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.     

一氧化氮对术后腹膜粘连作用的实验研究

目的研究一氧化氮 (NO)在预防大鼠术后腹膜粘连中的作用。方法 40只大鼠统一制作腹膜粘连模型 ,随机分为对照组和左旋精氨酸组。术后分别腹腔内注射 0 9%NaCl和左旋精氨酸 ,连续 3d。术后 3d随机抽取部分大鼠血样测定NO ,同时取材作病理检查。其余大鼠 2周后乙醚处死开腹观察并记录粘连情况。结果对照组的粘连分级 (3 7± 0 7)重于左旋精氨酸组 (0 9±1 1) ,t=8 6 ,P <0 0 1。对照组血中NO的水平为 (13 9± 1 1) μmol/L ,低于左旋精氨酸组 (32 2± 2 8)μmol/L ,t=2 0 4,P <0 0 1。左旋精氨酸组粘连组织中诱导型一氧化氮合酶 (iNOS)的免疫组化染色分级为 2 5± 0 7强度高于对照组 (0 8± 0 4) ,t=11 1,P <0 0 1。结论一氧化氮在腹膜粘连的预防中起重要作用     

The judgement of adhesion formation following laparoscopic and conventional cholecystectomy in an animal model

INTRODUCTION: The development of postoperative adhesions remains an almost inevitable consequence of visceral and gynaecologic surgery, appearing in 50-95% of all patients. Although decreased adhesion formation is one of the accepted advantages of laparoscopic surgery, only a small number of prospective studies have been done to support this claim. AIMS OF THE STUDY: To evaluate the extent of postoperative adhesion formation after laparoscopic and open cholecystectomy. MATERIAL AND METHOD: 60 experimental laparoscopic cholecystectomies (LC) were performed by qualified surgeons in dogs with the aim to acquire the laparoscopic technique. To assess the relation between the complications during the operation (bleeding, injury to the liver substance or gallbladder perforation) and the formation of adhesions, the surviving animals were divided into 4 groups according to the complications occurred. The assessment of the results was made by second--look laparoscopy 4 weeks following LC using the adhesion index. As a control group open cholecystectomy was then performed in 5 dogs without intraoperative complications. RESULTS: No adhesion formation was observed in the groups where no intraoperative complications occurred. In all the cases where bleeding or injury to the liver bed occurred adhesion formation occurred. No adhesion formation was observed in case of gallbladder perforation. In all the animals of the control group adhesion formation was observed. CONCLUSION: It seems that LC has a reduced rate of adhesion formation when compared with the open technique. Complications such as bleeding or injury to the liver substance during LC can enhance adhesion formation. No adhesion formation can be mentioned in relation with gallbladder perforation when the laparoscopic technique is applied.     

The neurokinin 1 receptor regulates peritoneal fibrinolytic activity and postoperative adhesion formation

Background

Intra-abdominal adhesions are a common source of postoperative morbidity. Previous studies in our laboratory have shown that a neurokinin 1 receptor antagonist (NK-1RA) reduces abdominal adhesion formation and increases peritoneal fibrinolytic activity. However, the cellular pathway by which the antagonist exerts its effects is unclear, as cultured peritoneal mesothelial cells exposed to the NK-1RA show increases in fibrinolytic activity despite having very low expression of neurokinin 1 receptor (NK-1R) messenger RNA and protein. Our aim was to determine whether the NK-1R plays an essential role in the adhesion-reducing effects of the NK-1RA, or if the NK-1RA is acting independently of the receptor.

Methods

Homozygous NK-1R knockout mice and age matched wild-type mice underwent laparotomy with cecal cautery to induce adhesions. At the time of surgery, mice received a single intraperitoneal dose of either NK-1RA (25 mg/kg) or saline alone. Adhesion severity at the site of cecal cautery was assessed on postoperative day 7. In a separate experiment, peritoneal fluid was collected from wild type and NK-1R knockout mice 24 h after laparotomy with cecal cautery and administration of either NK-1RA or saline. Tissue plasminogen activator levels, representative of total fibrinolytic activity, were then measured in peritoneal fluid.

Results

In wild-type mice, NK-1RA administration significantly decreased adhesion formation compared with saline controls. Among the NK-1R knockout mice, there was no significant reduction in adhesion formation by the NK-1RA. Fibrinolytic activity increased 244% in wild-type mice administered NK-1RA compared with saline controls; however, the NK-1RA did not raise fibrinolytic activity above saline controls in NK-1R knockout mice.

