Increased Signs of Acute Rejection with Ischemic Time in a Rat Musculocutaneous Allotransplant Model

Background: Composite tissue allotransplantation (CTA) may restore a variety of tissue defects, but carries the potential risks of graft failure and/or immunosuppression-related complications. Ischemia-reperfusion injury has been documented in CTA is known to contribute to acute rejection of solid organ grafts. This study describes the influence of subcritical ischemic time (ie, ischemia sufficient to generate reversible cell damage) on signs of rejection of musculocutaneous allograft components of subcritical ischemic time, namely, ischemia sufficient to generate reversible cell injury. Although skin is considered the most antigenic component of a composite allograft and is currently used for rejection surveillance, muscle and adipose are more susceptible to ischemia-related injury.

Methods: Vascularized epigastric flaps were transplanted from WKY to Fisher 344 rats after 1 or 3 hours of ischemia. Biopsies taken on postoperative day 6 were graded for signs of acute rejection according to criteria modified from previously published grading systems for CTA rejection.

Results: Skin and muscle exposed to 3 hours of ischemia showed significantly higher rejection scores than after 1 hour of ischemia, as evidenced by a more aggressive diffuse lymphocytic infiltration with disruption of tissue architecture. The rejection score in skin with 3-hour ischemia was 5.0 +/- 0.1 versus 3.7 +/- 0.2 with 1-hour (Mann-Whitney U test; P < .05). The rejection score in muscle exposed to 3-hour ischemia was 3.6 +/- 0.3 versus 2.5 +/- 0.1 with 1-hour (P < .05).

Conclusions: Muscle and skin demonstrated increased acute rejection of allotransplants with increased subcritical ischemic time. This study supports the use of aggressive methods to reduce subcritical ischemic injury during allotransplantation of composite tissue and inclusion of muscle in postoperative biopsies in this early investigational period of CTA.