Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Protocol
  • Published:

A practical guide to setting up pig models for cardiovascular catheterization, electrophysiological assessment and heart disease research

Lab Animal volume 51, pages 46–67 (2022)Cite this article

Subjects

Abstract

Over the past years, the use of large animals has become increasingly interesting in translational research, to bridge the gap between basic research in rodents and targeted therapies in humans. Pigs are highly valued in cardiovascular research because of their anatomical, hemodynamic and electrophysiological features, which closely resemble those of humans. For studying these aspects in swine, cardiac catheterization techniques are essential procedures. Although cardiac catheterization seems to be comparatively easy in pigs as human equipment can be used to perform the procedure, there are some pitfalls. Here we provide a detailed protocol to guide the reader through different aspects of cardiac catheterization in pigs. We suggest an approach for safe intubation and extubation, provide tips for perioperative and postoperative management of the animals and guide the reader through different experimental steps, including sheath insertion. We also describe the procedures for basic electrophysiological assessment of conduction properties and atrial fibrillation induction, hemodynamic assessment via pressure–volume loops, right heart and left heart catheterization and the development of a myocardial infarction model by balloon occlusion. This protocol was developed in Landrace pigs and can be adapted to other pig breeds or other large animal species. This protocol requires approximately six and a half working hours in total and should be performed by researchers with previous experience in large animal experimentation and in the presence of a veterinarian.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Overview of equipment needed for intubation and illustration of the intubation technique in ventral and dorsal recumbency.
Fig. 2: Illustration of venous and arterial cervical sheath insertion.
Fig. 3: Overview of the stages for successful PV loop generation.
Fig. 4: Overview of instruments and equipment used for cardiac catheterization and electrophysiology studies.

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385, 117–171 (2015).

  2. Mensah, G. A. et al. Decline in cardiovascular mortality: possible causes and implications. Circ. Res. 120, 366–380 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rossello, X., Pocock, S. J. & Julian, D. G. Long-term use of cardiovascular drugs: challenges for research and for patient care. J. Am. Coll. Cardiol. 66, 1273–1285 (2015).

    Article  CAS  PubMed  Google Scholar 

  4. Vegter, E. L. et al. Rodent heart failure models do not reflect the human circulating microRNA signature in heart failure. PLoS ONE 12, e0177242 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Clauss, S. et al. Animal models of arrhythmia: classic electrophysiology to genetically modified large animals. Nat. Rev. Cardiol. 16, 457–475 (2019).

    Article  PubMed  Google Scholar 

  6. Ginis, I. et al. Differences between human and mouse embryonic stem cells. Dev. Biol. 269, 360–380 (2004).

    Article  CAS  PubMed  Google Scholar 

  7. Haghighi, K. et al. Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human. J. Clin. Invest. 111, 869–876 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schuttler, D. et al. Animal models of atrial fibrillation. Circ. Res. 127, 91–110 (2020).

    Article  PubMed  CAS  Google Scholar 

  9. Jinek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816–821 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Watanabe, M. & Nagashima, H. Genome editing of pig. Methods Mol. Biol. 1630, 121–139 (2017).

    Article  CAS  PubMed  Google Scholar 

  11. Neff, E. P. Cancer modeling thinks big with the pig. Lab Anim. (NY) 48, 75–78 (2019).

    Article  Google Scholar 

  12. Walters, E. M., Wells, K. D., Bryda, E. C., Schommer, S. & Prather, R. S. Swine models, genomic tools and services to enhance our understanding of human health and diseases. Lab Anim. (NY) 46, 167–172 (2017).

    Article  Google Scholar 

  13. Renner, S. et al. Permanent neonatal diabetes in INS(C94Y) transgenic pigs. Diabetes 62, 1505–1511 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Park, D. S. et al. Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias. J. Clin. Invest. 125, 403–412 (2015).

    Article  PubMed  Google Scholar 

  15. Huang, L. et al. CRISPR/Cas9-mediated ApoE−/− and LDLR−/− double gene knockout in pigs elevates serum LDL-C and TC levels. Oncotarget 8, 37751–37760 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kilkenny, C., Browne, W. J., Cuthill, I. C., Emerson, M. & Altman, D. G. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 8, e1000412 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Lees, P. & Meredith, M. J. in Veterinary Pharmacology and Toxicology. (ed Toutain P. L. Ruckebusch Y., Koritz G. D.) (Springer, Dordrecht, 1983).

