Canine laryngeal transplantation: preliminary studies and a new heterotopic allotransplantation model.
While transplantation of the larynx may eventually be useful in post-laryngectomy reconstruction, three criteria must first be met before human transplants can be attempted: transplant viability must be high, immunosuppression must be safe and effective and functional recovery of the larynx must occur. To study these first two criteria, a total of 11 canine larynx transplants were performed: 3 autografts, 6 orthotopic allografts and 2 heterotopic allografts. The rationale and technical performance of these different transplant procedures are reviewed in detail. Orthotopic transplant recipients received cyclosporin A (CsA) while the heterotopic allograft recipients received RS-61443 and methylprednisolone in addition to CsA. Overall, 9 of 11 of the transplants remained viable. In contrast, all 3 autografted animals developed esophageal-cutaneous fistulas; 2 developed sepsis and were sacrificed on post-operative days (POD) 5 and 28, respectively. The third survived for 91 days and demonstrated a high degree of regeneration in the recurrent and superior laryngeal nerves of the transplant. Orthotopically transplanted dogs also had a high morbidity and perioperative mortality (5 of 6 animals). The single "long-term" survivor was treated with CsA alone, but developed complete transplant rejection on POD 33. The two heterotopic transplant recipients had no perioperative morbidity and the combination of CsA, RS-61443 and methylprednisolone given these latter animals was effective in the long-term prevention of rejection. One of these heterotopic recipients died of sepsis on POD 68 while the other remained alive and well on POD 168. Our present findings show that currently available microsurgical techniques allow experimental canine laryngeal transplantation to be done with significantly high transplant viability rates. (ABSTRACT TRUNCATED AT 250 WORDS)
Anthony
J P
JP
Department of Surgery, University of California at San Francisco 94143-0932, USA.
Allen
D B
DB
Trabulsy
P P
PP
Mahdavian
M
M
Mathes
S J
SJ
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D004285:Dogs; D004359:Drug Therapy, Combination; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007830:Larynx / Q000473:pathology / Q000637:transplantation*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D008866:Microsurgery; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects; D012009:Recurrent Laryngeal Nerve / Q000473:pathology / Q000637:transplantation; D016042:Transplantation, Heterotopic / Q000473:pathology; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D008775:Methylprednisolone