Prevention of Postoperative Adhesion Formation Using Noninvasive Technology [38F

Abstract

INTRODUCTION: Postoperative adhesions occur following laparoscopic and open procedures, cause pain, infertility, bowel obstruction and other complications. Surgically-induced tissue injury causes inflammation and hypoxia resulting in alterations in cytochrome c oxidase (COX) activity, mitochondrial membrane potential (ΔΨm) hyperpolarization and reactive oxygen species (ROS) production. ROS initiate a cascade causing the irreversible transformation of fibroblasts to adhesion phenotype in injured peritoneum. Infrared light (IRL) can modulate COX activity through the following mechanism: IRL → COX activity↓ → ΔΨm↓ → ROS↓ → TGF-β1↓→ prevention of adhesion phenotype, making adhesion-free surgery possible. METHODS: Mitochondrial respiration, ROS, and ΔΨm were analyzed. Adhesion markers were measured by ELISA. Electrocautery and cytobrush were used to traumatize peritoneal tissue in Sprague-Dawley rats. Tissues, evaluated and harvested on day 7, were cryosectioned, hematoxylin/eosin stained, and immunofluorescence analyzed with confocal microscopy. IRL was generated by light emitting diodes. RESULTS: COX activity increases in injured peritoneum. IRL significantly decreased COX activity, whole cell respiration, ΔΨm, and ROS production. Hypoxia, ischemia/reperfusion and hyperoxia increased ROS, ΔΨmand TGFβ1 in macrophages, neutrophils and fibroblasts and transformed fibroblasts to adhesion phenotype. IRL robustly decreased ROS, ΔΨmand TGF-β1 and abrogated conversion to adhesion phenotype in vitro. Rats treated with IRL following adhesion surgery had lower numbers and severity of adhesions on gross examination, less fibrosis on histology and less adhesion marker expression on immunofluorescence compared to untreated controls. CONCLUSION: IRL may be used to non-invasively modulate COX activity, decrease ROS and decrease the conversion of fibroblasts to adhesion phenotype limiting postoperative adhesions.