Conclusions

These data indicate that the NK-1R mediates the adhesion-reducing effects of the NK-1RA, in part, by the upregulation of peritoneal fibrinolysis, and suggest that the NK-1R is a promising therapeutic target for adhesion prevention.     

Icodextrin reduces postoperative adhesion formation in rats without affecting peritoneal metastasis

BACKGROUND: Peroperative peritoneal trauma activates a cascade of peritoneal defense mechanisms responsible for postoperative adhesion formation. The same cascade seems to play a role in the process of intra-abdominal tumor recurrence. Icodextrin is a glucose polymer solution that is absorbed slowly from the peritoneal cavity, allowing prolonged "hydroflotation" of the viscera, thereby decreasing adhesion formation. This study evaluated the adhesion-preventing properties of icodextrin and its effect on peritoneal metastasis. METHODS: Reproducible rat models of peritoneal trauma were used, allowing semiquantitative scoring of adhesion formation or tumor load. In one experiment, peritoneal trauma was inflicted; one group was treated by peroperative intra-abdominal instillation of 7.5% icodextrin, one by instillation of RPMI (placebo), and one had no instillate (controls). In another experiment involving a different model of peritoneal trauma, the coloncarcinoma cell line CC531 was injected intraperitoneally to induce tumor load, again using these three groups. RESULTS: Treatment of peritoneally traumatized rats with icodextrin caused a 51% reduction in postoperative adhesion formation ( P < .001). However, peroperative intra-abdominal treatment with icodextrin did not affect intraperitoneal tumor cell adhesion and growth of free intra-abdominal tumor cells in rats with this model of severe peritoneal trauma. CONCLUSION: A 7.5% icodextrin solution is effective in reducing postoperative adhesions without promoting tumor recurrence and therefore may prove useful and safe in oncologic surgery.     

The influence of intraoperative complications on adhesion formation during laparoscopic and conventional cholecystectomy in an animal model

BACKGROUND: The aim of this study was to evaluate the extent of postoperative adhesion formation after laparoscopic and open cholecystectomy. MATERIALS AND METHODS: Qualified surgeons performed 60 experimental laparoscopic cholecystectomies (LC) in dogs with the aim to acquire the laparoscopic technique. To assess the relation between the complications during the operation (bleeding, laceration of the liver bed, or gallbladder perforation) and the formation of adhesions, surviving animals were divided into four groups according to the type of complication occurred. Assessment of the results was made by second-look laparoscopy 4 weeks after LC using the adhesion index (AI; score range, 0-4). The animals then were killed so the extent of adhesion formation could be measured. As a control, open cholecystectomy was performed in 15 dogs without intraoperative complications. The Mann-Whitney rank-sum test and Dunn's method were used for statistical analysis. RESULTS: No adhesion formation or intraoperative complications were registered in the laparoscopic group I. In all the cases wherein bleeding or laceration of the liver bed occurred and was managed with electrocoagulation, adhesions formed. Adhesion formation in these groups was significantly higher than in "ideal LC" or cases of gallbladder perforation alone (p < 0.01). All the animals in the control group developed significantly more adhesions than those in the experimental group (p < 0.05). CONCLUSIONS: It seems that LC has a lower rate of adhesion formation than the conventional open technique. Complications such as bleeding or laceration of the liver bed during LC can enhance adhesion formation. No adhesion formation can be mentioned in relation to gallbladder perforation during LC.     

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.     

盆腔粘连形成的研究进展

盆腔粘连是妇科手术后常见的并发症 ,可引起急性复发性肠梗阻、不孕不育、性生活不适等 ,且使临床治疗费用增高。故盆腔粘连形成及治疗的问题越来越引起人们的关注。本文就盆腔粘连形成的机制、预防和处理作一综述。     

