chronic pain. Lancet Neurol. 21:4052022. View Article : Google Scholar : PubMed/NCBI

197 

Augustinsson LE, Linderoth B, Mannheimer C and Eliasson T: Spinal cord stimulation in cardiovascular disease. Neurosurg Clin N Am. 6:157–165. 1995. View Article : Google Scholar : PubMed/NCBI

198 

Theofilis P, Oikonomou E, Sagris M, Papageorgiou N, Tsioufis K and Tousoulis D: Novel concepts in the management of angina in coronary artery disease. Curr Pharm Des. 29:1825–1834. 2023. View Article : Google Scholar : PubMed/NCBI

199 

Greco S, Auriti A, Fiume D, Gazzeri G, Gentilucci G, Antonini L and Santini M: Spinal cord stimulation for the treatment of refractory angina pectoris: A two-year follow-up. Pacing Clin Electrophysiol. 22:26–32. 1999. View Article : Google Scholar : PubMed/NCBI

200 

Jessurun GA, DeJongste MJ, Hautvast RW, Tio RA, Brouwer J, van Lelieveld S and Crijns HJ: Clinical follow-up after cessation of chronic electrical neuromodulation in patients with severe coronary artery disease: A prospective randomized controlled study on putative involvement of sympathetic activity. Pacing Clin Electrophysiol. 22:1432–1439. 1999. View Article : Google Scholar : PubMed/NCBI

201 

Eddicks S, Maier-Hauff K, Schenk M, Müller A, Baumann G and Theres H: Thoracic spinal cord stimulation improves functional status and relieves symptoms in patients with refractory angina pectoris: The first placebo-controlled randomised study. Heart. 93:585–590. 2007. View Article : Google Scholar : PubMed/NCBI

202 

de Jongste MJ, Hautvast RW, Hillege HL and Lie KI: Efficacy of spinal cord stimulation as adjuvant therapy for intractable angina pectoris: A prospective, randomized clinical study. Working group on neurocardiology. J Am Coll Cardiol. 23:1592–1597. 1994. View Article : Google Scholar : PubMed/NCBI

203 

Hautvast RW, Blanksma PK, DeJongste MJ, Pruim J, van der Wall EE, Vaalburg W and Lie KI: Effect of spinal cord stimulation on myocardial blood flow assessed by positron emission tomography in patients with refractory angina pectoris. Am J Cardiol. 77:462–467. 1996. View Article : Google Scholar : PubMed/NCBI

204 

Hautvast RW, DeJongste MJ, Staal MJ, van Gilst WH and Lie KI: Spinal cord stimulation in chronic intractable angina pectoris: A randomized, controlled efficacy study. Am Heart J. 136:1114–1120. 1998. View Article : Google Scholar : PubMed/NCBI

205 

Vulink NC, Overgaauw DM, Jessurun GA, Tenvaarwerk IA, Kropmans TJ, van der Schans CP, Middel B, Staal MJ and Dejongste MJ: The effects of spinal cord stimulation on quality of life in patients with therapeutically chronic refractory angina pectoris. Neuromodulation. 2:33–40. 1999. View Article : Google Scholar : PubMed/NCBI

206 

McNab D, Khan SN, Sharples LD, Ryan JY, Freeman C, Caine N, Tait S, Hardy I and Schofield PM: An open label, single-centre, randomized trial of spinal cord stimulation vs percutaneous myocardial laser revascularization in patients with refractory angina pectoris: The SPiRiT trial. Eur Heart J. 27:1048–1053. 2006. View Article : Google Scholar : PubMed/NCBI

207 

Dyer MT, Goldsmith KA, Khan SN, Sharples LD, Freeman C, Hardy I, Buxton MJ and Schofield PM: Clinical and cost-effectiveness analysis of an open label, single-centre, randomised trial of spinal cord stimulation (SCS) versus percutaneous myocardial laser revascularisation (PMR) in patients with refractory angina pectoris: The SPiRiT trial. Trials. 9:402008. View Article : Google Scholar : PubMed/NCBI

208 

Bondesson S, Pettersson T, Erdling A, Hallberg IR, Wackenfors A and Edvinsson L: Comparison of patients undergoing enhanced external counterpulsation and spinal cord stimulation for refractory angina pectoris. Coron Artery Dis. 19:627–634. 2008. View Article : Google Scholar : PubMed/NCBI

