Next-generation pacemakers: from electrical devices to biological pacemakers

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Abstract

The invention of an electric pacemaker in the middle of the 20th century led to a revolution in the treatment of cardiac conduction system diseases. The improvement of pacemakers continued. In 1962, the first small series of external pacemakers for percutaneous and direct stimulation was produced in Kaunas. After a while, electric pacemakers became more reliable, smaller and lighter in weight, but the problem of foreign body associated infection and limited service life remained unresolved. Modern high-tech medicine strives to create less invasive electric pacemakers, but nevertheless, biological pacemakers can expand the therapeutic arsenal for the treatment of cardiac patients, being the most physiological for humans. The concept of an artificial biological pacemaker consists of the creation of an organic structure that generates a spontaneous rhythm from the implantation site in the myocardium. Various gene and cellular approaches were used to create biological pacemakers: a functional reorganization approach (use of adenovirus vectors for hyperexpression of genes encoding ion channels in cardiomyocytes); hybrid approach (use of fibroblasts to deliver genes of ion channels that provide heart automation); somatic reprogramming approach (overexpression of the transcription factor TBX18 using adenoviral vectors, which reprograms cardiomyocytes into induced sinoatrial node cells, creating cardiac stimulatory activity); cellular approach (transplantation of stem cells to a specific place in the heart, thereby creating biological stimulation). Modern methods of electrical cardiac stimulation and the developed concepts of the biological pacemaker clearly show the possibility of eliminating current problems associated with the use of an artificial pacemaker by replacing it with a biological one. Each of the approaches (gene, cellular, hybrid-cellular, somatic reprogramming) has its own advantages and disadvantages, which predisposes to further study and improvement in order to introduce a biological pacemaker into clinical practice.

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About the authors

V N Oslopov

Kazan (Volga region) Federal University

Email: osnebaa@mail.ru
Russian Federation, Kazan, Russia

A Kh Mamedova

Kazan State Medical University

Author for correspondence.
Email: osnebaa@mail.ru
Russian Federation, Kazan, Russia