白藜芦醇预防大鼠椎板切除术后硬膜外粘连的实验研究

[目的]探讨白藜芦醇对椎板切除术后硬膜外粘连的预防作用。[方法]60只Wistar大鼠行L_2椎板切除术,形成3 mm×3 mm硬膜裸露区,随机平均分为3组。A组:术后给予白藜芦醇药物溶液干预;B组:术后给予生理盐水干预;C组:单纯椎板切除术组。术后6周处死动物并取材,行羟脯氨酸(hydroxyproline hyp)含量分析;肉眼观察硬膜外粘连情况,并行Rydell分级;样品行石蜡包埋并切片后,行免疫组织化学、HE染色。[结果]术后6周A组较B组、C组粘连程度轻,Rydell分级具有统计学意义(P0.05),B组、C组间差异无统计学意义(P0.05);A、B、C三组硬膜外瘢痕组织中羟脯氨酸的含量分别为(27.95±4.88)μg/mg、(42.85±4.57)μg/mg、(43.95±5.73)μg/mg,A组较B组、C组少,差异有统计学意义(P0.05),B组、C组间差异无统计学意义(P0.05);单位成纤维细胞及波形蛋白计数,A组较B组和C组少,差异有统计学意义(P0.05),B组、C组间差异无统计学意义(P0.05)。[结论]白藜芦醇能够良好的预防大鼠椎板切除术后出现的硬膜外粘连,并可抗炎及抑制成纤维细胞增殖。     

The effect of octreotide on postoperative adhesion formation.

OBJECTIVE: To investigate the effect of octreotide, a long-acting analogue of somatostatin, on postoperative adhesion formation, because somatostatin inhibits secretion of some growth factors that have modulatory effects on collagen synthesis. DESIGN: An experimental study. SETTING: Surgical Research and Biochemistry laboratories at Hacettepe University, Ankara, Turkey. SUBJECTS: Male Swiss albino mice. INTERVENTIONS: Both sides of a 5-cm ileal segment from Swiss albino mice were scraped 10 times, and transient ischemia was induced by clamping the segmental artery. Animals were injected subcutaneously with 1 mL/d of saline for 3 days (group 1), a single 5-mL intraperitoneal dose of saline (group 2), subcutaneously with 10 micrograms/kg daily of octreotide for 3 days (group 3) or a single 10 micrograms/kg intraperitoneal dose of octreotide (group 4). In half of the animals repeat laparotomy was performed on postoperative day 5. After adhesions were graded, the scraped ileal segments were excised for determination of hydroxyproline quantity. The same procedure was repeated on postoperative day 14 for the remaining animals. OUTCOME MEASURES: Adhesion grading, hydroxyproline levels. RESULTS: On postoperative day 5, the intraperitoneal octreotide group (group 4) had a significantly lower median adhesion score than groups 1 and 2. On postoperative day 14, both octreotide groups (3 and 4) had a significantly lower median adhesion grading than both saline groups (1 and 2). Hydroxyproline levels of the groups were not significantly different on either day 5 or day 14. CONCLUSION: Octreotide has a beneficial effect in decreasing adhesion formation in the early postoperative period.     

Increased postoperative peritoneal adhesion formation after the treatment of experimental peritonitis with chlorhexidine

Background and aims Chlorhexidine is known as a substance that produces adhesions. However, in an experimental model of peritoneal injury, lavage with chlorhexidine and saline solutions produced a similar number of adhesions. This study was designed to test the hypothesis that chlorhexidine gluconate 0.05% solution used for the treatment of peritonitis increases formation of postoperative peritoneal adhesions as compared to standard lavage with saline solution.Material and methods Forty Wistar rats were randomly allocated to gastric or faecal peritonitis groups. In each group rats were further randomly subdivided into saline or chlorhexidine peritoneal lavage groups. After 30 days the rats were killed and intraperitoneal adhesions were evaluated by adhesion score and grading.Results Adhesion scores were statistically significantly different between saline and chlorhexidine groups in both gastric and faecal peritonitis models. In the faecal peritonitis chlorhexidine group a 20% small bowel intussusception rate was observed, while there were no such complications in the other study groups. The conglomerate of organs formed by dense adhesions was present in 60% of cases when gastric peritonitis was lavaged by chlorhexidine and in only 10% when saline solution was used (P<0.05). Neither chlorhexidine nor saline solutions have caused such dense adhesions in faecal peritonitis.Conclusion Peritoneal lavage with chlorhexidine gluconate 0.05% solution in the treatment of experimental peritonitis results in increased adhesion formation.     

