Adenoviral-mediated gene expression of hepatocyte growth factor prevents postoperative peritoneal adhesion in a rat model

BACKGROUND: Mesothelial cell proliferation and migration play important roles in reducing formation of postoperative peritoneal adhesions. Hepatocyte growth factor (HGF) is a multifunctional cytokine that stimulates proliferation and migration of various cell types, including mesothelial cells. METHODS: We investigated the effect of adenovirus-mediated HGF gene expression on the proliferation and migration of mesothelial cells and evaluated its preventive effects on postoperative formation of peritoneal adhesions. Rat mesothelial cells were isolated and characterized by expression of cytokeratin and vimentin. RESULTS: Immunohistochemical staining showed that these cells expressed c-Met, the receptor for HGF. Adenoviral-mediated HGF gene transfer into mesothelial cells resulted in high expression of HGF and enhanced migration. To evaluate the preventive effects of adenoviral-mediated HGF gene transfer on the formation of postoperative peritoneal adhesion, we employed a rat model of cecum abrasion-induced adhesion formation in which 80% of the rats developed postoperative peritoneal adhesions. Local application of recombinant adenovirus carrying the HGF gene reduced adhesion formation in 16 of 20 control rats compared with 7 of 20 treated rats in this model. CONCLUSIONS: These results suggest that adenoviral-mediated HGF gene transfer may be a novel strategy for preventing postoperative peritoneal adhesions.     

Tropical application of halcinonide cream reduces the severity and incidence of intraperitoneal adhesions in a rat model

BACKGROUND: Systemic or intraperitoneal administration of corticosteroids has been reported to have conflicting effects on the prevention of peritoneal adhesions. Painting corticosteroid cream directly on the likely site of adhesion formation, owing to its high concentrations and persistent effects, may be a promising approach to prevent peritoneal adhesion formation. METHODS: Adhesions were induced by abrading of the cecum, followed by dropping of 95% ethanol. Sixty Wistar rats were randomly allocated to two control groups with no further treatment of the cecum and to two therapy groups treated with 0.1% halcinonide cream painted directly on the damaged surface of the cecum. After 3 and 7 days, adhesion scores, adhesion incidence, and intraperitoneal leukocytes were evaluated. RESULTS: On both postoperative days 3 and 7, halcinonide cream resulted in a significant decrease in mean adhesion scores (6.80 versus 0.67, 10.40 versus 1.26; P <0.001, P <0.001, respectively). The adhesion incidence was 43.3% for the therapy groups and 100% for controls (P <0.01). On day 3, the total numbers of intraperitoneal leukocytes were 120.73 +/- 24.01 millions for the therapy groups and 270.40 +/- 34.68 for controls (P <0.001). CONCLUSIONS: Painting halcinonide cream directly on the damaged surface of the cecum could effectively reduce the severity and incidence of adhesion, possibly by suppression of early inflammatory exudate and of late fibroblast invasion and proliferation.     

The influence of adhesion prophylactic substances and taurolidine/heparin on local recurrence and intraperitoneal tumor growth after laparoscopic-assisted bowel resection of colon carcinoma in a rat model

Backgroud: The goal of the study was to investigate the influence of adhesion prophylactic substances (Interceed/lntergel) as well as taurolidine/heparin on intraperitoneal tumor growth and the local recurrence rate after laparoscopic cecum resection in a rat tumor model. Methods: Sixty BDIX rats were randomized in three therapy groups and one control group. A laparoscopic-assisted cecum resection was performed via three-trocar method after intraperitoneal tumor cell application (10,000 cells) of a colon carcinoma cell line (DHD/K1/TRb) in all animals. According to the randomization, the cecum suture and a 1 × 1-cm peritoneal defect were either covered with Intergel/Interceed or 1 ml of 0.5% taurolidine 10 IU heparin. The control group underwent instillation of 1 ml 0.9% NaCl solution. After 4 weeks the animals were euthanized and intraperitoneal tumor growth, local recurrence rate, and the number of intraperitoneal adhesions were determined. Results: The local recurrence rate was not significantly affected by any of the substances. Nevertheless, taurolidine/heparin significantly reduced the total number and weight of intraperitoneal metastases. The formation of adhesions was not significantly influenced by adhesion prophylaxis substances or by taurolidine/heparin. Conclusions: Taurolidine/heparin led to a significant reduction of intraperitoneal tumor growth after intraperitoneal application, whereas local tumor recurrence was not significantly influenced. This might be due to the number of injected tumor cells in this cell suspension model. Interceed and Intergel did not reduce intraperitoneal tumor growth. Furthermore, adhesion formation was not reduced by any of the substances.     

