Ischemia‐reperfusion injury in chronic pressure ulcer formation: A skin model in the rat

TLDR

Existing chronic pressure ulcer models mainly examine ischemic injury with single constant pressure applications. The study aimed to create and characterize a reproducible cyclic ischemia‑reperfusion skin injury model in un‑anesthetized rats using clinically relevant pressures and durations. Cyclic ischemia‑reperfusion was induced in a 9 cm² dorsal skin area of male rats by periodically compressing the skin to 50 mm Hg with an implanted metal plate and overlying magnet, varying cycle number, frequency, and duration to compare ischemia‑only versus ischemia‑reperfusion injury. Increasing the number, duration, and frequency of cycles produced greater tissue injury—necrosis, thicker wounds, leukocyte infiltration, lower transcutaneous oxygen tension, and altered wound blood flow—showing the model’s reproducibility and suitability for biomarker and therapeutic studies.

Abstract

Most animal models of chronic pressure ulcers were designed to study only the role of ischemic injury in wound formation, often using single applications of constant pressure. The purpose of this study was to develop and characterize a reproducible model of cyclic ischemia‐reperfusion injury in the skin of small un‐anesthetized animals using clinically relevant pressures and durations. Ischemia‐reperfusion injury was created in a 9 cm 2 region of dorsal skin in male rats by periodically compressing skin under a pressure of 50 mm Hg using an implanted metal plate and an overlying magnet. We varied the total number of ischemia‐reperfusion cycles, examined the effect of varying the frequency and duration of ischemic insult, and compared ischemia‐induced injury to ischemia‐reperfusion‐induced injury with this model. Tissue injury increased with an increasing number of total ischemia‐reperfusion cycles, duration of ischemia, and frequency of ischemia‐reperfusion cycles. This model generates reproducible ischemia‐reperfusion skin injury as characterized by tissue necrosis, wound thickness, leukocyte infiltration, transcutaneous oxygen tension, and wound blood flow. Using this model, the biological markers of ischemia‐reperfusion‐induced wound development can be studied and therapeutic interventions can be evaluated in a cost‐effective manner.