Rat laryngeal transplant model: technical advancements and a redefined rejection grading system.

Abstract

The rat laryngeal transplant model, introduced in 1992, laid the basic science foundation that contributed to the first successful human larynx transplant in 1998. Over 1,500 rat transplants later, numerous modifications have improved the model, increasing the initially reported evaluability rate of 50% to almost 100%. The observed histologic rejection process has been altered, as well. We report the technique modifications, as well as the results of a new study using nonimmunosuppressed, allogenic transplantations, in order to define a new rejection grading system. Using the updated model, we performed 50 transplantations between LBN(f1) donor rats and Lewis recipients. Larynges from 8 groups of 5 to 10 animals were harvested at intervals between 1 and 20 days after transplantation. The larynges were examined grossly and microscopically in a blinded manner for evidence of rejection. A multivariable linear regression model was used to define a new rejection grading scale. All 50 animals survived their assigned posttransplantation period. No animals exhibited vascular thromboses, for an evaluability rate of 100%. Histologic criteria in 7 categories and gross criteria in 5 categories demonstrated increased rejection proportional to the amount of time after transplantation. The equation [Group = -2.209 + 0.465 x (Size) + 0.901 x (VA Flow) + 0.613 x (Muscle) + 1.040 x (Thyroid)] reproducibly grades rejection on the basis of gross and histologic findings. New modifications to the rat laryngeal transplant model have conferred greatly improved animal survival rates and anastomotic patency rates. Additionally, the observed rates of rejection have been reduced in comparison to those of initial studies. This updated rejection staging system will be used to compare immunosuppressive regimens in future rat laryngeal transplant studies.