Open thoracic surgical implantation of cardiac pacemakers in rats

Rose T. Yin; Sheena W. Chen; K. Benjamin Lee; Yeon Sik Choi; Jahyun Koo; Quansan Yang; Michael A. Napolitano; Jokubas Ausra; Timothy J. Holleran; Jessica B. Lapiano; E. Alex Waters; Anlil Brikha; Grant Kowalik; Alana N. Miniovich; Helen S. Knight; Bender A. Russo; Alexi Kiss; Alejandro Murillo-Berlioz; Tatiana Efimova; Chad R. Haney; Philipp Gutruf; John A. Rogers; Gregory D. Trachiotis; Igor R. Efimov

doi:10.1038/s41596-022-00770-y

Open thoracic surgical implantation of cardiac pacemakers in rats

Rose T. Yin, Sheena W. Chen, K. Benjamin Lee, Yeon Sik Choi, Jahyun Koo, Quansan Yang, Michael A. Napolitano, Jokubas Ausra, Timothy J. Holleran, Jessica B. Lapiano, E. Alex Waters, Anlil Brikha, Grant Kowalik, Alana N. Miniovich, Helen S. Knight, Bender A. Russo, Alexi Kiss, Alejandro Murillo-Berlioz, Tatiana Efimova, Chad R. HaneyPhilipp Gutruf, John A. Rogers, Gregory D. Trachiotis, Igor R. Efimov

Department of Materials Science and Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

Genetic engineering and implantable bioelectronics have transformed investigations of cardiovascular physiology and disease. However, the two approaches have been difficult to combine in the same species: genetic engineering is applied primarily in rodents, and implantable devices generally require larger animal models. We recently developed several miniature cardiac bioelectronic devices suitable for mice and rats to enable the advantages of molecular tools and implantable devices to be combined. Successful implementation of these device-enabled studies requires microsurgery approaches that reliably interface bioelectronics to the beating heart with minimal disruption to native physiology. Here we describe how to perform an open thoracic surgical technique for epicardial implantation of wireless cardiac pacemakers in adult rats that has lower mortality than transvenous implantation approaches. In addition, we provide the methodology for a full biocompatibility assessment of the physiological response to the implanted device. The surgical implantation procedure takes ~40 min for operators experienced in microsurgery to complete, and six to eight surgeries can be completed in 1 d. Implanted pacemakers provide programmed electrical stimulation for over 1 month. This protocol has broad applications to harness implantable bioelectronics to enable fully conscious in vivo studies of cardiovascular physiology in transgenic rodent disease models.

Original language	English
Pages (from-to)	374-395
Number of pages	22
Journal	Nature Protocols
Volume	18
Issue number	2
DOIs	https://doi.org/10.1038/s41596-022-00770-y
Publication status	Published - 2023 Feb

Bibliographical note

Funding Information:
We thank the staff of the Office of Animal Research at The George Washington University for their dedication in caring for our animals. We acknowledge funding by the Leducq Foundation (project RHYTHM) and NIH grant R01 HL141470 (I.R.E. and J.A.R.). R.T.Y. acknowledges support from the American Heart Association Predoctoral Fellowship (19PRE34380781). Y.S.C. acknowledges support from the NIH grant K99 HL155844. A.N.M. acknowledges support from the Henry Luce Foundation for the Luce Undergraduate Research Fellowship. E.A.W. acknowledges support from grant number 2020-225578 from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation.

Publisher Copyright:
© 2022, Springer Nature Limited.

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)

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10.1038/s41596-022-00770-y

Cite this

Yin, R. T., Chen, S. W., Benjamin Lee, K., Choi, Y. S., Koo, J., Yang, Q., Napolitano, M. A., Ausra, J., Holleran, T. J., Lapiano, J. B., Alex Waters, E., Brikha, A., Kowalik, G., Miniovich, A. N., Knight, H. S., Russo, B. A., Kiss, A., Murillo-Berlioz, A., Efimova, T., ... Efimov, I. R. (2023). Open thoracic surgical implantation of cardiac pacemakers in rats. Nature Protocols, 18(2), 374-395. https://doi.org/10.1038/s41596-022-00770-y

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title = "Open thoracic surgical implantation of cardiac pacemakers in rats",

abstract = "Genetic engineering and implantable bioelectronics have transformed investigations of cardiovascular physiology and disease. However, the two approaches have been difficult to combine in the same species: genetic engineering is applied primarily in rodents, and implantable devices generally require larger animal models. We recently developed several miniature cardiac bioelectronic devices suitable for mice and rats to enable the advantages of molecular tools and implantable devices to be combined. Successful implementation of these device-enabled studies requires microsurgery approaches that reliably interface bioelectronics to the beating heart with minimal disruption to native physiology. Here we describe how to perform an open thoracic surgical technique for epicardial implantation of wireless cardiac pacemakers in adult rats that has lower mortality than transvenous implantation approaches. In addition, we provide the methodology for a full biocompatibility assessment of the physiological response to the implanted device. The surgical implantation procedure takes ~40 min for operators experienced in microsurgery to complete, and six to eight surgeries can be completed in 1 d. Implanted pacemakers provide programmed electrical stimulation for over 1 month. This protocol has broad applications to harness implantable bioelectronics to enable fully conscious in vivo studies of cardiovascular physiology in transgenic rodent disease models.",

