Shadya Betancourt-Vicencio, Manuel Rodrigo Prieto-Aldape, Andrea Socorro Alvarez-Villaseñor, Clotilde Fuentes-Orozco, Ana Olivia Cortes-Flores, Guadalupe Castillo-Cardiel, José Antonio Sánchez-Martínez, Emilio Alberto Reyes-Elizalde, Paola Guadalupe González-Hernández, José Gerardo Zamora-Inzunza, Victoria Amaranta Romero-Arredondo, José Francisco Barbosa-Camacho, Irma Valeria Brancaccio-Pérez, Bertha Georgina Guzmán-Ramírez, Alejandro González-Ojeda
{"title":"Effects of Oral Pirfenidone on Colon Anastomosis Healing and Adhesion Formation in Rats.","authors":"Shadya Betancourt-Vicencio, Manuel Rodrigo Prieto-Aldape, Andrea Socorro Alvarez-Villaseñor, Clotilde Fuentes-Orozco, Ana Olivia Cortes-Flores, Guadalupe Castillo-Cardiel, José Antonio Sánchez-Martínez, Emilio Alberto Reyes-Elizalde, Paola Guadalupe González-Hernández, José Gerardo Zamora-Inzunza, Victoria Amaranta Romero-Arredondo, José Francisco Barbosa-Camacho, Irma Valeria Brancaccio-Pérez, Bertha Georgina Guzmán-Ramírez, Alejandro González-Ojeda","doi":"10.1159/000523711","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, insulin-like growth factor type 1, synthetic metalloproteinases inhibitors, and hyperbaric oxygen therapy have produced promising results in low-risk models of anastomosis dehiscence. However, in high-risk models, only hyperbaric oxygen therapy has been shown to be useful. Pirfenidone (PFD), a commonly used antifibrosing drug, has not been shown to be effective for this purpose. Our objective was to evaluate the effects of PFD on anastomosis healing and adhesion genesis in a low-risk rat model of dehiscence of colonic anastomosis.</p><p><strong>Methods: </strong>An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis.</p><p><strong>Results: </strong>There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04).</p><p><strong>Conclusions: </strong>Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases.</p>","PeriodicalId":12222,"journal":{"name":"European Surgical Research","volume":"63 4","pages":"241-248"},"PeriodicalIF":1.7000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Surgical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000523711","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"SURGERY","Score":null,"Total":0}
引用次数: 2
Abstract
Introduction: Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, insulin-like growth factor type 1, synthetic metalloproteinases inhibitors, and hyperbaric oxygen therapy have produced promising results in low-risk models of anastomosis dehiscence. However, in high-risk models, only hyperbaric oxygen therapy has been shown to be useful. Pirfenidone (PFD), a commonly used antifibrosing drug, has not been shown to be effective for this purpose. Our objective was to evaluate the effects of PFD on anastomosis healing and adhesion genesis in a low-risk rat model of dehiscence of colonic anastomosis.
Methods: An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis.
Results: There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04).
Conclusions: Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases.
期刊介绍:
''European Surgical Research'' features original clinical and experimental papers, condensed reviews of new knowledge relevant to surgical research, and short technical notes serving the information needs of investigators in various fields of operative medicine. Coverage includes surgery, surgical pathophysiology, drug usage, and new surgical techniques. Special consideration is given to information on the use of animal models, physiological and biological methods as well as biophysical measuring and recording systems. The journal is of particular value for workers interested in pathophysiologic concepts, new techniques and in how these can be introduced into clinical work or applied when critical decisions are made concerning the use of new procedures or drugs.