ArticleSurgery2015
Combined intraoperative administration of a histone deacetylase inhibitor and a neurokinin-1 receptor antagonist synergistically reduces intra-abdominal adhesion formation in a rat model.
Article in Surgery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Effect of Neurokinin-1 Receptor Antagonists on Experimental Postoperative Adhesion: A Systematic Review and Meta-Analysis with Trial Sequential Analysis of Preclinical Studies.Medicina (Kaunas, Lithuania) · 2025Pooled it
- Effects of valproic acid on wound healing of the abdominal wall musculoaponeurotic layer: an experimental study in rats.Revista do Colegio Brasileiro de Cirurgioes · 2024Article
- Connexin43 in Post-Surgical Peritoneal Adhesion Formation.Life (Basel, Switzerland) · 2022Article
- Valproic acid and bladder healing: an experimental study in rats.Revista do Colegio Brasileiro de Cirurgioes · 2022Article
- The effects of valproic acid on skin healing: experimental study in rats.Acta cirurgica brasileira · 2022Article
- Baseline performance of the ischaemic button model for induction of adhesions in laboratory rats.Laboratory animals · 2019Article
- Creation of Abdominal Adhesions in Mice.Journal of visualized experiments : JoVE · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIntra-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.
methodsRats underwent laparotomy with creation of peritoneal ischemic buttons to induce adhesions. A single dose of VPA (25 mg/kg), NK-1RA (50 mg/kg), a combination of both, or 0.9% saline was lavaged intraperitoneally just before wound closure. On postoperative day 7, adhesions were quantified. To investigate early mechanisms of adhesiogenesis, adhesions were created as described and adhesive button tissue was harvested at 30 minutes and 3 hours postoperatively and fibrinogen and vascular endothelial growth factor (VEGF) protein levels, both indices of peritoneal extravasations, were determined by Western blot analysis. Peritoneal fluid was collected in similar experiments at 30 minutes, and 3 and 6 hours to measure fibrinolytic activity, an index of the ability of the peritoneum to degrade fibrinous adhesions.
resultsThe coadministration of VPA plus NK-1RA reduces adhesions by 72.6% relative to saline (P < .001); this reduction was greater than either compound alone (P < .001). Peritoneal fibrinolytic activity was significantly increased at 3 and 6 hours postoperatively in animals administered the combination therapy versus saline (P = .01). VPA plus NK-1RA significantly decreased fibrinogen and VEGF protein levels at 3 and 6 hours compared with saline controls.
conclusionThese results suggest that a combined pharmacologic approach targeting multiple adhesiogenic pathways provides optimal adhesion prevention.
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