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Open thoracic surgical implantation of cardiac pacemakers in rats


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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Fig. 1: Overview of surgical implantation of wireless battery-free miniature pacemakers in rodents.
Fig. 2: Surgical space setup.
Fig. 3: Intubation technique for open thoracic approach and surgical table preparations before incision.
Fig. 4: Pacemaker implantation technique for attachment to ventricles.
Fig. 5: Pacemaker implantation technique for attachment to right atrium.
Fig. 6: Physiological effects of pacemaker implantation surgery.
Fig. 7: Long-term in vivo pacing following pacemaker implantation.

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Data availability

The raw data that support the results in Fig. 6b–g, Extended Data Fig. 1 and Supplementary Figs. 16 can be found in Supplementary Information.

Code availability

Our custom MATLAB software for quantification of our Masson’s trichrome histology images can be downloaded for free at Github:


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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.

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Authors and Affiliations



R.T.Y., S.W.C., K.B.L. and I.R.E. led the development of the concepts, designed the experiments and interpreted results. S.W.C., K.B.L., M.A.N., T.J.H., J.B.L. and A.M.-B. performed the surgeries. Y.S.C., J.K., J.A., P.G. and J.A.R. developed fabrication methods and devices. Q.Y. created the bioadhesive and adhesion strategy. R.T.Y. and G.K. completed preoperative and postoperative care of animals. E.A.W., A.B. and C.R.H. performed magnetic resonance imaging scans and image segmentation. R.T.Y., A.N.M., H.S.K. and B.A.R. completed histology and echocardiography. R.T.Y. and H.S.K. quantified behavioral monitoring of rats. R.T.Y., H.S.K., B.A.R., A.K. and T.E. devised and performed ELISA biomarker analysis. R.T.Y., S.W.C. and K.B.L. weighed the animals. R.T.Y. completed all ECG recordings and dissections. R.T.Y., S.W.C., K.B.L., M.A.N., T.J.H., G.D.T. and I.R.E. wrote the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Igor R. Efimov.

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Competing interests

J.A.R. is a cofounder of NeuroLux Inc.

Peer review

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Nature Protocols thanks Daniël Pijnappels and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Related links

Key references using this protocol

Gutruf, P. et al. Nat. Commun. 10, 5742 (2019):

Choi, Y. S. et al. Nat. Biotechnol. 39, 1228–1238 (2021):

Yang, Q. et al. Nat. Mater. 20, 1559–1570 (2021):

Extended data

Extended Data Fig. 1 Assessment of surgery time.

a, The surgery workflow timeline is as follows: induction, intubation, incision, closure and extubation. b, For an experienced surgeon performing this procedure, the total time for surgery from induction to extubation is ~43 min, including initiation of anesthesia, intubation, incision, affixation of pacemaker, closure and extubation. Average times for an experienced surgeon to complete each section of the workflow timeline are provided. For operators just beginning to learn this technique, intubation may take several additional attempts. Additional time is required pre- and postoperatively to fulfill responsibilities such as preparation of equipment, retrieval and return of animals to the housing facility, administration of follow-up analgesic doses and recovery observation.

Source data

Extended Data Fig. 2 Open thoracic implantation technique for biventricular pacemaker implantation.

a, Electrodes of biventricular pacemaker positioned onto ventricle of Langendorff-perfused mouse heart. Scale bar, 5 mm. b, Electrodes of the biventricular pacemaker sutured onto left and right ventricles during implantation surgery. Scale bar, 5 mm. c, Anterior and d, cross-sectional CT visualization of the biventricular pacemaker placed within a rat’s anatomy.

Extended Data Fig. 3 Implantation of miniature battery-free wireless pacemakers using hydrogel adhesive.

a, This technique allows for pacemakers to be attached with adhesives. Following opening of the chest, the pacemaker is affixed to the epicardial surface of the ventricles with a soft injectable bioadhesive. UV light is used to illuminate the bioadhesive to cure and secure the electrode pad in place. Scale bar, 5 mm. b, ECG traces of animals implanted with pacemakers were recorded daily postoperation. Pacemakers were able to capture and drive the heart rhythm for up to 8 d postsurgery.

Supplementary information

Supplementary Information

Supplementary Figs. 1–6.

Reporting Summary

Supplementary Data 1

Raw data of surgery mortality rate relating to operator experience

Supplementary Data 2

Raw data on functional lifetime of pacemakers in all rat subjects

Supplementary Data 3

Raw data of systemic assessment of animal behavior, appearance, and reactivity to handling

Supplementary Data 4

Raw data of ELISA assessment of BNP 45 for rats with pacemakers attached to the atrium

Supplementary Data 5

Raw data of ELISA assessment of CK-MB for rats with pacemakers attached to the ventricles

Supplementary Data 6

Raw data of echocardiography parameters (fractional shortening, cardiac output, diastolic volume, diastolic diameter, systolic volume, and systolic diameter)

Source data

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Yin, R.T., Chen, S.W., Benjamin Lee, K. et al. Open thoracic surgical implantation of cardiac pacemakers in rats. Nat Protoc 18, 374–395 (2023).

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