209 

Andréll P, Yu W, Gersbach P, Gillberg L, Pehrsson K, Hardy I, Ståhle A, Andersen C and Mannheimer C: Long-term effects of spinal cord stimulation on angina symptoms and quality of life in patients with refractory angina pectoris-results from the European angina registry link study (EARL). Heart. 96:1132–1136. 2010. View Article : Google Scholar

210 

Lanza GA, Grimaldi R, Greco S, Ghio S, Sarullo F, Zuin G, De Luca A, Allegri M, Di Pede F, Castagno D, et al: Spinal cord stimulation for the treatment of refractory angina pectoris: A multicenter randomized single-blind study (the SCS-ITA trial). Pain. 152:45–52. 2011. View Article : Google Scholar

211 

Saraste A, Ukkonen H, Varis A, Vasankari T, Tunturi S, Taittonen M, Rautakorpi P, Luotolahti M, Airaksinen KE and Knuuti J: Effect of spinal cord stimulation on myocardial perfusion reserve in patients with refractory angina pectoris. Eur Heart J Cardiovasc Imaging. 16:449–455. 2015. View Article : Google Scholar

212 

Latif OA, Nedeljkovic SS and Stevenson LW: Spinal cord stimulation for chronic intractable angina pectoris: A unified theory on its mechanism. Clin Cardiol. 24:533–541. 2001. View Article : Google Scholar : PubMed/NCBI

213 

Southerland EM, Milhorn DM, Foreman RD, Linderoth B, DeJongste MJ, Armour JA, Subramanian V, Singh M, Singh K and Ardell JL: Preemptive, but not reactive, spinal cord stimulation mitigates transient ischemia-induced myocardial infarction via cardiac adrenergic neurons. Am J Physiol Heart Circ Physio. 292:H311–H327. 2007. View Article : Google Scholar

214 

Dale EA, Kipke J, Kubo Y, Sunshine MD, Castro PA, Ardell JL and Mahajan A: Spinal cord neural network interactions: Implications for sympathetic control of the porcine heart. Am J Physiol Heart Circ Physiol. 318:H830–H839. 2020. View Article : Google Scholar : PubMed/NCBI

215 

Salavatian S, Kuwabara Y, Wong B, Fritz JR, Howard-Quijano K, Foreman RD, Armour JA, Ardell JL and Mahajan A: Spinal neuromodulation mitigates myocardial ischemia-induced sympathoexcitation by suppressing the intermediolateral nucleus hyperactivity and spinal neural synchrony. Front Neurosci. 17:11802942023. View Article : Google Scholar : PubMed/NCBI

216 

Saddic LA, Howard-Quijano K, Kipke J, Kubo Y, Dale EA, Hoover D, Shivkumar K, Eghbali M and Mahajan A: Progression of myocardial ischemia leads to unique changes in immediate-early gene expression in the spinal cord dorsal horn. Am J Physiol Heart Circ Physiol. 315:H1592–H1601. 2018. View Article : Google Scholar : PubMed/NCBI

217 

Minisi AJ and Thames MD: Activation of cardiac sympathetic afferents during coronary occlusion. Evidence for reflex activation of sympathetic nervous system during transmural myocardial ischemia in the dog. Circulation. 84:357–367. 1991. View Article : Google Scholar : PubMed/NCBI

218 

Ajijola OA and Shivkumar K: Neural remodeling and myocardial infarction: The stellate ganglion as a double agent. J Am Coll Cardiol. 59:962–964. 2012. View Article : Google Scholar : PubMed/NCBI

219 

Ding X, Ardell JL, Hua F, McAuley RJ, Sutherly K, Daniel JJ and Williams CA: Modulation of cardiac ischemia-sensitive afferent neuron signaling by preemptive C2 spinal cord stimulation: Effect on substance P release from rat spinal cord. Am J Physiol Regul Integr Comp Physiol. 294:R93–R101. 2008. View Article : Google Scholar

220 

Law M, Sachdeva R, Darrow D and Krassioukov A: Cardiovascular effects of spinal cord stimulation: The highs, the lows, and the don't knows. Neuromodulation. 27:1164–1176. 2024. View Article : Google Scholar

221 

Tse HF, Turner S, Sanders P, Okuyama Y, Fujiu K, Cheung CW, Russo M, Green MDS, Yiu KH, Chen P, et al: Thoracic spinal cord stimulation for heart failure as a restorative treatment (SCS HEART study): First-in-man experience. Heart Rhythm. 12:588–595. 2015. View Article : Google Scholar

