Pharmacological Regulation of the Inflammatory Response under Mesh Implant Prosthetics in the Treatment of Patients with External Abdominal Hernias

Introduction. Seromas and hematomas of the implantation area are among the most common complications in prosthetic repair of a hernia defect with a mesh implant. The adequate tissue inflammation response to prosthesis implantation is achieved by the local protective role of pro-inflammatory cytokines. With suppression of the body's immune system combined with existing comorbidities, mesh implants result in even greater suppression of the immune system, which is manifested by an inadequate inflammatory response, both local and systemic, leading to the development of complications.Previously, the authors studied the effect of pyrimidine preparation "Xymedon" (INN - hydroxyethyldimethyldihydropyrimidine) on the systemic inflammatory process after prosthetic repair of anterior abdominal wall hernias. Based on the results of the interim study, it was hypothised: Regulation of the inflammation response to prosthesis implantation in hernioplasty manifested by changes in cytokine concentration in the blood can reduce postoperative complications. The aim of the study was to reduce the number of postoperative complications in prosthetic hernioplasty by regulating inflammatory reactions that occur after mesh implants.Materials and methods. Experimental part of the study. The experiment involved 66 rats, both sexes, pure line, which were implanted with mesh prostheses. Animals in group I (n=33) the control one - received 1 ml of 0,9% sodium chloride solution, i.e. received no specific treatment. Animals in group II (n=33) - the main one - received "Ximedon" 21 mg/day as pharmacological support. Blood sampling to determine inflammation markers was performed on the 5th day after the intervention. Animals were withdrawn from the experiment and the implantation site was taken for histological and histomorphometric investigations on the 5th day of the study. The study was carried out in the SPF vivarium at the laboratory of the Center for Genetic Collections of Laboratory Animals, Lobachevsky State University of Nizhny Novgorod. The study consisted of 4 series of experiments (2018-2021). Clinical part of the study. Prospectively (2018 - February 2022), we analyzed clinical outcomes of 101 patients with prosthetic repair (by Liechtenstein, TAPP, eTAR, "sublay") of an aponeurosis hernia defect of the anterior abdominal wall who received treatment in the City Clinical Hospital №7 named after E.L. Berezow. Patients of the "control" group (n=33) received only conventional treatment; patients of the "Ximedon" group (n=68) received 0.5 mg of ximedon 3 times a day for 10 days orally from the first day after the operation. Blood sampling was carried out on the 5th day after surgery. The data obtained were processed and structured using Microsoft Excel 2019 (64 bit), and statistical values were calculated in StatSoft Statistica 12,5 (64 bit).Results. Xymedon has a significant effect on the increase in the area of ​​the vessels of the implantation area in the experiment. Its use is associated with a lower level of C-reactive protein and blood IL-6 on day 5 in the experimental group compared to the control group. In the clinical study ximedon has a significant effect on the cytokine concentration in the blood: C-reactive protein, TNF-a, interleukins 6, 8 and 10. In the experimental study the dynamic of C-reactive protein, blood interleukins 6 and 10 does not significantly differ from the clinical one. In the clinical study, xymedon intake was associated with fewer postoperative complications. Conclusion. The studies performed allow us to consider "ximedon" as a means of pharmacological support for prosthetic repair in external abdominal hernias due to a significant reduction in postoperative complications provided by the ability to regulate inflammation reactions and stimulate reparative regeneration.