D N Nafeeva

Kazan State Medical University

Email: osnebaa@mail.ru
Russian Federation, Kazan, Russia

E V Khazova

Kazan State Medical University

Email: osnebaa@mail.ru
Russian Federation, Kazan, Russia

Yu V Oslopova

Kazan (Volga region) Federal University

Email: osnebaa@mail.ru
Russian Federation, Kazan, Russia

References

  1. Anderson R.H., Boyett M.R., Dobrzynski H., Moorman A.F. The anatomy of the conduction system: implications for the clinical cardiologist. J. Cardiovasc. Transl. Res. 2013; 6: 187–196. doi: 10.1007/s12265-012-9433-0.
  2. Anderson R.H., Ho S.Y. The architecture of the sinus node, the atrioventricular conduction axis, and the х atrial myocardium. J. Cardiovasc. Electrophysiol. 1998; 9: 1233–1248. doi: 10.1111/j.1540-8167.1998.tb00097.x.
  3. Fortescue E.B., Berul C.I., Cecchin F., Walsh E.P., Triedman J.K., Alexander M.E. Patient, procedural, and hardware factors associated with pacemaker lead failures in pediatrics and congenital heart disease. Hear. Rhythm. 2004; 1: 150–159. doi: 10.1016/j.hrthm.2004.02.020.
  4. Dagdeviren C., Yan S., Joe P., Ghaffari R., Balooch G., Usgaonkar K., Onur Gur, Phat L.T., Jessi R.C., Meyer M., Yewang S.R., Webb C., Tedesco A.S. Conformal piezoelectric systems for clinical and experimental characterization of soft tissue biomechanics. Nat. Mater. 2015; 14: 728–736. doi: 10.1038/nmat4289.
  5. Dagdeviren C., Yan S., Joe P., Ghaffari R., Balooch G., Usgaonkar K., Onur Gur, Phat L.T., Jessi R.C., Meyer M., Yewang S.R., Webb C., Tedesco A.S. Conformal piezoelectric energy harvesting and storage from motions of the heart, lung, and diaphragm. Proc. Natl. Acad. Sci. USA. 2014; 111: 1927–1932. doi: 10.1073/pnas.1317233111.
  6. Haeberlin A., Zurbuchen A., Walpen S., Schaerer J., Niederhauser T., Huber C., Tanner H., Servatius H., Seiler J., Haeberlin H., Fuhrer J., Vogel R. The first batteryless, solar-powered cardiac pacemaker. Heart Rhythm. 2015; 12: 1317–1323. doi: 10.1016/j.hrthm.2015.02.032.
  7. Van Weerd J.H., Christoffels V.M. The formation and function of the cardiac conduction system. Development. 2016; 143: 197–210. doi: 10.1242/dev.124883.
  8. Cohen I., Brink P., Robinson B., Rosen M. The why, what, how and when of biological pacemaker. Nature Clin. Pract. 2005; 2: 374–375. doi: 10.1038/ncpcardio0276.
  9. Cingolani E., Marbán E. Recreating the sinus node by somatic reprogramming: a dream come true? Rev. Esp. Cardiol. 2015; 68: 743–745. doi: 10.1016/j.rec.2015.04.011.
  10. Hu Y.F., Dawkins J.F., Cho H.C., Marban E., Cingolani E. Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block. Sci. Transl. Med. 2014; 6: 245ra94. doi: 10.1126/scitranslmed.3008681.
  11. Chauveau S., Anyukhovsky E.P., Ben-Ari M., Naor S., Jiang Y.P., Danilo P.Jr., Rahim T., Burke S., Qiu X., Potapova I.A. Induced pluripotent stem cell-derived cardiomyocytes provide in vivo biological pacemaker function. Circ. Arrhythm. Electrophysiol. 2017; 10: e004508. doi: 10.1161/CIRCEP.116.004508.
  12. Liechty K.W., Mackenzie T.C., Shaaban A.F., Radu A., Moseley A.B., Deans R., Marshak D.R., Flake A.W. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat. Med. 2000; 6: 1282–1286. doi: 10.1038/81395.
  13. Lloyd M., Reynolds D., Sheldon T., Stromberg K., Hudna H.T., Demmer W.M., Omar R., Ritter P., Hummel J., Mont L., Steinwender C., Duray G.Z. Rate adaptive pacing in an intracardiac pacemaker. Heart Rhythm. 2017; 14: 200–205. doi: 10.1016/j.hrthm.2016.11.016.
  14. Edelberg J.M., Aird W.C., Rosenberg R.D. Enhancement of murine cardiac chronotropy by the molecular transfer of the human β2 adrenergic receptor cDNA. J. Clin. Invest. 1998; 101: 337–343. doi: 10.1172/JCI1330.
  15. Edelberg J.M., Huang D.T., Josephson M.E., Rosenberg R.D. Molecular enhancement of porcine cardiac chronotropy. Heart. 2001; 86: 559–562. doi: 10.1136/heart.86.5.559.
  16. Riedel M., Jou C.J., Lai S., Lux R.L., Moreno A.P., Spitzer K.W., Christians E., Tristani-Firouzi M., Benjamin I.J. Functional and pharmacological analysis of cardiomyocytes differentiated from human peripheral blood mononuclear-derived pluripotent stem cells. Stem. Cell Rep. 2014; 3: 131–141. doi: 10.1016/j.stemcr.2014.04.017.
