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Refinement of in vivo surgical procedures for cardiac gene and cell transfer in rats

Lab Animal volume 38, pages 94–101 (2009)Cite this article

Abstract

In studies of gene and cell transfer for the treatment of heart disease, direct intramyocardial injection and antegrade intracoronary injection are common methods of delivering biomaterials to the heart. The authors, who carried out these surgical procedures in 377 rats, describe their methodology in detail and discuss surgical refinements that substantially reduced rat mortality. These refinements include a rigorous fluid replacement regimen, use of inhalational anesthesia instead of injectable agents, exposure of the heart without direct contact and use of a chest drainage cannula to remove air from the pleural cavity and prevent lung collapse.

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Figure 1: Standard ICI procedure.
Figure 2: Effects of procedural modifications on mortality during direct injection.
Figure 3: Effects of procedural modifications on mortality during ICI.

References

  1. Sato, M., O'Gara, P., Harding, S.E. & Fuller, S.J. Enhancement of adenoviral gene transfer to adult rat cardiomyocytes in vivo by immobilisation and ultrasound treatment of the heart. Gene Ther. 12, 936–941 (2005).

    Article  CAS  Google Scholar 

  2. Hajjar, R.J. et al. Modulation of ventricular function through gene transfer in vivo. Proc. Natl. Acad. Sci. USA 95, 5251–5256 (1998).

    Article  CAS  Google Scholar 

  3. Muhlhauser, J. et al. Safety and efficacy of in vivo gene transfer into the porcine heart with replication-deficient, recombinant adenovirus vectors. Gene Ther. 3, 145–153 (1996).

    CAS  Google Scholar 

  4. Logeart, D. et al. Highly efficient adenovirus-mediated gene transfer to cardiac myocytes after single-pass coronary delivery. Hum. Gene Ther. 11, 1015–1022 (2000).

    Article  CAS  Google Scholar 

  5. Wright, M.J., Wightman, L.M.L., Latchman, D.S. & Marber, M.S. In vivo myocardial gene transfer: optimization and evaluation of intracoronary gene delivery in vivo. Gene Ther. 8, 1833–1839 (2001).

    Article  CAS  Google Scholar 

  6. Donahue, J.K., Kikkawa, K., Thomas, A.D., Marban, E. & Lawrence, J.H. Acceleration of widespread adenoviral gene transfer to intact rabbit hearts by coronary perfusion with low calcium and serotonin. Gene Ther. 5, 630–634 (1998).

    Article  CAS  Google Scholar 

  7. Shohet, R.V. et al. Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium. Circulation 101, 2554–2556 (2000).

    Article  CAS  Google Scholar 

  8. Ronen, B. et al. New efficient catheter-based system for myocardial gene delivery. Circulation 106, 1756–1759 (2002).

    Article  Google Scholar 

  9. Nicklas, W. et al. Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Lab. Anim. 36, 20–43 (2002).

    Article  CAS  Google Scholar 

  10. Home Office. Code of Practice for the housing and care of animals used in scientific procedures (HMSO, London, 1996).

  11. Campbell, I.T., Baxter, J.N., Tweedie, I.E., Taylor, G.T. & Keens, S.J. IV fluids during surgery. Br. J. Anaesth. 65, 726–729 (1990).

    Article  CAS  Google Scholar 

  12. Flecknell, P.A., Liles, J.H. & Wootton, R. Reversal of fentanyl/fluanisone neuroleptanalgesia in the rabbit using mixed agonist/antagonist opioids. Lab. Anim. 23, 147–155 (1989).

    Article  CAS  Google Scholar 

  13. Prentice, R.L. & Kalbfleisch, J.D. Hazard rate models with covariates. Biometrics 35, 25–39 (1979).

    Article  CAS  Google Scholar 

  14. Clary, E.M., O'Halloran, E.K., de la Fuente, S.G. & Eubanks, S. Videoendoscopic endotracheal intubation of the rat. Lab. Anim. 38, 158–161 (2004).

    Article  CAS  Google Scholar 

  15. Guzman, R.J., Lemarchand, P., Crystal, R.G., Epstein, S.E. & Finkel, T. Efficient gene transfer into myocardium by direct injection of adenovirus vectors. Circ. Res. 73, 1202–1207 (1993).

    Article  CAS  Google Scholar 

  16. Kitsis, R.N., Buttrick, P.M., McNally, E.M., Kaplan, M.L. & Leinwand, L.A. Hormonal regulation of a gene injected into rat heart in vivo. Proc. Natl. Acad. Sci. USA 88, 4138–4142 (1991).

    Article  CAS  Google Scholar 

  17. Hanley, P.J. & Loiselle, D.S. Mechanisms of force inhibition by halothane and isoflurane in intact rat cardiac muscle. J. Physiol. 506, 231–244 (1998).

    Article  CAS  Google Scholar 

  18. Frank, S.M. et al. Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events. A randomized clinical trial. JAMA 277, 1127–1134 (1997).

    Article  CAS  Google Scholar 

  19. Leslie, K., Sessler, D.I., Bjorkstern, A.R. & Moayeri, A. Mild hypothermia alters propofol pharmacokinetics and increases the duration of action of atracurium. Anesth. Analg. 80, 1007–1014 (1995).

    CAS  Google Scholar 

  20. Caldwell, J.E. et al. Temperature-dependent pharmacokinetics and pharmacodynamics of vecuronium. Anesthesiology 92, 84–93 (2000).

    Article  CAS  Google Scholar 

  21. Lenhardt, R. et al. Mild intraoperative hypothermia prolongs postanesthestic recovery. Anesthesiology 87, 1318–1323 (1997).

    Article  CAS  Google Scholar 

  22. Schmied, H., Kurz, A., Sessler, D.I., Kozek, S. & Reiter, A. Mild hypothermia increases blood loss and transfusion requirements during total hip arthroplasty. Lancet 347, 289–292 (1996).

    Article  CAS  Google Scholar 

  23. Kurz, A., Sessler, D.I. & Lenhardt, R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N. Engl. J. Med. 334, 1209–1215 (1996).

    Article  CAS  Google Scholar 

  24. Gal, D. et al. Direct myocardial transfection in two animal models: Evaluation of parameters affecting gene expression and percutaneous gene delivery. Lab. Invest. 68, 18–25 (1993).

    CAS  Google Scholar 

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Acknowledgements

We thank Central Biomedical Services, Royal Brompton for technical support.

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Authors and Affiliations

  1. Cardiovascular Science Royal Brompton Campus, Imperial College, Guy Scadding Building, Dovehouse St., London, SW3 6LY, UK

    Motoki Sato &  Sian E. Harding

  2. Central Biomedical Services, Imperial College Charing Cross Campus, St. Dunstan's Road, London, W6 8RP, UK

    Angela Kerton

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  1. Motoki Sato
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  3. Sian E. Harding
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Correspondence to Sian E. Harding.

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The authors declare no competing financial interests.

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Sato, M., Kerton, A. & Harding, S. Refinement of in vivo surgical procedures for cardiac gene and cell transfer in rats. Lab Anim 38, 94–101 (2009). https://doi.org/10.1038/laban0309-94

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