  18. Clarke, K. W., Trim, C. M. & Hall, L. W. Veterinary Anaesthesia. 11th Edition edn, (Saunders Elsevier, 2014).

  19. Lee, J. Y. & Kim, M. C. Anesthesia of growing pigs with tiletamine–zolazepam and reversal with flumazenil. J. Vet. Med. Sci. 74, 335–339 (2012).

    Article  CAS  PubMed  Google Scholar 

  20. Gomez de Segura, I. A. et al. Actions of xylazine in young swine. Am. J. Vet. Res. 58, 99–102 (1997).

    CAS  PubMed  Google Scholar 

  21. Steinbacher, R., von Ritgen, S. & Moens, Y. P. Laryngeal perforation during a standard intubation procedure in a pig. Lab Anim. 46, 261–263 (2012).

    Article  CAS  PubMed  Google Scholar 

  22. Chum, H. & Pacharinsak, C. Endotracheal intubation in swine. Lab Anim. (NY) 41, 309–311 (2012).

    Article  Google Scholar 

  23. Huh, H. et al. A novel and simple method for tracheal intubation in a swine model: preparing for the era of xenotransplantation. Exp. Clin. Transplant. 15, 453–457 (2017).

    PubMed  Google Scholar 

  24. Duke-Novakovski, T., Ambros, B., Auckland, C. D. & Harding, J. C. The effects of succinylcholine or low-dose rocuronium to aid endotracheal intubation of adult sows. Can. J. Vet. Res. 76, 57–61 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Pehbock, D. et al. Anesthesia in swine: optimizing a laboratory model to optimize translational research. Anaesthesist 64, 65–70 (2015).

    Article  CAS  PubMed  Google Scholar 

  26. Houde, A., Pommier, S. A. & Roy, R. Detection of the ryanodine receptor mutation associated with malignant hyperthermia in purebred swine populations. J. Anim. Sci. 71, 1414–1418 (1993).

    Article  CAS  PubMed  Google Scholar 

  27. Lindgren, L., Saarnivaara, L. & Klemola, U. M. Protection by fentanyl against cardiac dysrhythmias during induction of anaesthesia. Eur. J. Anaesthesiol. 4, 229–233 (1987).

    CAS  PubMed  Google Scholar 

  28. Rizas, K. D. et al. Sympathetic activity-associated periodic repolarization dynamics predict mortality following myocardial infarction. J. Clin. Invest. 124, 1770–1780 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nearing, B. D. & Verrier, R. L. Tracking cardiac electrical instability by computing interlead heterogeneity of T-wave morphology. J. Appl. Physiol. 95, 2265–2272 (2003).

    Article  PubMed  Google Scholar 

  30. Silverman, J. & Muir, W. W. 3rd A review of laboratory animal anesthesia with chloral hydrate and chloralose. Lab Anim. Sci. 43, 210–216 (1993).

    CAS  PubMed  Google Scholar 

  31. Beam, D. M. et al. Comparison of isoflurane and alpha-chloralose in an anesthetized swine model of acute pulmonary embolism producing right ventricular dysfunction. Comp. Med. 65, 54–61 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Walther, A. & Bardenheuer, H. J. [Intraoperative administration of calcium. Physiology–physiopathology–clinical indications]. Anaesthesist 47, 339–347 (1998).

    Article  CAS  PubMed  Google Scholar 

  33. Black, W. D. Veterinary drug handbook. Can. Vet. J. 44, 297 (2003).

    PubMed Central  Google Scholar 

  34. Clarke, K. W. Desflurane and sevoflurane: new volatile anesthetic agents. V. Clin. North Am. Small Anim. Pract. 29, 793–810 (1999).

    Article  CAS  Google Scholar 

  35. Hikasa, Y., Ohe, N., Takase, K. & Ogasawara, S. Cardiopulmonary effects of sevoflurane in cats: comparison with isoflurane, halothane, and enflurane. Res. Vet. Sci. 63, 205–210 (1997).

    Article  CAS  PubMed  Google Scholar 

  36. Monk, J. P., Beresford, R. & Ward, A. Sufentanil. A review of its pharmacological properties and therapeutic use. Drugs 36, 286–313 (1988).

    Article  CAS  PubMed  Google Scholar 

  37. Cavanagh, K. Plumb’s veterinary drug handbook. Pocket—7th edition. Can. Vet. J. 53, 1284–1284 (2012).

    PubMed Central  Google Scholar 

  38. Harvey-Clark, C. J., Gilespie, K. & Riggs, K. W. Transdermal fentanyl compared with parenteral buprenorphine in post-surgical pain in swine: a case study. Lab Anim. 34, 386–398 (2000).

