Postoperative Intraperitoneal Adhesion Formation Research Articles

The Inhibitory Effects of Naringin in a Rat Model of Postoperative Intraperitoneal Adhesion Formation.

Background Many attempts have been made to inhibit the formation of postoperative intraperitoneal adhesions, but the results have been discouraging. Therefore, the identification of effective preventative measures or treatments is of great importance. In this study, the substantial potential of naringin (NG) to reduce peritoneal adhesions was validated in a rat model. Materials and Methods A rat peritoneal adhesion model was established by abrasion of the cecum and its opposite intraperitoneal region under aseptic surgical conditions. After the operation, three groups of NG-treated rats were given 2 mL of NG by gavage at different concentrations (40, 60, or 80 mg/kg/d). The sham, control, and hyaluronan (HA) groups were given equal volumes of normal saline daily. On the 8th day, all rats were sacrificed 30 min after the administration of an activated carbon solution (10 mL/kg) by oral gavage. Intraperitoneal adhesion formation was adequately evaluated by necropsy, hematoxylin and eosin (HE) staining, Sirius red staining, immunofluorescence staining, enzyme-linked immunosorbent assays, and reactive oxygen species (ROS) probes. The gastrointestinal dynamics of the rats were assessed on the basis of a small intestinal charcoal powder propulsion test and the detection of motilin and gastrin levels in serum. Results Intraperitoneal adhesions were markedly reduced in the group of rats receiving high-dose NG. Compared with the control group, the high-dose NG group showed clear reductions in inflammatory reactions, oxidative stress, collagen deposition, and fibroblast formation in the adhesion tissue and enhanced gastrointestinal dynamics (P < 0.05). Conclusion NG alleviated the severity of intraperitoneal adhesions in a rat model by reducing inflammation, oxidative stress, collagen deposition, and fibroblast formation, highlighting the potential of NG as a drug candidate to prevent postoperative peritoneal adhesion formation.

Effect of intra-abdominal administration of ascites fluid on postoperative peritoneal adhesion in rat model: A randomized controlled trail

IntroductionIntra-abdominal adhesions are typically found after the most surgical procedures. Normally, most adhesions are asymptomatic; however, few individuals experience postoperative adhesion-related problems such as small bowel obstruction, pelvic pain, infertility, or other complications. We aimed to evaluate the preventive effect of the ascites fluid for postoperative peritoneal adhesions in rat models. Material and methodsThis experimental trial was conducted in Sixty Syrian male rat randomly assigned to six groups of 10 animals each as follows: control (group 1&4); normal saline (group 2&5): 2 mL of normal saline was poured into the peritoneal cavity; and case (group 3&6): 2 mL ascites fluid was poured into the peritoneal cavity. All animals in the six groups underwent laparotomy and measurable serosal injury were created with a standard technique. 10 and 30 days after initial surgery, the rats underwent another laparotomy in groups 1, 2, 3 and 4, 5, 6, respectively to assess macroscopic and microscopic adhesions, which were scored by an examiner who was blind to the animals̕ group assignment. Data analyzed by SPSS version 18, using the kruskal Wallis and Bonferroni-corrected Mann-Whitney U tests. P-values of less than 0.05 were considered significant. ResultsThe mean scores of both microscopic and macroscopic adhesion were significantly different between all the groups (P < 0.05). Total macroscopic and microscopic adhesion scores were significantly lower in the ascites fluid treatment than in the control (P = 0.0001) or the normal saline (P < 0.001) group. There was no significant difference between adhesion intensity 10 and 30 days after laparotomy (P > 0.05). ConclusionsAscites fluid can decrease the possibility of post-operative intraperitoneal 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.

