Doxycycline administration improves fascial interface in hernia repair.

BACKGROUND: Despite improvements in ventral hernia repair techniques, their recurrence rates are unacceptably high. Increased levels of matrix metalloproteinases (MMPs) and reduced collagen-1 to -3 ratios are implicated in incisional hernia formation. We have recently shown doxycycline treatment for 4 wk after hernia repair reduced MMP levels, significantly increased collagen-1 to -3 ratios, and increased tensile strength of repaired interface fascia. However, this increase was not statistically significant. In this study, we extended treatment duration to determine whether this would impact the tensile strength of the repaired interface fascia. MATERIALS AND METHODS: Thirty-two male Sprague-Dawley rats underwent incision hernia creation and subsequent repair with polypropylene mesh. The animals received either saline (n = 16) or doxycycline (n = 16) beginning from 1 day before hernia repair until the end of survival time of 6 wk (n = 16) or 12 wk (n = 16). Tissue samples were investigated for MMPs and collagen subtypes using Western blot procedures, and tensiometric analysis was performed. RESULTS: At both 6 and 12 wk after hernia repair, the tensiometric strength of doxycycline-treated mesh to fascia interface (MFI) tissue showed a statistically significant increase when compared with untreated control MFI. In both groups, collagen-1, -2, and -3 ratios were remarkably increased in doxycycline-treated MFI. At 6 wk, the doxycycline-treated MFI group showed a significant decrease in MMP-2, an increase in MMP-3, and no change in MMP-9. At 12 wk, MMP-9 showed a remarkable reduction, whereas MMP-2 and -3 protein levels increased in the doxycycline-treated MFI group. CONCLUSIONS: Doxycycline administration results in significantly improved strength of repaired fascial interface tissue along with a remarkable increase in collagen-1, -2, and -3 ratios.

Biomaterial-dependent MMP-2 expression in fibroblasts from patients with recurrent incisional hernias.

With regard to the pathogenesis of recurrent incisional hernia, an impaired connective tissue quality leading to an aberrant scarring process has been proposed. For the matrix metalloproteinase (MMP-2) a pathogenetic involvement in direct inguinal hernia development is reported. With mesh implantation as the gold standard treatment for incisional hernias, the aim of the present study was to investigate the MMP-2 expression in patients with recurrent incisional hernias with and without mesh-materials. In primary fibroblast cultures obtained from skin scars in patients with and without recurrent incisional hernias, MMP-2 synthesis and gene expression were investigated. Furthermore, MMP-2 synthesis and gene expression of fibroblasts were compared after incubation with two different mesh materials: polypropylene and absorbable polyglactin filaments. MMP-2 enzyme activity was determined by semiquantitative zymography and mRNA synthesis by quantitative RT-PCR. Both MMP-2 enzyme activity and mRNA expression were similar in hernia and control fibroblasts in vitro. In control fibroblasts mesh incubation did not significantly affect MMP-2 expression, whereas polypropylene mesh contact of fibroblasts from patients with recurrent incisional hernias led to a major decrease of MMP-2 activity and of mRNA expression. In the absence of biomaterials fibroblasts from recurrent incisional hernia, patients have no alterations of their MMP-2 synthesis compared to control fibroblasts, whereas a specific response was found after biomaterial contact hereby indicating differences in fibroblast phenotype.

Gastroschisis increases small bowel nitric oxide synthase activity.

In gastroschisis, the eviscerated fetal bowel frequently is damaged and this results in hypoperistalsis and malabsorption. The mechanistic link that ties gastroschisis-induced intestinal damage to dysfunction may be nitric oxide (NO) and the enzyme responsible for producing it, NO synthase. Using a fetal rabbit model, the authors investigated the hypothesis that the hypoperistalsis and malabsorption associated with gastroschisis may be attributable to abnormal small bowel NO synthase activity. Using the 3H-arginine-to-3H-citrulline conversion assay, they measured NO synthase activity in the small bowel of full-term fetal rabbits with and without gastroschisis. The mean total small bowel NO synthase activity of fetal rabbits with gastroschisis was 2.5 times greater than that of control littermates without gastroschisis (n = 6; 5,726 +/- 834 v 2,208 +/- 537 mean pmol/mg protein/min; P = .004). This increased NO synthase activity also was studied by measuring the individual isoforms of NO synthase, and the site of increased NO synthase activity was localized to the small bowel epithelium and neurons. After detecting and localizing the gastroschisis-induced increase in NO synthase activity, the authors explored the mechanism of this increase using NADPH-diaphorase staining. With this histological staining technique, no quantitative increase was found in the small bowel NO synthase of the rabbits with gastroschisis. This suggests that the increased NO synthase activity found in these rabbits is the result of accelerated enzyme kinetics. These findings suggest that the increased NO synthase activity caused by gastroschisis may contribute to the common clinical sequelae of malabsorption and intestinal dysmotility.

Factores biológicos implicados en la génesis / Biological factors involved in the genesis of incisional hernia

En el contexto de la patología quirúrgica de la pared abdominal, la eventración o hernia incisional sigue siendo una de las afecciones de mayor prevalencia. Su incidencia no ha disminuido en los últimos años a pesar de la mejora en los materiales de sutura y también en las técnicas de cierre. Existen factores de índole general que pueden interferir en el proceso cicatricial de las laparotomías, pero hay factores de tipo biológico dependientes del propio individuo que pueden explicar en gran parte la inalterable incidencia de esta afección. Así, los diferentes tipos de colágenos, determinadas enzimas, como las metaloproteinasas, y ciertos hábitos, como el tabaquismo, han sido implicados en la aparición de esta afección. Probablemente sea necesario en casos de riesgo y cicatrización comprometida realizar los cierres laparotómicos con algún material protésico de apoyo, especialmente en las laparotomías medias (AU)

In the context of a surgically treated abdominal wall pathology, eventration of the wall, or incisional hernia, is one of the most prevalent complications. Despite numerous improvements over the years in suture materials and closure techniques, the incidence of incisional hernia has not diminished. Several general factors can influence the wound healing process after a laparotomy, but there are also biological factors that depend on the individual patient that can to a great extent explain the un-changing incidence of this pathology. Thus, different types of collagen, certain enzymes such as metalloproteinases and factors such as smoking have been attributed a role in the appearance of incisional hernia. These features suggest the need for a biomaterial to strengthen laparotomy closures, especially midline closures, in high-risk patients and/or in those where wound healing is compromised (AU)