Effects of bromopride on expression of metalloproteinases and interleukins in left colonic anastomoses: an experimental study

Anastomotic dehiscence is the most severe complication of colorectal surgery. Metalloproteinases (MMPs) and interleukins (ILs) can be used to analyze the healing process of anastomosis. To evaluate the effects of bromopride on MMP and cytokine gene expression in left colonic anastomoses in rats with or without induced abdominal sepsis, 80 rats were divided into two groups for euthanasia on the third or seventh postoperative day (POD). They were then divided into subgroups of 20 rats for sepsis induction or not, and then into subgroups of 10 rats for administration of bromopride or saline. Left colonic anastomosis was performed and abdominal sepsis was induced by cecal ligation and puncture. A colonic segment containing the anastomosis was removed for analysis of gene expression of MMP-1α, MMP-8, MMP-13, IL-β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). On the third POD, bromopride was associated with increased MMP-1α, MMP-13, IL-6, IFN-γ, and IL-10 gene expression. On the seventh POD, all MMP transcripts became negatively modulated and all IL transcripts became positively modulated. In the presence of sepsis, bromopride administration increased MMP-8 and IFN-γ gene expression and decreased MMP-1, TNF-α, IL-6, and IL-10 gene expression on the third POD. On the seventh POD, we observed increased expression of MMP-13 and all cytokines, except for TNF-α. In conclusion, bromopride interferes with MMP and IL gene expression during anastomotic healing. Further studies are needed to correlate these changes with the healing process.

Histological study of the left colon of rats after extra-mucosal seromyotomy (continent valves): evaluation of colonic emptying / Estudo histológico do cólon esquerdo de ratos após a confecção de seromiotomias extra-mucosas (válvulas continentes): avaliação do grau de esvaziamento do conteúdo colônico

PURPOSE: To elaborate an animal model with the objective of studying the continence of the biological valves surgically performed in the left colon of rats. METHODS: Thirty four rats were operated on and divided into three groups (G). G1 (sham) animals which underwent laparotomy only; G2 (perineal amputation without valves): animals which underwent amputation of the anal sphincter complex combined with a perineal colostomy; G3 (abdominoperineal amputation combined with valves): animals which underwent abdominoperineal amputation combined with three, equidistant and circumferential (360(0)), extra-mucosal seromyotomies, of the descending colon, which were sutured to create biological valves combined with perineal colostomy. Animals were euthanized in the late postoperative period and surgical valves were saved for histopathological study. RESULTS: Surgical procedure provoked intestinal dilation, as well as segmented chambers along the descending colon. Retained fecalomas between the valves and proximal to them were also noted. Six rats died of intestinal obstruction due to fecal impaction at the surgical site. The sequence of events was: stasis, obstruction, distention, perforation, peritonitis and death. Histopathology showed inflammation due to foreign body type reaction around the sutured colon causing partial concentric stenosis, capable of interfering normal mechanical activity of the distal colon. This process resulted in retardation of the intestinal transit. CONCLUSION: Extra-mucosal seromyotomies, with seromuscular suture, can be used as an operative procedure capable of causing retardation in the intestinal transit of rats.

OBJETIVO: Modelo de experimentação, com confecção de válvulas biológicas no cólon esquerdo de ratos com o objetivo de estudar o grau de continência dessas válvulas. MÉTODOS: Trinta e quatro ratos foram operados e distribuidos em três grupos: G1 (grupo simulado) submetido apenas à laparotomia, G2 (grupo amputado sem válvula) submetido à amputação do conjunto esfincteral mais colostomia perineal e G3 (grupo amputado com válvula) submetido à amputação do conjunto esfincteral, confecção de três seromiotomias extra-mucosas, eqüidistantes e circunferenciais (360(0) - válvulas biológicas), no colon descendente mais colostomia perineal. No pós-operatório tardio, os animais dos três grupos foram submetidos à eutanásia para coleta da peça cirúrgica e estudo histopatológico das válvulas. RESULTADOS: Os resultados mostraram que o procedimento culminou em dilatação intestinal, confirmada pela formação de verdadeiras câmaras de segmentação e pela presença de fecalomas retidos entre as válvulas e cranialmente a elas. Seis ratos morreram em decorrência de obstrução intestinal por impacção de fezes no local operado, na seqüência: obstrução, estase, distensão, perfuração, peritonite e morte. As alterações histopatológicas confirmaram o processo inflamatório com reação do tipo corpo estranho, no perímetro do cólon suturado, proporcionando uma estenose parcial concêntrica, levando à alteração da atividade mecânica do cólon distal, resultando no retardo do trânsito intestinal. CONCLUSÃO: As seromiotomia extramucosas, com sutura seromuscular, podem ser utilizadas como técnica operatória para se obter retardo do trânsito intestinal em ratos.