Betancourt-Vicencio Shadya, Prieto-Aldape Manuel Rodrigo, Alvarez-Villaseñor Andrea Socorro, Fuentes-Orozco Clotilde, Cortes-Flores Ana Olivia, Castillo-Cardiel Guadalupe, Sánchez-Martínez José Antonio, Reyes-Elizalde Emilio Alberto, González-Hernández Paola Guadalupe, Zamora-Inzunza José Gerardo, Romero-Arredondo Victoria Amaranta, Barbosa-Camacho José Francisco, Brancaccio-Pérez Irma Valeria, Guzmán-Ramírez Bertha Georgina, González-Ojeda Alejandro
Biomedical Research Unit 02, Western National Medical Center, Social Security Mexican Institute, Guadalajara, Mexico.
Auxiliary Medical Coordination of Health Research, Mexican Institute of Social Security, Baja California Sur, Mexico.
Eur Surg Res. 2022;63(4):241-248. doi: 10.1159/000523711. Epub 2022 Feb 23.
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.
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.
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).
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.
许多实验研究已对多种药物或治疗方法进行了检验，以促进肠道吻合口的愈合。合成前列环素类似物、免疫抑制剂、促红细胞生成素、生长激素、胰岛素样生长因子1、合成金属蛋白酶抑制剂以及高压氧疗法在吻合口裂开的低风险模型中已产生了有前景的结果。然而，在高风险模型中，仅高压氧疗法已被证明是有用的。吡非尼酮（PFD），一种常用的抗纤维化药物，尚未被证明在此目的上有效。我们的目的是评估PFD对结肠吻合口裂开低风险大鼠模型中吻合口愈合及粘连形成的影响。
对40只健康的Wistar大鼠进行了一项实验研究，将其随机分为对照组或PFD实验组（每组20只大鼠）。所有动物均采用相同技术在腹膜返折上方3 cm处进行结肠吻合。通过测量破裂压力来研究机械阻力。使用常用染色技术对粘连进行宏观和组织学评估。动物在术后12 h接受首剂PFD，剂量为500 mg/kg，每天一次（SID），连续5天。在第6天，对动物再次进行手术，以原位测量破裂压力并宏观上对粘连进行分类，然后切除吻合的结肠进行组织学分析。
两组均无死亡、并发症或吻合口裂开。对照组和PFD组的平均破裂压力分别为120.8±11 mmHg和135.5±12.4（p<0.001）。PFD组的粘连密度较低且炎症细胞浸润较少（分别为p<0.02和0.002）。PFD组的胶原蛋白含量略高（p = 0.04）。
我们的结果揭示了PFD在这个低风险结肠吻合模型中的有利作用；例如，PFD组的破裂压力更高，宏观粘连较软，炎症浸润较少且胶原蛋白含量高于对照组。显示PFD治疗与轻微粘连更好愈合相关的结果似乎自相矛盾，因为该药物的治疗适应证是针对治疗纤维化疾病的。