Prevention by rat amniotic fluid of adhesions after laparatomy in a rat model

Background Adhesion formation after abdominal surgery (especially multiple operations) is still a major cause of morbidities such as infertility, pain, bowel obstruction, difficult reoperation and other complications. Our aim was to investigate the ability of rat amniotic fluid to prevent adhesion formation after laparatomy in rats. Methods This experimental trial was conducted in 20 pregnant rats randomly assigned to two groups of 10 animals each. Measurable serosal and intestinal injuries were created with a standard technique. Rats in both groups underwent laparatomy and hysterectomy. Then amniotic fluid was poured into the abdominal cavity of animals in the case group. All animals were operated on 4 weeks after initial surgery to assess adhesions, which were scored by an examiner who was blind to the animals’ group assignment. Results The frequency of severe adhesions was 30% in the control group and 0% in the intervention group. Total adhesion scores were significantly lower in the amniotic fluid treatment group than in the control group ( P = 0.002). Conclusions Rat amniotic fluid can decrease the likelihood of post-operative intraperitoneal adhesion formation.

The preventive effect of sodium hyaluronic acid solution and crosslinked hyaluronic acid mixture on postoperative intraperitoneal adhesion formation in rats

The preventive effect of sodium hyaluronic acid solution and crosslinked hyaluronic acid mixture on postoperative intraperitoneal adhesion formation in rats

Effect of bevacizumab on postoperative adhesion formation in a rat uterine horn adhesion model and the correlation with vascular endothelial growth factor and Ki-67 immunopositivity

We investigated whether adhesion formation is prevented by the inhibition of angiogenesis in a rat uterine horn adhesion model. A single-dose of bevacizumab was effective in preventing postoperative intraperitoneal adhesion formation among 30 Wistar albino rats that underwent serosal injury by use of a standard technique after laparotomy with intraperitoneal bevacizumab.

Preventing intraperitoneal adhesions with atorvastatin and sodium hyaluronate/carboxymethylcellulose: a comparative study in rats

Objectives The aim of this study was to compare the effectiveness of atorvastatin with the sodium hyaluronate/carboxymethylcellulose (HA/CMC, Seprafilm; Genzyme; Genzyme Biosurgery Corporation, Cambridge, MA) in preventing postoperative intraperitoneal adhesion formation in rats. Methods Sixty Wistar rats underwent a laparotomy, and adhesions A were induced by cecal abrasion. The animals were divided into 4 groups: group 1, control A; group 2, (A + atorvastatin); group 3, (A + HA/CMC), and group 4, (A + atorvastatin + HA/CMC). The atorvastatin (groups 2 and 4) and HA/CMC (groups 3 and 4) were administered intraperitoneally before the abdominal wall was closed. After 14 days, adhesions were classified by 2 independent surgeons. Results The adhesion scores (mean ± standard deviation) for groups 1, 2, 3, and 4 were 2.93 ± .59, 1.85 ± 1.07, 1.80 ± .86, and 1.93 ± .70, respectively. The differences in adhesion scores among all 3 preventive groups (groups 2, 3, and 4) were statistically significant when compared with the control group ( P = .005, P = .002, and P = .009, respectively). Conclusions These data suggest that atorvastatin, administered intraperitoneally, is as effective as HA/CMC without an expectable additive effect in preventing postoperative adhesions in rats.

Prevention of peritoneal adhesions by intraperitoneal administration of vitamin E and human amniotic membrane

Background Our objective was to evaluate the comparative effectiveness of intraperitoneally administered vitamin E and human amniotic membrane in preventing postoperative intraperitoneal adhesion formation. Material and Methods 75 Wistar-albino rats were separated into 5 groups: Group 1 (control), Group 2 (intraperitoneal olive oil, the diluent of vitamin E), Group 3 (Intraperitoneal vitamin E diluted in olive oil), Group 4 (Amniotic membrane group) and Group 5 (Amniotic membrane and Intraperitoneal vitamin E diluted in olive oil). The same experimental method, consisting of cecal abrasion and ligature of the adjacent parietal peritoneum, was used in all rats to produce adhesions. Relaparotomy was performed on the 15th postoperative day. intra-abdominal adhesions were scored according to macromorphological characteristics and adhesion-carrying tissues underwent standard histologic examination. Inflammation, vascularization and fibrosis in granulation sites were graded in all samples. The results were analyzed using a Mann–Whitney- U test. Results In terms of inflammation, neovascularization and fibrosis scores obtained by histology and macromorphologic adhesion scores. There were no significant differences between Groups 1 and 2 ( p = 0.176). The results of Groups 3, 4 and 5 showed a significant difference when compared with both Group 1 and 2 ( p = 0.001). The difference between Groups 3, 4 and 5 were not significant with respect to these 4 parameters. Conclusion Intraperitoneal vitamin E and amniotic membrane treatment were both effective in the prevention of peritoneal adhesions. The combination of these agents did not produce a synergistic effect. Easy applicability of the intraperitoneal administration of vitamin E was its major advantage.

