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Method Article

Orthotopic Aortic Transplantation: A Rat Model to Study the Development of Chronic Vasculopathy

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DOI:

10.3791/1989

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December 4th, 2010

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In This Article

Summary

This video demonstrates the orthotopic aortic transplant model as a simple model to study the development of transplant vasculopathy (TVP) in rats.

Abstract

Research models of chronic rejection are essential to investigate pathobiological and pathophysiological processes during the development of transplant vasculopathy (TVP).

The commonly used animal model for cardiovascular chronic rejection studies is the heterotopic heart transplant model performed in laboratory rodents. This model is used widely in experiments since Ono and Lindsey (3) published their technique. To analyze the findings in the blood vessels, the heart has to be sectioned and all vessels have to be measured.

Another method to investigate chronic rejection in cardiovascular questionings is the aortic transplant model (1, 2). In the orthotopic aortic transplant model, the aorta can easily be histologically evaluated (2). The PVG-to-ACI model is especially useful for CAV studies, since acute vascular rejection is not a major confounding factor and Cyclosporin A (CsA) treatment does not prevent the development of CAV, similar to what we find in the clinical setting (4). A7-day period of CsA is required in this model to prevent acute rejection and to achieve long-term survival with the development of TVP.

This model can also be used to investigate acute cellular rejection and media necrosis in xenogeneic models (5).

Protocol

Rats weighing approximately 250-300g are purchased from Charles River (Sandhofer Weg 7, D-97633 Sulzfeld).
Transplants are performed using PVG rats as donors, and ACI rats as recipients.

Rats are housed under conventional conditions, fed standard rat chow and water ad libidum.

All surgical instruments are sterilized prior to use.

Donor preparation:

Anesthetize rat with isoflurane (2,5-3%) using an induction chamber.

  1. Shave the abdominal and thoracic hair and place the rat on its back and place a facemask over its nose and mouth to ke....

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Discussion

For several reasons we found the orthotopic aortic transplantation model a more accurate way to investigate the development of TVP compared to the heterotopic heart transplantation model:
Regarding the surgical technique, the aortic transplant model embodies an easily feasible method, requiring solely the accomplishment of end-to-end-anastomosis, whereas the heterotopic heart transplant model may be considered a more complex and error-prone challenge to the surgeon s skills, requiring end-to-side anastomosis on tw.......

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Disclosures

No conflicts of interest declared.

Acknowledgements

The authors thank Christiane Pahrmann for her histological work.

Funding

Sonja Schrepfer has received a research grant from the Deutsche Forschungsgemeinschaft (DFG) (SCHR992/3 1 and SCHR992/4-1).]

....

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Materials

List of materials used in this article
NameCompanyCatalog NumberComments
Surgical microscope (magnification 25x)
Isoflurane
shaver
Provo-Iodine
ice cold 0.9% saline
prewarmed 0.9% sterile saleine
eye ointment
glove
microsurgical scissirs
forceps
clamps
8-0 suture (prolene)
6-0 suture (prolene)
5-0 suture (prolene)
Carprofen
Metamizol
Q-tips

References

  1. Deuse, T., Hoyt, G., Koyanagi, T., Robbins, R. C., Schrepfer, S. Prevention and Inhibition But Not Reversion of Chronic Allograft Vasculopathy by FK778. Transplantation. 85, 870-877 (2008).
  2. Mennander, A., Tiisala, S., Halttunen, J., Yilmaz, S., Paavonen, T., Hayry, P.

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