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A Model of Sequential Heart and Composite Tissue Allotransplant in Rats

Yang, Jun M.D.; Erdmann, Detlev M.D., Ph.D., M.H.Sc.; Chang, J. C. M.D.; Komatsu, Issei M.D.; Zhang, YiXin M.D.; Wang, DanRu M.D.; Hodavance, Michael S. B.S.; Hollenbeck, Scott T. M.D.; Levinson, Howard M.D.; Klitzman, Bruce Ph.D.; Levin, L. S. M.D.

Plastic & Reconstructive Surgery: July 2010 - Volume 126 - Issue 1 - pp 80-86
doi: 10.1097/PRS.0b013e3181dbbb64
Experimental: Original Articles

Background: Some of the 600,000 patients with solid organ allotransplants need reconstruction with a composite tissue allotransplant, such as the hand, abdominal wall, or face. The aim of this study was to develop a rat model for assessing the effects of a secondary composite tissue allotransplant on a primary heart allotransplant.

Methods: Hearts of Wistar Kyoto rats were harvested and transplanted heterotopically to the neck of recipient Fisher 344 rats. The anastomoses were performed between the donor brachiocephalic artery and the recipient left common carotid artery, and between the donor pulmonary artery and the recipient external jugular vein. Recipients received cyclosporine A for 10 days only. Heart rate was assessed noninvasively. The sequential composite tissue allotransplant consisted of a 3 × 3-cm abdominal musculocutaneous flap harvested from Lewis rats and transplanted to the abdomen of the heart allotransplant recipients. The abdominal flap vessels were connected to the femoral vessels. No further immunosuppression was administered following the composite tissue allotransplant. Ten days after composite tissue allotransplantation, rejection of the heart and abdominal flap was assessed histologically.

Results: The rat survival rate of the two-stage transplant surgery was 80 percent. The transplanted heart rate decreased from 150 ± 22 beats per minute immediately after transplant to 83 ± 12 beats per minute on day 20 (10 days after stopping immunosuppression).

Conclusions: This sequential allotransplant model is technically demanding. It will facilitate investigation of the effects of a secondary composite tissue allotransplant following primary solid organ transplantation and could be useful in developing future immunotherapeutic strategies.

Durham N.C.; Shanghai, China; and Hualien, Taiwan

From the Divisions of Plastic, Reconstructive, Maxillofacial, and Oral Surgery, Orthopedic Surgery, and Cardiothoracic Surgery, Duke University Medical Center; Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Buddhist Tzu Chi General Hospital; and Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University.

Received for publication June 17, 2009; accepted January 7, 2010.

Disclosure: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this article.

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Bruce Klitzman, Ph.D., Kenan Plastic Surgery Research Laboratories, Duke University Medical Center, Durham, N.C. 27710, klitz@duke.edu

©2010American Society of Plastic Surgeons