Plastic Surgery Research Council
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PSRC 60th Annual Meeting
Program and Abstracts

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Changes in Skin Vascularity in a Murine Model for Post-Mastectomy Radiation
Jose J. Rodriguez, MD, Theodore A. Kung, MD, Yekaterina Polyatskaya, MD, Noah S. Nelson, BS, Yao Wang, MD, Sagar S. Deshpande, BS, Alexander R. Zheutlin, BS, Alexis Donneys, MD, Steven R. Buchman, MD, Adeyiza O. Momoh, MD.
University of Michigan, Ann Arbor, MI.

PURPOSE: Post-mastectomy radiation causes persistent injury to the breast microvasculature and therefore many surgeons recommend a delay between the completion of radiotherapy and autologous breast reconstruction. Although the prevailing assumption is that a longer delay period is beneficial to allow for some recovery of blood supply within irradiated tissues, there is little data demonstrating an optimal time for reconstruction. This study utilizes a murine model to examine the effects of radiation on skin vascularity in order to help determine when radiation-induced effects on the microvasculature begin to stabilize. We posit that there will be a transient hyper-vascularity associated with the inflammatory effects of XRT on vessel number and separation in skin, but that the pathological effects will moderate and plateau over a time.
METHODS: Isogenic Lewis rats were divided into two groups: Radiation (XRT, n=21) and Control (Control, n=19). Each XRT rat received a calculated human dose-equivalent of the standard 56 Gy of radiation (5 fractions of 5.6 Gy per fraction) to the left groin, whereas Control rats received no radiation. Animals were then sacrificed at 4 weeks, 8 weeks, 12 weeks, and 16 weeks after completion of the radiation protocol. The vasculature was injected with radiopaque compound (Microfil MV-122) and the left groin skin was harvested for analysis by micro-computed tomography (µCT). Analysis of the microvasculature was performed using quantitative radiomorphometrics to measure vessel number and vessel separation within the skin specimens.
RESULTS: An initial augmentation in vascularity was observed in the XRT group at 4 weeks following radiation compared to the Control group (Figure 1). However, vessel number was decreased at 12 weeks in the XRT rats compared to Control rats and remained relatively stable at 16 weeks. Furthermore, vessel separation in the XRT group was higher than in the Control group at 12 weeks and this did not significantly change at 16 weeks. Therefore, skin specimens from the XRT animals demonstrated reduced vascularity 12 weeks after radiation and this effect was steady at 16 weeks.
CONCLUSIONS: In a murine model for post-mastectomy radiation, a period of augmented vascularity is seen after radiation injury to the skin followed by decreased vascularity which demonstrates stabilization at approximately 12 weeks. The initial increase in vascularity is thought to be an inflammatory and pathological response, which subsequently subsides. This study affirms our hypothesis of a truncated stabilization time frame for the changes in vessel number and separation secondary to XRT . This data can be used to potentially lessen the time between post-mastectomy radiation and reconstruction currently employed in practice. This model can also be used to study potential interventions directed at improving skin flap vascularity prior to translation to human subjects.
Figure 1. Microvascular stereovascular parameters, Vessel Number.


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