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J Thorac Cardiovasc Surg 2001;121:0241-0248
© 2001 The American Association for Thoracic Surgery

General Thoracic Surgery

Feasibility of cryopreserved tracheal xenotransplants with the use of short-course immunosuppression

Mitsunori Hashimoto, MD, Ryoichi Nakanishi, MD, Masayoshi Umesue, MD, Hiroyuki Muranaka, MD, Mitsuhiro Hachida, MD, Kosei Yasumoto, MD

From the Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.

This study was supported by a Research Grant for Immunology, Allergy and Organ Transplant, Ministry of Health and Welfare, and Grant-in-Aid 08671555 from the Ministry of Education, Science, and Culture of Japan.

Received for publication April 17, 2000. Revisions requested July 21, 2000; revisions received Aug 31, 2000. Accepted for publication Sept 29, 2000. Address for reprints: Ryoichi Nakanishi, MD, Assistant Professor, Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan (E-mail: ryoichi{at}med.uoeh-u.ac.jp).

Objective: We evaluated the feasibility of discordant xenotransplantation of the cryopreserved trachea with intermittent immunosuppression to help solve the shortage of donor tracheas.
Methods: Two experiments were performed with heterotopic transplantation models in 14 guinea pigs and 85 rats. So that the minimal dose of FK506 for viable fresh xenografts could be determined, FK506 was given in escalating doses (0, 1.5, 2.5, and 3.5 mg/kg) for recipient animals after xenogeneic transplantation. With the goal of obtaining a long-term survival of the xenografts, the effect of cryopreservation on xenografts was assessed and thereafter different cycles of immunosuppression every third week were evaluated in fresh or cryopreserved xenografts in the second experiment.
Results: An FK506 dosage of more than 2.5 mg/kg per day was much more effective than smaller dosages, as demonstrated by morphologic assessment. A higher dosage of FK506 potentially delayed the rejection of xenografts and can thus maintain tracheal xenograft viability for less than 4 weeks in rat recipients. In experiment 2, the cryopreserved xenografts showed less histologic viability than fresh xenografts but greater patency of the lumen. The patency of cryopreserved xenografts was favorably maintained for a longer period than that of fresh xenografts with either the same number or more cycles of immunosuppression.
Conclusions: We conclude that the synergistic effect of cryopreservation and adequate intermittent immunosuppression may enable tracheal xenografts to remain viable over longer periods.






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