author = "Yin, {Rose T.} and Chen, {Sheena W.} and {Benjamin Lee}, K. and Choi, {Yeon Sik} and Jahyun Koo and Quansan Yang and Napolitano, {Michael A.} and Jokubas Ausra and Holleran, {Timothy J.} and Lapiano, {Jessica B.} and {Alex Waters}, E. and Anlil Brikha and Grant Kowalik and Miniovich, {Alana N.} and Knight, {Helen S.} and Russo, {Bender A.} and Alexi Kiss and Alejandro Murillo-Berlioz and Tatiana Efimova and Haney, {Chad R.} and Philipp Gutruf and Rogers, {John A.} and Trachiotis, {Gregory D.} and Efimov, {Igor R.}",

note = "Funding Information: We thank the staff of the Office of Animal Research at The George Washington University for their dedication in caring for our animals. We acknowledge funding by the Leducq Foundation (project RHYTHM) and NIH grant R01 HL141470 (I.R.E. and J.A.R.). R.T.Y. acknowledges support from the American Heart Association Predoctoral Fellowship (19PRE34380781). Y.S.C. acknowledges support from the NIH grant K99 HL155844. A.N.M. acknowledges support from the Henry Luce Foundation for the Luce Undergraduate Research Fellowship. E.A.W. acknowledges support from grant number 2020-225578 from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation. Publisher Copyright: {\textcopyright} 2022, Springer Nature Limited.",

year = "2023",

month = feb,

doi = "10.1038/s41596-022-00770-y",

language = "English",

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Yin, RT, Chen, SW, Benjamin Lee, K, Choi, YS, Koo, J, Yang, Q, Napolitano, MA, Ausra, J, Holleran, TJ, Lapiano, JB, Alex Waters, E, Brikha, A, Kowalik, G, Miniovich, AN, Knight, HS, Russo, BA, Kiss, A, Murillo-Berlioz, A, Efimova, T, Haney, CR, Gutruf, P, Rogers, JA, Trachiotis, GD & Efimov, IR 2023, 'Open thoracic surgical implantation of cardiac pacemakers in rats', Nature Protocols, vol. 18, no. 2, pp. 374-395. https://doi.org/10.1038/s41596-022-00770-y

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T1 - Open thoracic surgical implantation of cardiac pacemakers in rats

AU - Yin, Rose T.

AU - Chen, Sheena W.

AU - Benjamin Lee, K.

AU - Choi, Yeon Sik

AU - Koo, Jahyun

AU - Yang, Quansan

AU - Napolitano, Michael A.

AU - Ausra, Jokubas

AU - Holleran, Timothy J.

AU - Lapiano, Jessica B.

AU - Alex Waters, E.

AU - Brikha, Anlil

AU - Kowalik, Grant

AU - Miniovich, Alana N.

AU - Knight, Helen S.

AU - Russo, Bender A.

AU - Kiss, Alexi

AU - Murillo-Berlioz, Alejandro

AU - Efimova, Tatiana

AU - Haney, Chad R.

AU - Gutruf, Philipp

AU - Rogers, John A.

AU - Trachiotis, Gregory D.

AU - Efimov, Igor R.

N1 - Funding Information: We thank the staff of the Office of Animal Research at The George Washington University for their dedication in caring for our animals. We acknowledge funding by the Leducq Foundation (project RHYTHM) and NIH grant R01 HL141470 (I.R.E. and J.A.R.). R.T.Y. acknowledges support from the American Heart Association Predoctoral Fellowship (19PRE34380781). Y.S.C. acknowledges support from the NIH grant K99 HL155844. A.N.M. acknowledges support from the Henry Luce Foundation for the Luce Undergraduate Research Fellowship. E.A.W. acknowledges support from grant number 2020-225578 from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation. Publisher Copyright: © 2022, Springer Nature Limited.

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N2 - Genetic engineering and implantable bioelectronics have transformed investigations of cardiovascular physiology and disease. However, the two approaches have been difficult to combine in the same species: genetic engineering is applied primarily in rodents, and implantable devices generally require larger animal models. We recently developed several miniature cardiac bioelectronic devices suitable for mice and rats to enable the advantages of molecular tools and implantable devices to be combined. Successful implementation of these device-enabled studies requires microsurgery approaches that reliably interface bioelectronics to the beating heart with minimal disruption to native physiology. Here we describe how to perform an open thoracic surgical technique for epicardial implantation of wireless cardiac pacemakers in adult rats that has lower mortality than transvenous implantation approaches. In addition, we provide the methodology for a full biocompatibility assessment of the physiological response to the implanted device. The surgical implantation procedure takes ~40 min for operators experienced in microsurgery to complete, and six to eight surgeries can be completed in 1 d. Implanted pacemakers provide programmed electrical stimulation for over 1 month. This protocol has broad applications to harness implantable bioelectronics to enable fully conscious in vivo studies of cardiovascular physiology in transgenic rodent disease models.

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Open thoracic surgical implantation of cardiac pacemakers in rats

Abstract

Bibliographical note

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