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Liraglutide suppresses atrial electrophysiological changes

  • Hironori Nakamura
  • Shinichi NiwanoEmail author
  • Hiroe Niwano
  • Hidehira Fukaya
  • Masami Murakami
  • Jun Kishihara
  • Akira Satoh
  • Tomoharu Yoshizawa
  • Naruya Ishizue
  • Tazuru Igarashi
  • Tamami Fujiishi
  • Junya Ako
Short Communication

Abstract

We have shown that a dipeptidyl peptidase 4 (DPP-4) inhibitor suppresses atrial remodeling in a canine atrial fibrillation (AF) model. Glucagon-like peptide-1 (GLP-1) is increased by DPP-4 inhibitors. However, it is not clear whether GLP-1 is involved in the suppression of atrial remodeling. In this study, we evaluated the effect of liraglutide (a GLP-1 analog) on atrial electrophysiological changes using the same canine AF model. We established a canine AF model using continuous 3-week rapid atrial stimulation in seven beagle dogs divided into two groups: a liraglutide group with four dogs (3-week atrial pacing with liraglutide (150 µg/kg/day) administration) and a pacing control group with three dogs (3-week pacing without any medicine). We evaluated the atrial effective refractory period (AERP), conduction velocity (CV), and AF inducibility every week during the protocol using implanted epicardial wires against the surfaces of both atria. In the pacing control group, the AERP was gradually shortened and the CV was decreased along the time course. In the liraglutide group, the AERP was similarly shortened as in the pacing control group (94 ± 4% versus 85 ± 2%, respectively; p = 0.5926), but the CV became significantly higher than that in the pacing control group after 2 and 3 weeks (95 ± 4 versus 83 ± 5%, respectively; p = 0.0339). The AF inducibility was gradually increased in the pacing control group, but it was suppressed in the liraglutide group (5 ± 9% versus 73 ± 5%; p = 0.0262). Liraglutide suppressed electrophysiological changes such as AF inducibility and CV decrease in our canine AF model.