The preventive effect of ambroxol hydrochloride chitosan on postoperative intraperitoneal adhesion formation in a rat model

Background: This study aimed to investigate the effects of ambroxol hydrochloride chitosan reduced the degree of peritoneal adhesion.

Methods: A total of 120 Sprague–Dawley (SD) rats were experimented, group A: the damaged peritoneal was covered with ambroxol hydrochloride chitosan, group B: chitosan membrane only, group C: nothing. Enzyme-linked immunosorbent assay (ELISA), western blotting, and immunohistochemistry (IHC) were used to observe the expression of TNF-α and NF-κB p65.

Results: TNF-α and NF-κB p65 in group A significantly decreased in comparison with the controls. IHC showed TNF-α and NF-κB p65 were significantly down-regulated in group A. Adhesion grade in the treatment group was significantly lower than in controls.

Conclusion: Ambroxol hydrochloride chitosan reduced the degree of peritoneal adhesion.     

The role of oxygen-derived free radicals in peritoneal adhesion formation induced by ileal ischaemia/reperfusion

The effectiveness of superoxide dismutase (SOD), catalase (CAT), dimethyl sulphoxide (DMSO) and allopurinol in prevention of peritoneal adhesion formation induced by complete vascular obstruction and reperfusion of an ileal segment was investigated in rats. The ischaemic period was 30 min. Group A (n = 20) were controls, group B (n = 15) received SOD 15,000 U/kg i.v. and group C (n = 17) the same dose of CAT immediately before induction of ischaemia. In group D (n = 20) DMSO 20 mg/kg was given i.v. 5 min before ischaemia, and group E (n = 20) received allopurinol orally 50 mg/kg daily for 2 days and also 2 hours before ischaemia. Ten days later adhesions had developed in 80% of group A, 40% of group B, 47% of group C and 45% of groups D and E (p less than 0.05). The severity of the adhesions was significantly less in the pretreated groups than in the controls. Oxygen-derived free radicals may be pathogenetically important for such adhesion formation. Xanthine oxidase is the principal source of oxygen radicals after a 30-min period of complete regional intestinal ischaemia.     

Preliminary assessment of postoperative adhesion formation after laser-assisted mesh fixation to the peritoneal surface

OBJECTIVE: This study evaluated the incidence and persistence of adhesions following intraperitoneal onlay mesh fixation with tissue soldering in an experimental model. METHODS: Anesthetized New Zealand white rabbits (n = 21), weighing 2.8-3.2 kg, underwent laparotomy. Controls (group 1 [n = 3]) had 2 x 2 cm Mersilene (Ethicon, Somerville, New Jersey) polyester mesh segments fixed to the peritoneum with staples (USSC, Norwalk, Connecticut). Group 2 (n = 7) rabbits had Mersilene mesh affixed by melting 55% collagen solder using a prototype laser (1.43 micro, 2.5 W CW, 4 mm spot size, 60 degrees C set temperature) over mesh. Group 3 (n = 6) rabbits had Vicryl (Ethicon, Somerville, New Jersey) polyglactin mesh embedded in 60% collagen solder placed onto the peritoneum and fixed with identical laser parameters as group 2. Group 4 (n = 5) rabbits had 55% collagen solder placed and Mersilene pressed into it after melting. Four segments were placed in each experimental animal. Animals were euthanized at 2, 4, or 6 weeks. Adhesions were graded (0 = none; I = filmy adhesions; II = omental; III = bowel adhesions gently lysed; IV = dense adhesions requiring sharp dissection). RESULTS: Grade III adhesions were observed in both control and group 4 animals at 2 weeks, persisting in group 4 animals at 6 weeks, but having lysed in controls at 6 weeks. No adhesions were present in group 3 specimens at any interval. Grade I adhesions were present in group 2 at 2 weeks at exposed mesh areas, and declined in frequency at 6 weeks. Evidence of reabsorption of the polyglactin mesh-solder composite was apparent in the group 3 specimens at 4 weeks, and complete resorption had occurred by 6 weeks postoperatively. DISCUSSION: Laser-assisted solder fixation caused minimal adhesion formation when mesh was covered by solder. Adhesions were observed if Mersilene mesh material was exposed to the abdominal contents. Vicryl mesh-solder composites reabsorbed without inflammation, scarring, or adhesions at the sites of mesh fixation. CONCLUSION: Further development of this technology is warranted.