Evaluation of breviscapine on prevention of experimentally induced abdominal adhesions in rats

Background

Adhesion formation, which results from mechanical peritoneal damage, tissue ischemia, or the presence of foreign materials, is a complicated process. The formation of adhesions is associated with inflammatory response and extracellular matrix deposition in response to injury. Although the pathophysiology of adhesion formation is widely understood, an absolute solution to this problem does not exist yet. As a main component of Erigeron breviscapus, breviscapine has exhibited the ability of anti-inflammatory and antifibrosis on many diseases. The purpose of this study was to investigate the effect of breviscapine on the development of postoperative intra-abdominal adhesions in Wistar rats.

Methods

Abdominal adhesions were induced by scraping the cecum in rats. Various dosages of breviscapine drugs were administered for 10 days after surgery. On the 11th day after surgery, the levels of interleukin (IL) 18, IL-6, tumor necrosis factor α in blood serum and transforming growth factor β₁ (TGF-β₁), connective tissue growth factor, tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1) in peritoneal fluid were determined by enzyme linked immunosorbent assay. The expression of Smad7 and TGF-β₁ in rat cecum tissue was evaluated by Western blot analysis. Grades of intestinal adhesion were ranked by macroscopic observation.

Results

The intraperitoneal administration of breviscapine is effective on the prevention of the formation of postoperative adhesions in rats. Breviscapine decreased the levels of IL-18, IL-6, and tumor necrosis factor-α in blood serum and TGF-β₁, connective tissue growth factor, PAI-1 in peritoneal fluid. But the levels of tPA and the ratio of tPA and PAI-1 in peritoneal fluid were increased. In addition, breviscapine significantly inhibited the expression of TGF-β₁ and increased the level of Smad7 in the rat cecum tissue.

Conclusions

These results suggested that intraperitoneal administration of breviscapine was effective in preventing intra-abdominal adhesion formation in rats. Breviscapine appears to have synergetic effects which could decrease fibrosis by inhibiting inflammation, upregulating peritoneal fibrinolytic activity and regulating the TGF and/or Smad signaling pathway. These data indicated a potential new therapeutic use of breviscapine on adhesion prevention.     

Preventing recurrent postoperative adhesions: an experimental study in rats

A peritoneal lavage model, cyclic intraperitoneal lavage (CIPL), and other adhesion preventing methods with and without fibrinolytic agents were compared to a control group without treatment in an animal study. The adhesion-preventing effect was evaluated at the site of a standardized peritoneal defect (free peritoneal grafting, P) and at the laparotomy wound (L) of 60 rats (12 escape) after surgical lysis of primary adhesions during relaparotomy In five test groups with different treatments and in a control group without treatment recurrent adhesions were investigated during relaparotomy according to an adhesion grading scale with increasing severity (O-III). In the control group only severe adhesions grade II and III were observed. The five test groups showed different distributions of grade 0-II adhesions: compared to the control group a significant difference of the preventing effect was seen after CIPL with 1.36% glucose solution (as used for peritoneal dialysis) and after CIPL with Ringer's solution at the sites P and L, after a one-time irrigation with Ringer's solution only at the peritoneal graft P. Fibrinolytic agents used in CIPL or as single dose application failed to show an improvement compared to the control group.     

