Open thoracic surgical implantation of cardiac pacemakers in rats

John A. Rogers, Helen S. Knight, 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, Bender A. Russo, Alexi Kiss, Alejandro Murillo-Berlioz, Tatiana Efimova, Chad R. Haney, Philipp Gutruf, Gregory D. Trachiotis, Igor R. Efimov

Published: 2022-11-20 DOI: 10.1038/s41596-022-00770-y

cardiac pacemakers

implantation surgery

rat models

bioelectronics

physiological response

AI 解读

Extended

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.

Activation of mechanoluminescent nanotransducers by focused ultrasound enables light delivery to deep-seated tissue in vivo

Application of CHyMErA Cas9-Cas12a combinatorial genome-editing platform for genetic interaction mapping and gene fragment deletion screening

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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 rodent
Introduction
Materials
Procedure
Troubleshooting
Timing
Anticipated results
References
ACKNOWLEDGMENTS

Mor, M. et al. Speckle-tracking echocardiography elucidates the effect of pacing site on left ventricular synchronization in the normal and infarcted rat myocardium. PLoS ONE 9, e99191 (2014).
Recchia, F. A. & Lionetti, V. Animal models of dilated cardiomyopathy for translational research. Vet. Res. Commun. 31, 35–41 (2007).
Camacho, P., Fan, H., Liu, Z. & He, J.-Q. Small mammalian animal models of heart disease. Am. J. Cardiovasc. Dis. 6, 70–80 (2016).
Klocke, R., Tian, W., Kuhlmann, M. T. & Nikol, S. Surgical animal models of heart failure related to coronary heart disease. Cardiovasc. Res. 74, 29–38 (2007).
Vaseghi, M. & Shivkumar, K. The role of the autonomic nervous system in sudden cardiac death. Prog. Cardiovasc. Dis. 50, 404–419 (2008).
Schrickel, J. W. et al. Induction of atrial fibrillation in mice by rapid transesophageal atrial pacing. Basic Res. Cardiol. 97, 452–460 (2002).
Nyns, E. C. A. et al. An automated hybrid bioelectronic system for autogenous restoration of sinus rhythm in atrial fibrillation. Sci. Transl. Med. 11, 1–12 (2019).
Berul, C. I., Aronovitz, M. J., Wang, P. J. & Mendelsohn, M. E. In vivo cardiac electrophysiology studies in the mouse. Circulation 94, 2641–2648 (1996).
Lujan, H. L. & DiCarlo, S. E. Cardiac electrophysiology and the susceptibility to sustained ventricular tachycardia in intact, conscious mice. Am. J. Physiol. Circ. Physiol. 306, H1213–H1221 (2014).
Ståhlberg, M. et al. Chronic atrial and ventricular pacing in the mouse: application to model cardiac dyssynchrony and resynchronization in heart failure. Circ. Hear. Fail. 12, 1–11 (2019).
Klapper-Goldstein, H. et al. An implantable system for long-term assessment of atrial fibrillation substrate in unanesthetized rats exposed to underlying pathological conditions. Sci. Rep. 10, 553 (2020).
Gutruf, P. et al. Wireless, battery-free, fully implantable multimodal and multisite pacemakers for applications in small animal models. Nat. Commun. 10, 5742 (2019).
Choi, Y. S. et al. Fully implantable and bioresorbable cardiac pacemakers without leads or batteries. Nat. Biotechnol. https://doi.org/10.1038/s41587-021-00948-x (2021).
Wengrowski, A. M., Kuzmiak-Glancy, S., Jaimes, R. & Kay, M. W. NADH changes during hypoxia, ischemia, and increased work differ between isolated heart preparations. Am. J. Physiol. Circ. Physiol. 306, H529–H537 (2014).
Moreno, A., Kowalik, G., Mendelowitz, D. & Kay, M. W. Optogenetic control of cardiac autonomic neurons in transgenic mice. Methods Mol. Biol. 2191, 309–321 (2021).
Yang, Q. et al. Photocurable, bioresorbable adhesives as functional interfaces between flexible bioelectronic devices and soft biological tissues. Nat. Mater. https://doi.org/10.1038/s41563-021-01051-x (2021).
Choi, Y. S. et al. A transient, closed-loop network of wireless, body-integrated devices for autonomous electrotherapy. Science 376, 1006–1012 (2022).
deAlmeida, A. C., van Oort, R. J. & Wehrens, X. H. T. T. Transverse aortic constriction in mice. J. Vis. Exp. https://doi.org/10.3791/1729 (2010).
Michael, L. H. et al. Myocardial ischemia and reperfusion: a murine model. Am. J. Physiol. Circ. Physiol. 269, H2147–H2154 (1995).
George, S. A. et al. p38δ genetic ablation protects female mice from anthracycline cardiotoxicity. Am. J. Physiol. Circ. Physiol. 319, H775–H786 (2020).
Lee, H., Yoon, D. E. & Kim, K. Genome editing methods in animal models. Anim. Cells Syst. 24, 8–16 (2020).
Obaid, S. N. et al. Multifunctional flexible biointerfaces for simultaneous colocalized optophysiology and electrophysiology. Adv. Funct. Mater. 30, 1910027 (2020).
Chen, Z. et al. Flexible and transparent metal nanowire microelectrode arrays and interconnects for electrophysiology, optogenetics, and optical mapping. Adv. Mater. Technol. 6, 2100225 (2021).
Chen, Z. et al. Flexible and transparent metal oxide/metal grid hybrid interfaces for electrophysiology and optogenetics. Adv. Mater. Technol. 5, 2000322 (2020).
Laughner, J. I. et al. A fully implantable pacemaker for the mouse: from battery to wireless power. PLoS ONE 8, e76291 (2013).
Bilchick, K. C. et al. Differential regional gene expression from cardiac dyssynchrony induced by chronic right ventricular free wall pacing in the mouse. Physiol. Genomics 26, 109–115 (2006).
Sridharan, D. et al. A one-stop protocol to assess myocardial fibrosis in frozen and paraffin sections. Methods Protoc. 5, 13 (2022).
Cardiac Bioelectric Therapy: Mechanisms and Practical Implications (Springer, 2021).
Fishbein, M. C. et al. Cardiac pathology of transvenous pacemakers in dogs. Am. Heart J. 93, 73–81 (1977).
Bowman, T. A. & Hughes, H. C. Swine as an in vivo model for electrophysiologic evaluation of cardiac pacing parameters. Pacing Clin. Electrophysiol. 7, 187–194 (1984).
Wijffels, M. C. E. F., Kirchhof, C. J. H. J., Dorland, R. & Allessie, M. A. Atrial fibrillation begets atrial fibrillation. Circ. J. 92, 1954–1968 (1995).
Vuolteenaho, O., Ala-Kopsala, M. & Ruskoaho, H. BNP as a biomarker in heart disease. Adv. Clin. Chem. 40, 1–36 (2005).
Watson, L. E., Sheth, M., Denyer, R. F. & Dostal, D. E. Baseline echocardiographic values for adult male rats. J. Am. Soc. Echocardiogr. 17, 161–167 (2004).

Open thoracic surgical implantation of cardiac pacemakers in rats

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