Keywords

GLP-1 Atrial fibrillation Remodeling 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Dzeshka MS, Lip GY, Snezhitskiy V, Shantsila E (2015) Cardiac fibrosis in patients with atrial fibrillation: mechanisms and clinical implications. J Am Coll Cardiol 66(8):943–959CrossRefGoogle Scholar
  2. 2.
    Igarashi T, Niwano S, Niwano H, Yoshizawa T, Nakamura H, Fukaya H, Fujiishi T, Ishizue N, Satoh A, Kishihara J, Murakami M, Ako J (2018) Linagliptin prevents atrial electrical and structural remodeling in a canine model of atrial fibrillation. Heart Vessels 33(10):1258–1265CrossRefGoogle Scholar
  3. 3.
    Lebovitz HE, Banerji MA (2012) Non-insulin injectable treatments (glucagon-like peptide-1 and its analogs) and cardiovascular disease. Diabetes Technol Ther 14:S43–S50CrossRefGoogle Scholar
  4. 4.
    Liu Q, Anderson C, Broyde A, Polizzi C, Fernandez R, Baron A, Parkes DG (2010) Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure. Cardiovasc Diabetol 9:76CrossRefGoogle Scholar
  5. 5.
    Sonne DP, Engstrøm T, Treiman M (2008) Protective effects of GLP-1 analogues exendin-4 and GLP-1(9–36) amide against ischemia-reperfusion injury in rat heart. Regul Pept 146:243–249CrossRefGoogle Scholar
  6. 6.
    Satoh A, Niwano S, Niwano H, Kishihara J, Aoyama Y, Oikawa J, Fukaya H, Tamaki H, Ako J (2017) Aliskiren suppresses atrial electrical and structural remodeling in a canine model of atrial fibrillation. Heart Vessels 32(1):90–100CrossRefGoogle Scholar
  7. 7.
    Kishihara J, Niwano S, Niwano H, Aoyama Y, Satoh A, Oikawa J, Kiryu M, Fukaya H, Masaki Y, Tamaki H, Izumi T, Ako J (2014) Effect of carvedilol on atrial remodeling in canine model of atrial fibrillation. Cardiovasc Diagn Ther 4(1):28–35Google Scholar
  8. 8.
    Nattel S, Maguy A, Le Bouter S, Yeh YH (2007) Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial infarction, and atrial fibrillation. Physiol Rev 87(2):425–456CrossRefGoogle Scholar
  9. 9.
    Bosch RF, Scherer CR, Rüb N, Wöhrl S, Steinmeyer K, Haase H, Busch AE, Seipel L, Kühlkamp V (2003) Molecular mechanisms of early electrical remodeling: transcriptional downregulation of ion channel subunits reduces I(Ca, L) and I(to) in rapid atrial pacing in rabbits. J Am Coll Cardiol 41(5):858–869CrossRefGoogle Scholar
  10. 10.
    Gaspo R, Bosch RF, Bou-Abboud E, Nattel S (1997) Tachycardia-induced changes in Na+ current in a chronic dog model of atrial fibrillation. Circ Res 81(6):1045–1052CrossRefGoogle Scholar
  11. 11.
    Yue L, Melnyk P, Gaspo R, Wang Z, Nattel S (1999) Molecular mechanisms underlying ionic remodeling in a dog model of atrial fibrillation. Circ Res 84(7):776–784CrossRefGoogle Scholar
  12. 12.
    Olson TM, Michels VV, Ballew JD, Reyna SP, Karst ML, Herron KJ, Horton SC, Rodeheffer RJ, Anderson JL (2005) Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA 293(4):447–454CrossRefGoogle Scholar
  13. 13.
    Nattel S, Harada M (2014) Atrial remodeling and atrial fibrillation: recent advances and translational perspectives. J Am Coll Cardiol 63(22):2335–2345CrossRefGoogle Scholar
  14. 14.
    Huang JH, Chen YC, Lee TI, Kao YH, Chazo TF, Chen SA, Chen Y (2016) Glucagon-like peptide-1 regulates calcium homeostasis and electrophysiological activities of HL-1 cardiomyocytes. Peptides 78:91–98CrossRefGoogle Scholar
  15. 15.
    Fujita H, Morii T, Fujishima H, Sato T, Shimizu T, Hosoba M, Tsukiyama K, Narita T, Takahashi T, Drucker DJ, Seino Y, Yamada Y (2014) The protective roles of GLP-1R signaling in diabetic nephropathy: possible mechanism and therapeutic potential. Kidney Int 85(3):579–589CrossRefGoogle Scholar
  16. 16.
    Timmers L, Henriques JP, de Kleijn DP, Devries JH, Kemperman H, Steendijk P, Verlaan CW, Kerver M, Piek JJ, Doevendans PA, Pasterkamp G, Hoefer IE (2009) Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury. J Am Coll Cardiol 53(6):501–510CrossRefGoogle Scholar
  17. 17.
    Tashiro Y, Sato K, Watanabe T, Nohtomi K, Terasaki M, Nagashima M, Hirano T (2014) A glucagon-like peptide-1 analog liraglutide suppresses macrophage foam cell formation and atherosclerosis. Peptides 54:19–26CrossRefGoogle Scholar
  18. 18.
    Warbrick I, Rabkin SW (2018) Effect of the peptides relaxin, neuregulin, ghrelin and glucagon-like peptide-1, on cardiomyocyte factors involved in the molecular mechanisms leading to diastolic dysfunction and/or heart failure with preserved ejection fraction. Peptides.  https://doi.org/10.1016/j.peptides.2018.05.009 Google Scholar

Copyright information

© The Founding-Editors Group 2019

Authors and Affiliations

  • Hironori Nakamura
    • 1
  • Shinichi Niwano
    • 1
    Email author
  • Hiroe Niwano
    • 1
  • Hidehira Fukaya
    • 1
  • Masami Murakami
    • 1
  • Jun Kishihara
    • 1
  • Akira Satoh
    • 1
  • Tomoharu Yoshizawa
    • 1
  • Naruya Ishizue
    • 1
  • Tazuru Igarashi
    • 1
  • Tamami Fujiishi
    • 1
  • Junya Ako
    • 1
  1. 1.Department of Cardiovascular MedicineKitasato University School of MedicineSagamiharaJapan

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