Reduction of surgery-induced peritoneal adhesions by continuous release of streptokinase from a drug delivery system

Postoperative abdominal adhesions may lead to intestinal obstruction and infertility. The effect of continuous release of streptokinase to the peritoneal cavity on postoperative adhesions was examined under experimental conditions. Peritoneal adhesions were induced in rats and the animals were further treated by intraperitoneal administration of streptokinase solution, polyhydroxybutyrate-co-hydroxyvalerate (PHBV) membrane alone and streptokinase loaded PHBV membrane and compared to sham operated and untreated groups. Formation of adhesions was evaluated by quantitative macroscopic grading, histopathologically with light microscopy, on the following week. Streptokinase loaded PHBV prevented postoperative adhesion formation in 90% of the cases. PHBV membrane alone also reduced the severity of adhesions due to its anti-adhesive properties. Histopathological examination revealed limited foreign body reaction due to PHBV. Continuous streptokinase activity in the peritoneal cavity during early post-surgical period prevents postoperative adhesion.     

Reduction in postoperative adhesion formation and re-formation after an abdominal operation with the use of N, O - carboxymethyl chitosan

BACKGROUND: Postoperative adhesions have proven to be intractable complications after abdominal operations. This study assessed the efficacy of N, O - carboxymethyl chitosan (NOCC) to limit adhesion formation and re-formation in a rabbit abdominal surgery model. METHODS: In study 1 (adhesion formation), injuries to the large bowel, cecum, and abdominal sidewall were generated in rabbits. The rabbits (10/group) were randomly assigned to 1 of 5 treatment groups: Group A received no NOCC treatment; in group B, NOCC gel was applied directly to the injured site and NOCC solution was applied throughout the abdominal cavity; in group C, NOCC gel was applied near the injured site and NOCC solution was applied as above; in group D, NOCC gel was applied distant to the injury and NOCC solution was applied as above; in group E, a mixture of NOCC gel and solution was applied at the injured site. Adhesions were evaluated 14 days later. In study 2 (adhesion re-formation), adhesions were generated as above but were then lysed by careful dissection. After adhesiolysis, the rabbits (9/group) were treated with NOCC gel and solution at the site of adhesiolysis or left untreated. Adhesion re-formation was assessed 14 days later. In study 3 (mechanism of action), sterile tissue culture plates were coated with NOCC and adhesion of cultured, radiolabeled murine fibroblasts to the plates was assessed. RESULTS: In study 1, animals treated with NOCC gel and solution showed reduced adhesion formation (P<.01). NOCC gel was equally efficacious if applied on the site of injury or near the site of injury but less efficacious if applied at a site distant to the injury. In study 2, animals treated with NOCC gel and solution showed less adhesion re-formation compared with the untreated control animals (P<.01). In study 3, murine fibroblasts did not adhere to NOCC-coated tissue culture plates. CONCLUSIONS: NOCC gel and solution can reduce adhesion formation and re-formation in this rabbit model. The inability of fibroblasts to adhere to NOCC solution-coated surfaces suggests that NOCC may act as a biophysical barrier.     

Enteric bacteria and their antigens may stimulate postoperative peritoneal adhesion formation

BACKGROUND: Intraabdominal sepsis causes exuberant inflammation, which results in dense adhesions. Translocation of enteric bacteria and/or their antigens after laparotomy may therefore also affect peritoneal healing by promoting local release of proinflammatory cytokines. Our hypothesis was that targeted counter therapy could be beneficial if such contamination was to augment postoperative adhesion formation. METHODS: Two endotoxin-hyposensitive mouse strains (C3H/HeJ and C57BL/10ScCr) and their syngeneic counterparts (C3H/HeN and C57BL10/ScSn, respectively) underwent reproducible adhesion-inducing operation (AIO) (n=10/group) with sacrifice and blinded adhesion grading 14 days later. In addition, CD-1 mice were gavaged with fluorescein isothiocyanate labeled-lipopolysaccharide (FITC-LPS) prior to either AIO or sham laparotomy and had both peritoneal macrophages and circulating monocytes assessed by flow cytometry afterward. The cytokine-release response of resident peritoneal cells to LPS stimulation was assessed in vitro (murine peritoneal mast cell cultures) and in vivo (unoperated CD-1 mice administered LPS intraperitoneally [10 & 50 microg/mouse]). Finally, CD-1 mice (n=10/group) had AIO and received either bactericidal/permeability increasing protein (rBPI, 2 mg/mouse) or vehicle solution in the early postoperative period with assessment of adhesion formation 2 weeks later. RESULTS: Both HeJ and ScCr mice had less adhesions than their controls (P=.0015 and .0001, respectively, Mann Whitney U test). FITC-LPS uptake by peritoneal macrophages was striking after AIO. Intraperitoneal LPS provoked significant local vascular endothelial growth factor (VEGF) release as did the process of AIO. In vitro, LPS induced significant interleukin-(IL)-6 release from isolated mast cells. Intraperitoneal administration of rBPI to CD-1 mice early after AIO markedly attenuated subsequent adhesion formation (P=.0003). CONCLUSIONS: Peritoneal adhesion formation is exacerbated by peritoneal contamination due to translocation after laparotomy and may be attenuated by therapeutic antagonism.     

