Combined intraoperative administration of a histone deacetylase inhibitor and a neurokinin-1 receptor antagonist synergistically reduces intra-abdominal adhesion formation in a rat model.

Background: Intra-abdominal adhesions are the most frequent postoperative complication after abdominopelvic surgery. Our laboratory has previously shown that an intraoperative peritoneal lavage containing either the histone deacetylase inhibitor valproic acid (VPA) or a neurokinin-1 receptor antagonist (NK-1RA) reduced adhesions by approximately 50% in a rat model. The objective of this study was to determine whether the combination of these 2 drugs was more effective in reducing adhesions than either alone.

Histone deacetylase inhibitors decrease intra-abdominal adhesions with one intraoperative dose by reducing peritoneal fibrin deposition pathways.

Background: We previously demonstrated that postoperative peritoneal injury and inflammation contribute to adhesiogenesis. Recent evidence suggests that in addition to their role of interfering with the acetylation status of nuclear histone proteins, histone deacetylase inhibitors (HDACIs) including valproic acid (VPA) can target nonhistone proteins to resolve inflammation and modulate immune cells. We hypothesized that HDACIs could reduce adhesions.