Cryosurgery of normal and tumor tissue in the dorsal skin flap chamber: Part II - Injury response

It has been hypothesized that vascular injury may be an important mechanism of cryosurgical destruction in addition to direct cellular destruction. In this study, we report correlation of tissue and vascular injury after cryo surgery to the temperature history during cryosurgery in an in vivo microva scular preparation. The dorsal skin flap chamber implanted in the Copenhage n rat, was chosen as the cryosurgical model. Cryosurgery was performed in t he chamber on either normal skin or tumor tissue propagated from an AT-1 Du nning rat prostate tumor, as described in a companion paper (Hoffmann and B ischof 2001). The vasculature was then viewed at 3 and 7 days after cryoinj ury under brightfield and FITC-labeled dextran contrast enhancement to asse ss the vascular injury. The results showed that there was complete destruct ion of the vasculature in the center of the lesion and a gradual return to normal patency moving radially outward. Histologic examination showed a ban d of inflammation near the edge of a large necrotic region at both 3 and 7 days after cryosurgery. The area of vascular injury observed with FITC-labe led dextran quantitatively corresponded to the area of necrosis observed in histologic section, and the size of the lesion fur tumor and normal tissue was similar at 3 days post cryosurgery. At 7 days after cryosurgery, the l esion was smaller for both tissues, with the normal tissue lesion being muc h smaller than the tumor tissue lesion. A comparison of experimental injury data to the thermal model validated in a companion paper (Hoffmann and Bis chof, 2001) suggested that the minimum temperature required for causing nec rosis was -15.6 +/- 4.3 degreesC in tumor tissue and -19.0 +/- 4.4 degreesC in normal tissue. The other thermal parameters manifested at the edge of t he lesion included a cooling rate of -28 degreesC/min, 0 hold time, and a s imilar to9 degreesC/min thawing rate. The conditions at the edge of the les ion are much less severe than the thermal conditions required for direct ce llular destruction of AT-1 cells and tissues in vitro. These results are co nsistent with the hypothesis that vascular-mediated injury is responsible f or the majority of injury at the edge of the frozen region in microvascular perfused tissue.