Reduction of intestinal adhesions by postoperative peritoneal irrigation with dialysis solution

In a canine experimental model in which intestinal adhesions were created by exposing the intestine to talc powder and autologous blood, the incidence of adhesion formation and the severity of adhesions were reduced tenfold when the abdominal cavity was irrigated with peritoneal dialysis solution three times daily for 4 days postoperatively. The mechanism of peritoneal dialysis solution in reducing the severity of adhesion appears to be related to the mechanical factors of washing out debris from the abdominal cavity, although it may also have a fibrinolytic effect. Long-term use of peritoneal dialysis solution may alter systemic fluid and electrolyte imbalance. Placing a small peritoneal dialysis catheter in the abdominal cavity at the conclusion of major abdominal operations and subsequent daily irrigation with peritoneal dialysis solution may be a helpful adjunct in reducing the incidence of postoperative adhesions.     

Prevention of intraperitoneal adhesions by intraperitoneal lavage and intraperitoneal 5-fluorouracil: experimental studies

Postoperative adhesions remain the leading cause of small bowel obstruction. Peritoneal adhesions were induced in 180 rats by scraping the cecum and burning the adjacent parietal peritoneum by electrocoagulation. The adhesions were scored 14 days later in a blinded manner. All four types of intraperitoneal instillations significantly reduced the extension and the severity of the adhesions, at both schedules, when compared to the control group. The use of 5-fluorouracil at 20 mg/kg in peritoneal dialysis solution during 5 days significantly decreased the global score (P = 0.04), the extension (P = 0.04), and the severity (P = 0.04) of adhesions when compared to the 5-day instillation of peritoneal dialysis alone. Lavage of the abdomen with peritoneal dialysis solution or hetastarch decreased the formation of adhesions. Instillation of 5-fluorouracil in a large volume of peritoneal dialysis solution could be novel and promising treatments for prevention of postoperative adhesions.     

Role of fibrinolysis in the formation of postoperative adhesions

It has been hypothesized that peritoneal hypofibrinolysis is of importance in the formation of postoperative adhesions, but results from experiments with fibrinolytic modulators are conflicting. We tested this hypothesis in a controlled prospective study in rabbits, comparing the effects of fibrinolytic inhibition (tranexamic acid) to fibrinolysis enhancement by local instillation of gel containing tissue-type plasminogen activator. Adhesion formation was measured after 1 week in a strictly standardized way and is presented as a percentage of an induced lesion that was covered by adhesions. Fibrinolytic inhibition significantly increased adhesion formation, both to the parietal peritoneum (34.2%+/- 3.2%) compared with untreated control (19.7%+/- 3.3%, p < 0.01) and to the bowel (76.3%+/- 5.8%) compared with untreated control (51.2%+/- 8.7%, p < 0.05). Control gel significantly increased adhesions to the parietal peritoneum (35.6%+/- 4.6%) versus untreated control (19.7%+/- 3.3%, p < 0.05), whereas gel containing tissue-type plasminogen activator significantly reduced the amount of adhesions to the parietal peritoneum (4.9%+/- 1.7%) compared with untreated control (19.7%+/- 3.3%, p < 0.01) and abolished adhesion formation to the injured bowel. The fibrinolytic system thus seems to be intimately involved in the early formation of intraabdominal adhesions.     