    Article  CAS  PubMed  Google Scholar 

  39. Erhardt, W., Henke, J., Haberstroh, J., Baumgartner, C. & Tacke, S. Anästhesie und Analgesie beim Klein- und Heimtier (Schattauer, 2012).

  40. Henke, J. et al. (ed Fachinformation aus dem Ausschuss für Anästhesie der GV-SOLAS in Zusammenarbeit mit dem Arbeitskreis 4 in der TVT: Schmerztherapie bei Versuchstieren) (2015).

  41. Rodriguez, N. A., Cooper, D. M. & Risdahl, J. M. Antinociceptive activity of and clinical experience with buprenorphine in swine. Contemp. Top Lab. Anim. Sci. 40, 17–20 (2001).

    CAS  PubMed  Google Scholar 

  42. Birkholz, T. et al. Influence of cardiac output on the pharmacokinetics of sufentanil in anesthetized pigs. Anesthesiology 128, 912–920 (2018).

    Article  CAS  PubMed  Google Scholar 

  43. Lee, A. M. et al. A simple porcine model of inducible sustained atrial fibrillation. Innovations (Phila) 11, 76–78 (2016).

    Article  Google Scholar 

  44. Clauss, S. et al. Characterization of a porcine model of atrial arrhythmogenicity in the context of ischaemic heart failure. PLoS ONE 15, e0232374 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Munz, M. R., Faria, M. A., Monteiro, J. R., Aguas, A. P. & Amorim, M. J. Surgical porcine myocardial infarction model through permanent coronary occlusion. Comp. Med. 61, 445–452 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Kim, W. et al. A porcine model of ischemic heart failure produced by intracoronary injection of ethyl alcohol. Heart Vessels 26, 342–348 (2011).

    Article  PubMed  Google Scholar 

  47. Sakaguchi, G. et al. A pig model of chronic heart failure by intracoronary embolization with gelatin sponge. Ann. Thorac. Surg. 75, 1942–1947 (2003).

    Article  PubMed  Google Scholar 

  48. Bosnjak, M. et al. Pharmacokinetics of carprofen in anaesthetized pigs: a preliminary study. Vet. Anaesth. Analg. 48, 35–41 (2021).

    Article  CAS  PubMed  Google Scholar 

  49. O’Brien, W. M. & Bagby, G. F. Carprofen: a new nonsteroidal antiinflammatory drug. Pharmacology, clinical efficacy and adverse effects. Pharmacotherapy 7, 16–24 (1987).

    Article  PubMed  Google Scholar 

  50. Hendrickson, D. A. & Baird, A. N. Turner and McIlwraith’s Techniques in Large Animal Surgery, 4th Edition. (Wiley-Blackwell, 2013).

  51. Moon, P. F. & Smith, L. J. General anesthetic techniques in swine. Vet. Clin. North Am. Food Anim. Pract. 12, 663–691 (1996).

    Article  CAS  PubMed  Google Scholar 

  52. Bollen, P., K. Hansen, A. & Olsen Alstrup, A. The Laboratory Swine (Boca Raton: CRC Press, 2000).

  53. Bollen, P. & Ellegaard, L. The Gottingen minipig in pharmacology and toxicology. Pharmacol. Toxicol. 80, 3–4 (1997).

    Article  CAS  PubMed  Google Scholar 

  54. Rozkot, M., Václavková, E. & Bělková, J. Minipigs as labaratory animals—Review. Res. Pig Breeding 9, 10–15 (2015).

    Google Scholar 

  55. Beglinger, R. & Becker, M. in Das Göttinger Miniaturschwein (eds P. Glodek & B. Oldigs) 75–85 (Paul Parey, 1982).

  56. Duval, J. D., Pang, J. M., Boysen, S. R. & Caulkett, N. A. Cardiopulmonary effects of a partial intravenous anesthesia technique for laboratory swine. J. Am. Assoc. Lab. Anim. Sci. 57, 376–381 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Sharp, T. E. 3rd et al. Novel Gottingen miniswine model of heart failure with preserved ejection fraction integrating multiple comorbidities. JACC Basic Transl. Sci. 6, 154–170 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Smith, A. C., Spinale, F. G. & Swindle, M. M. Cardiac function and morphology of Hanford miniature swine and Yucatan miniature and micro swine. Lab. Anim. Sci. 40, 47–50 (1990).

    CAS  PubMed  Google Scholar 

  59. Lelovas, P. P., Kostomitsopoulos, N. G. & Xanthos, T. T. A comparative anatomic and physiologic overview of the porcine heart. J. Am. Assoc. Lab. Anim. Sci. 53, 432–438 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Clutton, R. E., Blissitt, K. J., Bradley, A. A. & Camburn, M. A. Comparison of three injectable anaesthetic techniques in pigs. Vet. Rec. 141, 140–146 (1997).