222 

Wu M, Linderoth B and Foreman RD: Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: A review of experimental studies. Auton Neurosci. 138:9–23. 2008. View Article : Google Scholar

223 

Gouveia FV, Warsi NM, Suresh H, Matin R and Ibrahim GM: Neurostimulation treatments for epilepsy: Deep brain stimulation, responsive neurostimulation and vagus nerve stimulation. Neurotherapeutics. 21:e003082024. View Article : Google Scholar : PubMed/NCBI

224 

Austelle CW, O'Leary GH, Thompson S, Gruber E, Kahn A, Manett AJ, Short B and Badran BW: A comprehensive review of vagus nerve stimulation for depression. Neuromodulation. 25:309–315. 2022. View Article : Google Scholar : PubMed/NCBI

225 

Gidron Y, Kupper N, Kwaijtaal M, Winter J and Denollet J: Vagus-brain communication in atherosclerosis-related inflammation: A neuroimmunomodulation perspective of CAD. Atherosclerosis. 195:e1–e9. 2007. View Article : Google Scholar

226 

Giordano F, Zicca A, Barba C, Guerrini R and Genitori L: Vagus nerve stimulation: Surgical technique of implantation and revision and related morbidity. Epilepsia. 58(Suppl 1): S85–S90. 2017. View Article : Google Scholar

227 

Winston GM, Guadix S, Lavieri MT, Uribe-Cardenas R, Kocharian G, Williams N, Sholle E, Grinspan Z and Hoffman CE: Closed-loop vagal nerve stimulation for intractable epilepsy: A single-center experience. Seizure. 88:95–101. 2021. View Article : Google Scholar : PubMed/NCBI

228 

Skarpaas TL and Morrell MJ: Intracranial stimulation therapy for epilepsy. Neurotherapeutics. 6:238–243. 2009. View Article : Google Scholar : PubMed/NCBI

229 

Sun FT and Morrell MJ: Closed-loop neurostimulation: The clinical experience. Neurotherapeutics. 11:553–563. 2014. View Article : Google Scholar : PubMed/NCBI

230 

Ottaviani MM, Vallone F, Micera S and Recchia FA: Closed-loop vagus nerve stimulation for the treatment of cardiovascular diseases: State of the art and future directions. Front Cardiovasc Med. 9:8669572022. View Article : Google Scholar : PubMed/NCBI

231 

Vilaine JP, Berdeaux A and Giudicelli JF: Effects of vagal stimulation on regional myocardial flows and ischemic injury in dogs. Eur J Pharmacol. 66:243–247. 1980. View Article : Google Scholar : PubMed/NCBI

232 

Zuanetti G, De Ferrari GM, Priori SG and Schwartz PJ: Protective effect of vagal stimulation on reperfusion arrhythmias in cats. Circ Res. 61:429–435. 1987. View Article : Google Scholar : PubMed/NCBI

233 

Rosenshtraukh L, Danilo P Jr, Anyukhovsky EP, Steinberg SF, Rybin V, Brittain-Valenti K, Molina-Viamonte V and Rosen MR: Mechanisms for vagal modulation of ventricular repolarization and of coronary occlusion-induced lethal arrhythmias in cats. Circ Res. 75:722–732. 1994. View Article : Google Scholar : PubMed/NCBI

234 

Ando M, Katare RG, Kakinuma Y, Zhang D, Yamasaki F, Muramoto K and Sato T: Efferent vagal nerve stimulation protects heart against ischemia-induced arrhythmias by preserving connexin43 protein. Circulation. 112:164–170. 2005. View Article : Google Scholar : PubMed/NCBI

235 

Uemura K, Li M, Tsutsumi T, Yamazaki T, Kawada T, Kamiya A, Inagaki M, Sunagawa K and Sugimachi M: Efferent vagal nerve stimulation induces tissue inhibitor of metalloproteinase-1 in myocardial ischemia-reperfusion injury in rabbit. Am J Physiol Heart Circ Physiol. 293:H2254–H2261. 2007. View Article : Google Scholar : PubMed/NCBI

236 

Del Rio CL, Dawson TA, Clymer BD, Paterson DJ and Billman GE: Effects of acute vagal nerve stimulation on the early passive electrical changes induced by myocardial ischaemia in dogs: Heart rate-mediated attenuation. Exp Physiol. 93:931–944. 2008. View Article : Google Scholar : PubMed/NCBI

237 

Beaumont E, Southerland EM, Hardwick JC, Wright GL, Ryan S, Li Y, KenKnight BH, Armour JA and Ardell JL: Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction. Am J Physiol Heart Circ Physiol. 309:H1198–H1206. 2015. View Article : Google Scholar : PubMed/NCBI

238 

Zamotrinsky A, Afanasiev S, Karpov RS and Cherniavsky A: Effects of electrostimulation of the vagus afferent endings in patients with coronary artery disease. Coron Artery Dis. 8:551–557. 1997.PubMed/NCBI

239 

Zamotrinsky AV, Kondratiev B and de Jong JW: Vagal neurostimulation in patients with coronary artery disease. Auton Neurosci. 88:109–116. 2001. View Article : Google Scholar : PubMed/NCBI

240 

Yu L, Huang B, Po SS, Tan T, Wang M, Zhou L, Meng G, Yuan S, Zhou X, Li X, et al: Low-level tragus stimulation for the treatment of ischemia and reperfusion injury in patients with ST-segment elevation myocardial infarction: A proof-of-concept study. JACC Cardiovasc Interv. 10:1511–1520. 2017. View Article : Google Scholar : PubMed/NCBI

241 

Bonaz B, Sinniger V and Pellissier S: Anti-inflammatory properties of the vagus nerve: Potential therapeutic implications of vagus nerve stimulation. J Physiol. 594:5781–5790. 2016. View Article : Google Scholar : PubMed/NCBI

242 

Li S, Qi D, Li JN, Deng XY and Wang DX: Vagus nerve stimulation enhances the cholinergic anti-inflammatory pathway to reduce lung injury in acute respiratory distress syndrome via STAT3. Cell Death Discovery. 7:632021. View Article : Google Scholar : PubMed/NCBI

243 

Hachuła M, Kosowski M, Basiak M and Okopień B: Influence of dulaglutide on serum biomarkers of atherosclerotic plaque instability: An interventional analysis of cytokine profiles in diabetic subjects-a pilot study. Medicina (Kaunas). 60:9082024. View Article : Google Scholar

244 

Shinlapawittayatorn K, Chinda K, Palee S, Surinkaew S, Thunsiri K, Weerateerangkul P, Chattipakorn S, KenKnight BH and Chattipakorn N: Low-amplitude, left vagus nerve stimulation significantly attenuates ventricular dysfunction and infarct size through prevention of mitochondrial dysfunction during acute ischemia-reperfusion injury. Heart Rhythm. 10:1700–1707. 2013. View Article : Google Scholar : PubMed/NCBI

245 

Lu Y, Chen K, Zhao W, Hua Y, Bao S, Zhang J, Wu T, Ge G, Yu Y, Sun J and Zhang F: Magnetic vagus nerve stimulation alleviates myocardial ischemia-reperfusion injury by the inhibition of pyroptosis through the M2AChR/OGDHL/ROS axis in rats. J Nanobiotechnology. 21:4212023. View Article : Google Scholar

246 

Luo B, Wu Y, Liu SL, Li XY, Zhu HR, Zhang L, Zheng F, Liu XY, Guo LY, Wang L, et al: Vagus nerve stimulation optimized cardiomyocyte phenotype, sarcomere organization and energy metabolism in infarcted heart through FoxO3A-VEGF signaling. Cell Death Dis. 11:9712020. View Article : Google Scholar : PubMed/NCBI

247 

Munhoz RP and Albuainain G: Deep brain stimulation: New programming algorithms and teleprogramming. Expert Rev Neurother. 23:467–478. 2023. View Article : Google Scholar : PubMed/NCBI

248 

Lee DJ, Lozano CS, Dallapiazza RF and Lozano AM: Current and future directions of deep brain stimulation for neurological and psychiatric disorders. J Neurosurg. 131:333–342. 2019. View Article : Google Scholar : PubMed/NCBI

249 

Basiago A and Binder DK: Effects of deep brain stimulation on autonomic function. Brain Sci. 6:332016. View Article : Google Scholar : PubMed/NCBI

250 

Fontes MAP, Dos Santos Machado LR, Viana ACR, Cruz MH, Nogueira ÍS, Oliveira MGL, Neves CB, Godoy ACV, Henderson LA and Macefield VG: The insular cortex, autonomic asymmetry and cardiovascular control: Looking at the right side of stroke. Clin Auton Res. 34:549–560. 2024. View Article : Google Scholar : PubMed/NCBI

251 

Hyam JA, Kringelbach ML, Silburn PA, Aziz TZ and Green AL: The autonomic effects of deep brain stimulation-a therapeutic opportunity. Nat Rev Neurol. 8:391–400. 2012. View Article : Google Scholar : PubMed/NCBI

252 

Marins FR, Limborço-Filho M, Xavier CH, Biancardi VC, Vaz GC, Stern JE, Oppenheimer SM and Fontes MA: Functional topography of cardiovascular regulation along the rostrocaudal axis of the rat posterior insular cortex. Clin Exp Pharmacol Physiol. 43:484–493. 2016. View Article : Google Scholar : PubMed/NCBI

253 

Shivkumar K, Ajijola OA, Anand I, Armour JA, Chen PS, Esler M, De Ferrari GM, Fishbein MC, Goldberger JJ, Harper RM, et al: Clinical neurocardiology defining the value of neuroscience-based cardiovascular therapeutics. J Physiol. 594:3911–3954. 2016. View Article : Google Scholar : PubMed/NCBI

254 

Sumi K, Katayama Y, Otaka T, Obuchi T, Kano T, Kobayashi K, Oshima H, Fukaya C, Yamamoto T, Ogawa Y and Iwasaki K: Effect of subthalamic nucleus deep brain stimulation on the autonomic nervous system in Parkinson's disease patients assessed by spectral analyses of R-R interval variability and blood pressure variability. Stereotact Funct Neurosurg. 90:248–254. 2012. View Article : Google Scholar : PubMed/NCBI

255 

Zhang C, Xu J, Wu B, Ling Y, Guo Q, Wang S, Liu L, Jiang N, Chen L and Liu J: Subthalamic nucleus deep brain stimulation treats Parkinson's disease patients with cardiovascular disease comorbidity: A retrospective study of a single center experience. Brain Sci. 13:702022. View Article : Google Scholar

256 

Rajkumar S, Venkatraman V, Yang LZ, Parente B, Lee HJ and Lad SP: Short-term health care costs of high-frequency spinal cord stimulation for the treatment of postsurgical persistent spinal pain syndrome. Neuromodulation. 26:1450–1458. 2023. View Article : Google Scholar : PubMed/NCBI

257 

Kumar K, Caraway DL, Rizvi S and Bishop S: Current challenges in spinal cord stimulation. Neuromodulation. 17(Suppl 1): S22–S35. 2014. View Article : Google Scholar

258 

Yap JYY, Keatch C, Lambert E, Woods W, Stoddart PR and Kameneva T: Critical review of transcutaneous vagus nerve stimulation: Challenges for translation to clinical practice. Front Neurosci. 14:2842020. View Article : Google Scholar : PubMed/NCBI

259 

Austelle CW, Cox SS, Wills KE and Badran BW: Vagus nerve stimulation (VNS): Recent advances and future directions. Clin Auton Res. 34:529–547. 2024. View Article : Google Scholar : PubMed/NCBI

260 

Javan-Noughabi J, Rezapour A, Hajahmadi M and Alipour V: Economic evaluation of single-photon emission-computed tomography versus stress echocardiography in stable chest pain patients. Sci Rep. 12:152232022. View Article : Google Scholar : PubMed/NCBI

261 

Hijazi W, Vandenberk B, Rennert-May E, Quinn A, Sumner G and Chew DS: Economic evaluation in cardiac electrophysiology: Determining the value of emerging technologies. Front Cardiovasc Med. 10:11424292023. View Article : Google Scholar : PubMed/NCBI

262 

Tabaja H, Yuen J, Tai DBG, Campioli CC, Chesdachai S, DeSimone DC, Hassan A, Klassen BT, Miller KJ, Lee KH and Mahmood M: Deep brain stimulator device infection: The mayo clinic rochester experience. Open Forum Infect Dis. 10:ofac6312022. View Article : Google Scholar

263 

Jung IH, Chang KW, Park SH, Chang WS, Jung HH and Chang JW: Complications After deep brain stimulation: A 21-year experience in 426 patients. Front Aging Neurosci. 14:8197302022. View Article : Google Scholar : PubMed/NCBI

264 

Olson MC, Shill H, Ponce F and Aslam S: Deep brain stimulation in PD: Risk of complications, morbidity, and hospitalizations: A systematic review. Front Aging Neurosci. 15:12581902023. View Article : Google Scholar : PubMed/NCBI