The effectiveness of systemic antibiotics in preventing postoperative, intraabdominal adhesions in an animal model.

OBJECTIVE: Postoperative intraabdominal adhesions can be prevented by antibiotic lavage. We assessed whether systemic antibiotics could prevent adhesion formation in a rat model. METHODS: Cecal abrasion was performed in the peritoneal cavities of 40 Wistar albino rats. Twenty rats were treated with a 5-day course of cefepim and metronidazole; the remaining animals were given saline injections. The animals were sacrificed 14 days after surgery. Adhesion severity scores and histopathologic findings were compared. RESULTS: The median adhesion severity score was 2 (0-3) in the antibiotic group and 2.5 (1-4) in the controls (P = 0.03). In tissue specimens from controls, the adhesions were marked by mature collagen bundles. In treated rats, the adhesions were immature, characterized by early inflammatory cells, less collagen formation, and no collagen bundles. CONCLUSIONS: Postoperative systemic antibiotics slow adhesion formation and reduce the severity of the adhesions.     

Experimental adhesion prophylaxis with recombinant tissue plasminogen activator.

The deposition of fibrin in the peritoneal cavity leads to fibrous adhesion formation. Recombinant tissue plasminogen activator (rtPA), delivered locally, was investigated as a method of preventing adhesion formation. Six standardised areas of peritoneal ischaemia were formed in each of 36 male Wistar rats randomised to three intraperitoneal treatments: (A) no treatment control; (B) carboxymethylcellulose gel; (C) rtPA-carboxymethylcellulose gel combination. At 1 week all animals underwent relaparotomy and the number of ischaemic sites with an adhesion counted by an independent observer. rtPA-treated animals formed fewer adhesions compared with gel alone or controls (median number of adhesions 1.5 versus 2.5 versus 5, P < 0.001, ANOVA). Intraperitoneal rtPA in a slow-release formulation is able to reduce adhesion formation significantly in an animal model and may prove to have clinical benefit.     

腺病毒介导的鞘氨醇激酶基因转移预防术后肠粘连

目的 探讨SPK1是否能修复损伤的间皮层,预防术后腹膜粘连的发生.方法 细胞划痕实验检测间皮细胞的迁移.[y-32P]ATP掺入法检测细胞SPK酶活性.用无菌干纱布及手术刀损伤大鼠回盲部和子宫角浆膜层,建立了盲肠擦伤和子宫角刮伤诱发肠粘连的大鼠实验模型.分别将Ad-GFP和Ad-SPK1涂抹于模型大鼠腹腔浆膜层,14d后处死大鼠,评价粘连形成情况.结果 腺病毒能有效介导GFP和SPK1基因在腹腔浆膜层细胞中表达.腺病毒介导的SPK1基因转移能促进间皮细胞增殖和迁移.粘连评分结果 ,大鼠回盲部粘连模型:对照组和Ad-SPK1组的粘连中值分别为2.6和O.975,大鼠子宫角粘连模型:对照组和Ad-SPK1组的粘连中值分别为1.275和0.275,两种模型中Ad-SPK1组的粘连平均分值明显低于对照组(P＜0.01).结论 SPK1基因转移能够促进腹腔间皮细胞的增殖和迁移,并有效预防术后肠粘连的发生.该研究有望为预防术后肠粘连提供一种新的策略.     

Halofuginone--an inhibitor of collagen type I synthesis--prevents postoperative formation of abdominal adhesions.