    Article  CAS  PubMed  Google Scholar 

  61. Santos, M., Bertran de Lis, B. T. & Tendillo, F. J. Effects of intramuscular dexmedetomidine in combination with ketamine or alfaxalone in swine. Vet. Anaesth. Analg. 43, 81–85 (2016).

    Article  CAS  PubMed  Google Scholar 

  62. Bustamante, R. & Valverde, A. Determination of a sedative dose and influence of droperidol and midazolam on cardiovascular function in pigs. Can. J. Vet. Res. 61, 246–250 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Ko, J. C., Williams, B. L., Smith, V. L., McGrath, C. J. & Jacobson, J. D. Comparison of telazol, telazol–ketamine, telazol–xylazine, and telazol–ketamine–xylazine as chemical restraint and anesthetic induction combination in swine. Lab. Anim. Sci. 43, 476–480 (1993).

    CAS  PubMed  Google Scholar 

  64. Henrikson, H., Jensen-Waern, M. & Nyman, G. Anaesthetics for general anaesthesia in growing pigs. Acta Vet. Scand. 36, 401–411 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lee, J. Y., Jee, H. C., Jeong, S. M., Park, C. S. & Kim, M. C. Comparison of anaesthetic and cardiorespiratory effects of xylazine or medetomidine in combination with tiletamine/zolazepam in pigs. Vet. Rec. 167, 245–249 (2010).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) grant number 413635475 and the Munich Clinician Scientist Program (MCSP) of the LMU Munich to D.S. and P.T., the German Centre for Cardiovascular Research (DZHK; 81X2600255 to S.C.; 81Z0600206 to S.K.), the Corona Foundation (S199/10079/2019 to S.C.), the ERA-NET on Cardiovascular Diseases (ERA-CVD; 01KL1910 to S.C.) and the Heinrich-and-Lotte-Mühlfenzl Stiftung (to S.C.). The funders had no role in manuscript preparation.

Author information

Author notes

  1. These authors contributed equally: Dominik Schüttler, Philipp Tomsits, Christina Bleyer.

Authors and Affiliations

  1. Medizinische Klinik und Poliklinik I, LMU Hospital, Ludwig-Maximilians-Universität Munich (LMU), Munich, Germany

    Dominik Schüttler, Philipp Tomsits, Christina Bleyer, Julia Vlcek, Valerie Pauly, Nora Hesse, Moritz Sinner, Stefan Kääb & Sebastian Clauss

  2. DZHK (German Centre for Cardiovascular Research), Partner Site Munich, Munich Heart Alliance (MHA), Munich, Germany

    Dominik Schüttler, Philipp Tomsits, Christina Bleyer, Valerie Pauly, Nora Hesse, Moritz Sinner, Daphne Merkus, Jules Hamers, Stefan Kääb & Sebastian Clauss

  3. Institute of Surgical Research at the Walter-Brendel-Centre of Experimental Medicine, LMU Hospital, Ludwig-Maximilians-Universität Munich (LMU), Munich, Germany

    Dominik Schüttler, Philipp Tomsits, Christina Bleyer, Julia Vlcek, Valerie Pauly, Nora Hesse, Daphne Merkus, Jules Hamers & Sebastian Clauss

  4. Division of Experimental Cardiology, Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands

    Daphne Merkus

Authors
  1. Dominik Schüttler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philipp Tomsits
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christina Bleyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Julia Vlcek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Valerie Pauly
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nora Hesse
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Moritz Sinner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Daphne Merkus
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jules Hamers
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Stefan Kääb
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sebastian Clauss
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.S., P.T. and S.C. drafted the manuscript and prepared the figures. C.B., J.V., V.P. and N.H. wrote the sections ‘Materials’, ‘Equipment’, ‘Reagent setup’ and ‘Equipment setup’ and prepared Tables 1–3. M.S. wrote the section ‘Sonography-guided puncture of the femoral vessels’. D.M. and J.H. wrote the section ‘PV loops’. S.K. wrote the section ‘Coronary angiography’. All authors carefully read and revised the manuscript.

Corresponding author

Correspondence to Sebastian Clauss.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Lab Animal thanks the anonymous reviewers for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schüttler, D., Tomsits, P., Bleyer, C. et al. A practical guide to setting up pig models for cardiovascular catheterization, electrophysiological assessment and heart disease research. Lab Anim 51, 46–67 (2022). https://doi.org/10.1038/s41684-021-00909-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41684-021-00909-6

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing