Department of Surgery, University of California, San Francisco - UCSF
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Liu, F., Kang, S. M. Heterotopic Heart Transplantation in Mice. J. Vis. Exp. (6), e238, doi:10.3791/238 (2007).
The mouse heterotopic heart transplantation has been used widely since it was introduced by Drs. Corry and Russell in 1973. It is particularly valuable for studying rejection and immune response now that newer transgenic and gene knockout mice are available, and a large number of immunologic reagents have been developed. The heart transplant model is less stringent than the skin transplant models, although technically more challenging. We have developed a modified technique and have completed over 1000 successful cases of heterotopic heart transplantation in mice. When making anastomosis of the ascending aorta and abdominal aorta, two stay sutures are placed at the proximal and distal apexes of recipient abdominal aorta with the donor s ascending aorta, then using 11-0 suture for anastomosis on both side of aorta with continuing sutures. The stay sutures make the anastomosis easier and 11-0 is an ideal suture size to avoid bleeding and thrombosis.
When making anastomosis of pulmonary artery and inferior vena cava, two stay sutures are made at the proximal apex and distal apex of the recipient s inferior vena cava with the donor s pulmonary artery. The left wall of the inferior vena cava and donor s pulmonary artery is closed with continuing sutures in the inside of the inferior vena cava after, one knot with the proximal apex stay suture the right wall of the inferior vena cava and the donor s pulmonary artery are closed with continuing sutures outside the inferior vena cave with 10-0 sutures. This method is easier to perform because anastomosis is made just on the one side of the inferior vena cava and 10-0 sutures is the right size to avoid bleeding and thrombosis. In this article, we provide details of the technique to supplement the video.
Donor Preparation and Heart Harvest:
Recipient Preparation and Transplantation
We have successfully performed more than 1000 cases of heterotopic heart transplantation in mice and achieved over 90% success rate in different strains of mice, including wild type, transgenic and gene knockout mice.
Since Drs. Corry and Russell introduced heterotopic heart transplantation in mice in 1973, this model has proven to be a particularly valuable for studying immune rejection response and developing novel immunosuppressive strategies. This model can be used more broadly now because the emergence of numerous transgenic and gene knockout mice has provided new ways to study the mechanisms of rejection/tolerance. The vascularized heart transplant model may be more relevant to clinical solid organ transplantation. Although skin transplants or subcutaneous transplants of neonatal hearts are technically simpler, the neovascularization that is required for graft survival in these transplants are particularly sensitive to allogenic responses. Thus, skin and subcutaneous hear transplants can be useful for a stringent test of tolerance, but not for the development or optimization of immunosuppressive or tolerance inducing protocols.
We modified the vascular heart transplant technique in several ways to improve efficiency and success rates:
Although the technique of heterotopic heart transplantation in mice is technically challenging, it is an important technique for studying alloresponses. Practice and technical modifications have resulted in a successful rate of over 90% in our laboratory. We believe that the video and the accompanying manuscript will help to lessen the learning curve for laboratories that wish to use this technique.
1. Robert J. Corry, Henry J. Winn, and Paul S. Russell. Primarily vascularized allografts of heart in mice. Transplantation. Vol. 16, No4, 343-350(1973).