265 

Lee JM, Lee D, Christiansen S, Hagedorn JM, Chen Z and Deer T: Spinal cord stimulation in special populations: Best practices from the american society of pain and neuroscience to improve safety and efficacy. J Pain Res. 15:3263–3273. 2022. View Article : Google Scholar : PubMed/NCBI

266 

Ki YM, Park HJ, Yi SH, Sim WS and Lee JY: Latent infection after spinal cord stimulation device implantation for complex regional pain syndrome: A case report. Medicine (Baltimore). 102:e337502023. View Article : Google Scholar : PubMed/NCBI

267 

Vu PD, Pinkhasova D, Sarwary ZB, Rita Markaryan A, Mousa B, Viswanath O, Robinson CL, Varrassi G, Orhurhu V, Urits I and Hasoon J: Biologic complications associated with cylindrical lead spinal cord stimulator implants: A narrative review. Orthop Rev (Pavia). 16:1234432024. View Article : Google Scholar : PubMed/NCBI

268 

Das S, Matias CM, Ramesh S, Velagapudi L, Barbera JP, Katz S, Baldassari MP, Rasool M, Kremens D, Ratliff J, et al: Capturing initial understanding and impressions of surgical therapy for Parkinson's disease. Front Neurol. 12:6059592021. View Article : Google Scholar : PubMed/NCBI

269 

Salinas M, Yazdani U, Oblack A, McDaniels B, Ahmed N, Haque B, Pouratian N and Chitnis S: Know DBS: Patient perceptions and knowledge of deep brain stimulation in Parkinson's disease. Ther Adv Neurol Disord. 17:175628642412330382024. View Article : Google Scholar : PubMed/NCBI

270 

Müller O and Rotter S: Neurotechnology: Current developments and ethical issues. Front Syst Neurosci. 11:932017. View Article : Google Scholar

271 

Faltus T, Freise J, Fluck C and Zillmann H: Ethics and regulation of neuronal optogenetics in the European Union. Pflugers Arch. 475:1505–1517. 2023. View Article : Google Scholar : PubMed/NCBI

272 

Jog MA, Anderson C, Kubicki A, Boucher M, Leaver A, Hellemann G, Iacoboni M, Woods R and Narr K: Transcranial direct current stimulation (tDCS) in depression induces structural plasticity. Sci Rep. 13:28412023. View Article : Google Scholar : PubMed/NCBI

273 

Lapa JDS, Duarte JFS, Campos ACP, Davidson B, Nestor SM, Rabin JS, Giacobbe P, Lipsman N and Hamani C: Adverse effects of deep brain stimulation for treatment-resistant depression: A scoping review. Neurosurgery. 95:509–516. 2024. View Article : Google Scholar : PubMed/NCBI

274 

Siebner HR, Funke K, Aberra AS, Antal A, Bestmann S, Chen R, Classen J, Davare M, Di Lazzaro V, Fox PT, et al: Transcranial magnetic stimulation of the brain: What is stimulated?-A consensus and critical position paper. Clin Neurophysiol. 140:59–97. 2022. View Article : Google Scholar : PubMed/NCBI

275 

Iseger TA, van Bueren NER, Kenemans JL, Gevirtz R and Arns M: A frontal-vagal network theory for major depressive disorder: Implications for optimizing neuromodulation techniques. Brain Stimul. 13:1–9. 2020. View Article : Google Scholar

276 

Jiao Y, Cheng C, Jia M, Chu Z, Song X, Zhang M, Xu H, Zeng X, Sun JB, Qin W and Yang XJ: Neuro-cardiac-guided transcranial magnetic stimulation: Unveiling the modulatory effects of low-frequency and high-frequency stimulation on heart rate. Psychophysiology. 61:e146312024. View Article : Google Scholar : PubMed/NCBI

277 

Zou N, Zhou Q, Zhang Y, Xin C, Wang Y, Claire-Marie R, Rong P, Gao G and Li S: Transcutaneous auricular vagus nerve stimulation as a novel therapy connecting the central and peripheral systems: A review. Int J Surg. 110:4993–5006. 2024. View Article : Google Scholar : PubMed/NCBI

278 

Afra P, Adamolekun B, Aydemir S and Watson GDR: Evolution of the vagus nerve stimulation (VNS) therapy system technology for drug-resistant epilepsy. Front Med Technol. 3:6965432021. View Article : Google Scholar

279 

Habibagahi I, Omidbeigi M, Hadaya J, Lyu H, Jang J, Ardell JL, Bari AA and Babakhani A: Vagus nerve stimulation using a miniaturized wirelessly powered stimulator in pigs. Sci Rep. 12:81842022. View Article : Google Scholar : PubMed/NCBI

280 

Mirza KB, Golden CT, Nikolic K and Toumazou C: Closed-loop implantable therapeutic neuromodulation systems based on neurochemical monitoring. Front Neurosci. 13:8082019. View Article : Google Scholar : PubMed/NCBI

281 

de Faria GM, Lopes EG, Tobaldini E, Montano N, Cunha TS, Casali KR and de Amorim HA: Advances in non-invasive neuromodulation: Designing closed-loop devices for respiratory-controlled transcutaneous vagus nerve stimulation. Healthcare (Basel). 12:312023. View Article : Google Scholar

282 

Van Horn JD, Grafton ST and Miller MB: Individual variability in brain activity: A nuisance or an opportunity? Brain Imaging Behav. 2:327–334. 2008. View Article : Google Scholar

283 

Li LM, Uehara K and Hanakawa T: The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies. Front Cell Neurosci. 9:1812015. View Article : Google Scholar : PubMed/NCBI

284 

Seghier ML and Price CJ: Interpreting and utilising intersubject variability in brain function. Trends Cogn Sci. 22:517–530. 2018. View Article : Google Scholar : PubMed/NCBI

285 

Johnson MD, Lim HH, Netoff TI, Connolly AT, Johnson N, Roy A, Holt A, Lim KO, Carey JR, Vitek JL and He B: Neuromodulation for brain disorders: Challenges and opportunities. IEEE Trans Biomed Eng. 60:610–624. 2013. View Article : Google Scholar : PubMed/NCBI

286 

Völzke H, Schmidt CO, Baumeister SE, Ittermann T, Fung G, Krafczyk-Korth J, Hoffmann W, Schwab M, Meyer zu Schwabedissen HE, Dörr M, et al: Personalized cardiovascular medicine: Concepts and methodological considerations. Nat Rev Cardiol. 10:308–316. 2013. View Article : Google Scholar : PubMed/NCBI

287 

Thompson N, Mastitskaya S and Holder D: Avoiding off-target effects in electrical stimulation of the cervical vagus nerve: Neuroanatomical tracing techniques to study fascicular anatomy of the vagus nerve. J Neurosci Methods. 325:1083252019. View Article : Google Scholar : PubMed/NCBI

288 

Fitchett A, Mastitskaya S and Aristovich K: Selective neuromodulation of the vagus nerve. Front Neurosci. 15:6858722021. View Article : Google Scholar : PubMed/NCBI

289 

Sclocco R, Garcia RG, Gabriel A, Kettner NW, Napadow V and Barbieri R: Respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) effects on autonomic outflow in hypertension. Annu Int Conf IEEE Eng Med Biol Soc. 2017:3130–3133. 2017.PubMed/NCBI

290 

Garcia RG, Cohen JE, Stanford AD, Gabriel A, Stowell J, Aizley H, Barbieri R, Gitlin D, Napadow V and Goldstein JM: Respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) modulates brain response to stress in major depression. J Psychiatr Res. 142:188–197. 2021. View Article : Google Scholar : PubMed/NCBI

291 

Cook DN, Thompson S, Stomberg-Firestein S, Bikson M, George MS, Jenkins DD and Badran BW: Design and validation of a closed-loop, motor-activated auricular vagus nerve stimulation (MAAVNS) system for neurorehabilitation. Brain Stimul. 13:800–803. 2020. View Article : Google Scholar : PubMed/NCBI

292 

Badran BW, Peng X, Baker-Vogel B, Hutchison S, Finetto P, Rishe K, Fortune A, Kitchens E, O'Leary GH, Short A, et al: Motor activated auricular vagus nerve stimulation as a potential neuromodulation approach for post-stroke motor rehabilitation: A pilot study. Neurorehabil Neural Repair. 37:374–383. 2023. View Article : Google Scholar : PubMed/NCBI

293 

Yu Y, Ling J, Yu L, Liu P and Jiang M: Closed-loop transcutaneous auricular vagal nerve stimulation: Current situation and future possibilities. Front Hum Neurosci. 15:7856202022. View Article : Google Scholar : PubMed/NCBI