  17. Baruscotti M., Bucchi A., Difrancesco D. Physiology and pharmacology of the cardiac pacemaker (“funny”) current. Pharmacol. Ther. 2005; 107: 59–79. doi: 10.1016/j.pharmthera.2005.01.005.
  18. Zhang H., David H.L., Shlapakova I.N., Zhao X., Danilo P., Robinson R.B., Cohen I.S., Dan Qu, Zhiyun Xu, Rosen M.R. Implantation of sinoatrial node cells into canine right ventricle: Biological pacing appears limited by the substrate. Cell Transplant. 2011; 20 (11–12): 1907–1914. doi: 10.3727/096368911X565038b.
  19. Silva J., Rudy Y. Mechanism of pacemaking in Ik1-downregulated myocytes. Circul. Res. 2003; 92: 261–263. doi: 10.1161/01.RES.0000057996.20414.C6.
  20. Xu C., Police S., Rao N., Carpenter M.K. Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circul. Res. 2002; 91: 501–508. doi: 10.1161/01.RES.0000035254.80718.91.
  21. Xue T., Cho H.C., Akar F.G., Tsang S., Jones S.P., Marban E., Tomaselli G.F., Li R.A. Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: insights into the development of cell-based pacemakers. Circulation. 2005; 111: 11–20. doi: 10.1161/01.CIR.0000151313.18547.A2.
  22. Protze S.I., Liu J., Nussinovitch U., Ohana L., Backx P.H., Gepstein L., Keller G.M. Sinoatrial node cardiomyocytes derived from human pluripotent cells function as a biological pacemaker. Nat. Biotechnol. 2017; 35: 56–68. doi: 10.1038/nbt.3745.
  23. Kaupp U.B., Seifert R. Molecular diversity of pacemaker ion channels. Annu. Rev. Physiol. 2001; 63: 235–257. doi: 10.1146/annurev.physiol.63.1.235.
  24. Zagidullin N.Sh., Zagidullin Sh.Z. The opportunities of biological pacemakers construction by sinus node impairement. Meditsinskiy vestnik Bashkortostana. 2008; 3 (1): 51–56. (In Russ)
  25. Zagidullin N.S., Zagidullin S.Z. Electrophysiological characterization of cardio specific isoforms of the If channel. Kazan Medical Journal. 2009; 90 (2): 27–31. (In Russ.)
  26. Plotnikov A.N., Shlapakova I., Szabolcs M.J., Jr P.D., Lorell B.N., Potapova I.A., Lu Z., Rosen A.B., Mathias R.T., Brink P.R., Robinson R.B., Cohen I.S., Rosen M.R. Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart. Circulation. 2007; 116: 706–713. doi: 10.1161/CIRCULATIONAHA.107.703231.
  27. Cho H.C., Kashiwakura Y., Marban E. Creation of a biological pacemaker by cell fusion. Circuí. Res. 2007; 100: 1112–1115. doi: 10.1161/01.RES.0000265845.04439.78.
  28. Bucchi A., Plotnikov A.N., Shlapakova I., Jr P.D., Kryukova Y., Qu J., Lu Z., Liu H., Pan Z., Potapova I., KenKnight B., Girouard S., Cohen I.S., Brink P.S., Robinson R.B., Rosen M.R. Wild-type and mutant HCN channels in a tandem biological-electronic cardiac pacemaker. Circulation. 2006; 114: 992–999. doi: 10.1161/CIRCULATIONAHA.106.617613.
  29. Kapoor N., Liang W., Marbán E., Cho H.C. Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18. Nature Biotechnol. 2012; 31 (1): 54–62. doi: 10.1038/nbt.2465.
  30. Lown B., Axelrod P. Implanted standby defibrillators. Circuíation. 1972; 46: 637–639. doi: 10.1161/01.CIR.46.4.637.
  31. Mirowski M., Philip R., Mower M.M., Watkins L., Gott V.L., Schauble J.F., Langer A., Heilman M.S., Kolenik S.A., Fischell R.E., Weisfeldt M.L. Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N. Eng. J. Med. 1980: 303: 322–324. doi: 10.1056/NEJM198008073030607.
  32. Mond H.G., Proclemer A. The 11th world survey of cardiac pacing and implantable cardioverter-defibrillators: calendar year 2009 — a World Society of Arrhythmia’s project. Pacing Cíin. Eíectrophysio. 2011: 34: 1013–1027. doi: 10.1111/j.1540-8159.2011.03150.x.
  33. Bolli R. Dandum semper est tempus: the crucial importance of (and increasing disregard for) the test of time. Circuí. Res. 2015: 117: 755–757. doi: 10.1161/CIRCRESAHA.115.307613.
  34. Oslopov V.N., Milyutina O.I., Milyutina I.I. Biological pacemaker: possibility and technique of development. Prakticheskaya meditsina. 2020; 18 (1): 32–37. (In Russ.)

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