OBJECTIVE: To evaluate the effects of halofuginone, a specific inhibitor of collagen type I synthesis, on the postoperative formation of abdominal adhesions in rats. SUMMARY BACKGROUND DATA: Postoperative adhesions remain the leading cause of small bowel obstruction in the Western world. Surgical trauma causes the release of a serosanguineous exudate that forms a fibrinous bridge between two organs. This becomes ingrown with fibroblasts, and subsequent collagen deposition leads to the formation of a permanent adhesion. Most of the drugs used have been clinically ineffective, and none has been specific to a particular extracellular matrix molecule. Therefore, there are serious concerns about the toxic consequences of interfering with the biosynthesis of other collagens, other matrix proteins, or vital collagen-like molecules. METHODS: Adhesions were induced by scraping the cecum until capillary bleeding occurred. The adhesions were scored 21 days later. Halofuginone was either injected intraperitoneally (1 microg/25 g body weight) every day, starting on the day of operation, or added orally at concentrations of 5 or 10 mg/kg, starting 4 days before the operation. Collagen alpha1(I) gene expression was evaluated by in situ hybridization, total collagen was estimated by Sirius red staining, and collagen type III was detected by immunohistochemistry. RESULTS: The adhesions formed between the intestinal walls were composed of collagen and were populated with cells expressing the collagen alpha1(I) gene. Regardless of the administration procedure, halofuginone significantly reduced the number and severity of the adhesions. Halofuginone prevented the increase in collagen alpha1(I) gene expression observed in the operated rats, thus reducing collagen content to the control level. In fibroblasts derived from abdominal adhesions, halofuginone induced dose-dependent inhibition of collagen alpha1(I) gene expression and collagen synthesis. Collagen type III levels were not altered by adhesion induction or by halofuginone treatment. CONCLUSIONS: Upregulation of collagen synthesis appears to have a critical role in the pathophysiology of postoperative adhesions. Halofuginone, an inhibitor of collagen type I synthesis, could be used as an important tool in understanding the role of collagen in adhesion formation, and it may become a novel and promising antifibrotic agent for preventing postoperative adhesion formation.     

奥曲肽联合透明质酸钠预防兔术后腹膜粘连的疗效评价

目的: 观察奥曲肽联合透明质酸钠预防兔术后腹膜粘连的效果。方法:建立兔术后腹膜粘连模型,然后分为4组：（1）术中不用药物处理设为模型对照组;（2）关腹前局部涂抹透明质酸钠设为透明质酸钠组;（3）关腹前腹腔内注射奥曲肽设为奥曲肽组;（4）关腹前局部涂抹透明质酸钠同时腹腔内注射奥曲肽设为联合组。术后14d剖腹观察,判定腹膜粘连程度等级。结果:4组粘连发生率比较无统计学意义(χ2＝3.51, P>0.05);联合组重度粘连发生率(8.3%)显著低于其它3组（分别为66.7%,33.3%,25.0%）(均P<0.01)。奥曲肽组和透明质酸钠组两组的粘连级别近似（P> 0.05）。结论:奥曲肽和透明质酸钠均可减轻实验性腹膜粘连的程度和重度腹膜粘连发生率,两者合用其作用更明显,表明两药合用具有降低粘连的协同作用。     

Effective prevention of adhesions with hyaluronate

HYPOTHESIS: Hyaluronate sodium in the form of a bioresorbant membrane reduces the development of intra-abdominal adhesions frequently found after implantation of synthetic mesh in the context of surgical hernia repair. DESIGN: The effect of hyaluronate on the formation of adhesions was evaluated when applied laparoscopically as a bioresorbant membrane to protect the peritoneal surface of a synthetic mesh. SETTING: Experimental animal model. INTERVENTIONS: A peritoneal defect 5 cm in diameter was bilaterally created in the abdominal wall of each of 9 pigs by laparoscopy. A polypropylene mesh was fixed with clips onto these defects on both sides. In each of the animals, only on one side, the synthetic mesh was also covered by a hyaluronate membrane. MAIN OUTCOME MEASURES: The incidence and severity of adhesions (grade 0-4, where 0 indicates no adhesion; 1, filmy avascular adhesions; 2, vascular adhesions; 3, cordlike fibrous adhesions; and 4, plain fibrous adhesions) were determined after 45 days, comparing treated and untreated sides by autopsy results and histological features. RESULTS: Adhesions, mainly grades 3 and 4, occurred in 7 of the 9 animals in those meshes not covered by hyaluronate; 2 untreated animals did not develop adhesions. On the other hand, only 1 of the 9 animals developed adhesions (grade 2) at the mesh concealed by the hyaluronate membrane. CONCLUSIONS: The bioresorbant hyaluronate membrane significantly reduced the formation of peritoneal adhesions (1-sided sign test, P<.05) induced by the insertion of a polypropylene mesh, when compared with the contralateral implants not protected by hyaluronate. Thus, hyaluronate membranes are efficient for reducing the incidence of peritoneal adhesions.     