294 

Forrest IS, Petrazzini BO, Duffy Á, Park JK, Marquez-Luna C, Jordan DM, Rocheleau G, Cho JH, Rosenson RS, Narula J, et al: Machine learning-based marker for coronary artery disease: Derivation and validation in two longitudinal cohorts. Lancet. 401:215–225. 2023. View Article : Google Scholar :

295 

Upton R, Mumith A, Beqiri A, Parker A, Hawkes W, Gao S, Porumb M, Sarwar R, Marques P, Markham D, et al: Automated echocardiographic detection of severe coronary artery disease using artificial intelligence. JACC Cardiovasc Imaging. 15:715–727. 2022. View Article : Google Scholar

296 

Alizadehsani R, Abdar M, Roshanzamir M, Khosravi A, Kebria PM, Khozeimeh F, Nahavandi S, Sarrafzadegan N and Acharya UR: Machine learning-based coronary artery disease diagnosis: A comprehensive review. Comput Biol Med. 111:1033462019. View Article : Google Scholar : PubMed/NCBI

297 

Obst MA, Al-Zubaidi A, Heldmann M, Nolde JM, Blümel N, Kannenberg S and Münte TF: Five weeks of intermittent transcutaneous vagus nerve stimulation shape neural networks: A machine learning approach. Brain Imaging Behav. 16:1217–1233. 2022. View Article : Google Scholar :

298 

Tarasenko A, Guazzotti S, Minot T, Oganesyan M and Vysokov N: Determination of the effects of transcutaneous auricular vagus nerve stimulation on the heart rate variability using a machine learning pipeline. Bioelectricity. 4:168–177. 2022. View Article : Google Scholar : PubMed/NCBI

299 

Chen H, Lai H, Chi H, Fan W, Huang J, Zhang S, Jiang C, Jiang L, Hu Q, Yan X, et al: Multi-modal transcriptomics: integrating machine learning and convolutional neural networks to identify immune biomarkers in atherosclerosis. Front Cardiovasc Med. 11:13974072024. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu Y, Yang H, Xiong J, Wei Y, Yang C, Zheng Q and Liang F: Brain‑heart axis: Neurostimulation techniques in ischemic heart disease (Review). Int J Mol Med 56: 148, 2025.
APA
Liu, Y., Yang, H., Xiong, J., Wei, Y., Yang, C., Zheng, Q., & Liang, F. (2025). Brain‑heart axis: Neurostimulation techniques in ischemic heart disease (Review). International Journal of Molecular Medicine, 56, 148. https://doi.org/10.3892/ijmm.2025.5589
MLA
Liu, Y., Yang, H., Xiong, J., Wei, Y., Yang, C., Zheng, Q., Liang, F."Brain‑heart axis: Neurostimulation techniques in ischemic heart disease (Review)". International Journal of Molecular Medicine 56.4 (2025): 148.
Chicago
Liu, Y., Yang, H., Xiong, J., Wei, Y., Yang, C., Zheng, Q., Liang, F."Brain‑heart axis: Neurostimulation techniques in ischemic heart disease (Review)". International Journal of Molecular Medicine 56, no. 4 (2025): 148. https://doi.org/10.3892/ijmm.2025.5589
Copy and paste a formatted citation
x
Spandidos Publications style
Liu Y, Yang H, Xiong J, Wei Y, Yang C, Zheng Q and Liang F: Brain‑heart axis: Neurostimulation techniques in ischemic heart disease (Review). Int J Mol Med 56: 148, 2025.
APA
Liu, Y., Yang, H., Xiong, J., Wei, Y., Yang, C., Zheng, Q., & Liang, F. (2025). Brain‑heart axis: Neurostimulation techniques in ischemic heart disease (Review). International Journal of Molecular Medicine, 56, 148. https://doi.org/10.3892/ijmm.2025.5589
MLA
Liu, Y., Yang, H., Xiong, J., Wei, Y., Yang, C., Zheng, Q., Liang, F."Brain‑heart axis: Neurostimulation techniques in ischemic heart disease (Review)". International Journal of Molecular Medicine 56.4 (2025): 148.
Chicago
Liu, Y., Yang, H., Xiong, J., Wei, Y., Yang, C., Zheng, Q., Liang, F."Brain‑heart axis: Neurostimulation techniques in ischemic heart disease (Review)". International Journal of Molecular Medicine 56, no. 4 (2025): 148. https://doi.org/10.3892/ijmm.2025.5589
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