Practical Limitations of Bioresorbable Membranes in the Prevention of Intra-Abdominal Adhesions

Introduction  Intra-abdominal adhesions are a significant source of postoperative morbidity. Bioresorbable barriers composed of hyaluronic acid and carboxymethylcellulose (HA/CMC) reduce adhesion formation by physically separating injured or healing peritoneal surfaces. To assess whether the efficacy of a physical barrier can extend beyond the site of application, we evaluated the effectiveness of an HA/CMC barrier in preventing adhesions distal to the site of placement. Methods  Adhesions were induced in rats by creating peritoneal ischemic buttons on either side of a midline incision. An HA/CMC barrier (Seprafilm™ Genzyme) was intraoperatively placed either under the midline incision, unilaterally over half the ischemic buttons, or bilaterally over all ischemic buttons. Control buttons received no HA/CMC. On day 7 adhesions were scored. In similar experiments, peritoneal fluid was collected at 24 h to assess the effects of HA/CMC on tissue plasminogen activator activity. Results  Placement of HA/CMC under the midline incision did not reduce adhesion formation to distal ischemic buttons (72 ± 7%) compared to controls (80 ± 8%). Unilateral placement of HA/CMC significantly (p < 0.05) reduced adhesion formation to those ischemic buttons over which the barrier was applied (35 ± 7%) compared to both contralateral (83 ± 9%) and control (80 ± 8%) ischemic buttons. The bilateral application of HA/CMC also significantly (p < 0.05) reduced adhesion formation to all ischemic buttons compared to controls (22 ± 7% vs. 66 ± 7%, respectively). HA/CMC did not affect peritoneal tPA activity. Conclusions  Effective adhesion reduction by the physical barrier HA/CMC appears to be limited to the site of application in this rat model. Despite the presence of a bioresorbable membrane at predicted sites of adhesion formation in the peritoneal cavity, adhesions readily form to distal unprotected sites. Presented, in part, at the 49th Annual Meeting of The Society for Surgery of the Alimentary Tract, May 17–21, 2008, San Diego, CA, USA This work was supported in part, by the Smithwick Endowment Fund to the Department of Surgery at Boston University School of Medicine.     

The role of oral fluvastatin on postoperative peritoneal adhesion formation in an experimental rat model

Background: Postoperative peritoneal adhesions are a momentousness complication after abdominal surgery. Although varied means have been used to prevent and treat adhesions, the effects have not been satisfactory. Fluvastatin, a HMG-CoA reductase inhibitors, exhibits a variety of pharmacological effects. Aim of this study was to evaluate the effect of fluvastatin on postoperative peritoneal adhesion formation.

Methods: Seventy-five male Wistar rats weighting 220–250g were randomly assigned equally to three groups. Group A was given sham operation without treatment, Group B was the model group in which postoperative peritoneal adhesion model was created without medication, and Group C was given oral fluvastatin treatment after postoperative peritoneal adhesion model created. After laparotomy on day 7, macroscopic and pathological assessment were evaluated, IL-1β and t-PA in plasma were performed to measure, and tissue samples were taken to measure MMP-9 protein.

Results: There were significant differences between the groups on adhesion grade (p?p?Conclusion: Oral fluvastatin application could reduce formation of intra-abdominal adhesion by promoting expression of MMP-9 level, lowering the levels of IL-1β and increasing the activity of t-PA after abdominal surgery.