The preventive effect of Met-RANTES on postoperative intraperitoneal adhesion formation in the rat model

Chemokines are proinflammatory proteins that participate in immune and inflammatory responses through chemoattraction and leukocyte activation. The chemokine antagonist Met-RANTES (Regulated upon Activation Normal T cell Expressed and Secreted) has been shown to be efficacious in decreasing inflammation in several animal disease models. The purpose of this study was to investigate the effects of administration of Met-RANTES on intra-abdominal adhesion formation after abdominal operation. A 42 and 4-month-old female Wistar-Albino rats were subjected to standardized lesions by cauterization of the cecum and uterine horn. They were divided randomly into 3 groups containing 14 rats each: group 1 (control), operative procedure without further treatment; group 2 (Seprafilm), operative procedure with an antiadhesive membrane; 2 x 1 cm of Seprafilm was interposed beneath the peritoneal incision, and group 3 (Met-RANTES), operative procedure with the chemokine antagonist Met-RANTES. The extent and severity of adhesions at the operative site were evaluated. Light microscopic examination was performed to determine semiquantitative scores of VEGF expression. Rats in the control group formed extensive adhesions. In comparison with the control group, the adhesion scores were significantly lower in the 2 other groups. The immunohistochemical grading scores of vascular endothelial growth factor correlated closely with the total adhesion scores and were less in groups 2 and 3 (P < .005). Selective chemokine suppression with Met-RANTES seems to decrease rates, extent, and severity of postoperative intraperitoneal adhesions.

Preventing intraperitoneal adhesions with vitamin E and sodium hyaluronate/carboxymethylcellulose: a comparative study in rats

To compare the effectiveness of intraperitoneally administered vitamin E with the sodium hyaluronate/carboxymethylcellulose membrane (HA/CBMC) in preventing postoperative intraperitoneal adhesion formation. Sixty Wistar rats underwent a laparotomy and adhesions were induced (IA). The animals were divided into four groups: group 1, control (IA); group 2 (IA + Vitamin E): group 3 (IA+HA/CBMC) and group 4 (IA+ Vitamin E + HA/CBMC). The Vitamin E (groups 2 and 4) and HA/CBMC (groups 3 and 4) were administered intraperitoneally before the abdominal wall was closed. After 30 days, adhesions were classified by an independent surgeon. Three animals died; one from group 3 and two from group 4. All control animals had substantial adhesions compared with unsubstantial adhesions observed in 11/15 in group 2 (P = 0.000), 11/14 in group 3 (P = 0.001), and 10/13 in group 4 (P = 0.000). Vitamin E, administered intraperitoneally, is as effective as HA/CBMC in preventing postoperative adhesions.

Postoperative intraperitoneal adhesion pathophysiology

Aside from the normal 'ad integrum' peritoneal regeneration, the postoperative intraperitoneal adhesion formation process may be considered as the pathological part of peritoneal healing following any injury, particularly a surgical one. Despite a large body of clinical and experimental studies, its pathophysiology remains controversial. Moreover, a better understanding of the pathophysiological events and of the medical and surgical factors involved in the adhesion formation process is pivotal in any attempt to control this very frequent phenomenon and its serious consequences.

Protective effect of aminoguanidine against oxidative stress in an experimental peritoneal adhesion model in rats

Postoperative intraperitoneal adhesion formation is a major cause of intestinal obstruction, pain and infertility. This experimental study was designed to evaluate the degree of adhesion formation and peritoneal tissue levels of malondialdehyde (MDA), reduced glutathione (GSH) and total nitrite and nitrate (NO) and the effect of aminoguanidine (AG) on these metabolite values after postoperative intraperitoneal adhesion formation in rats. A total of 21 adult male Wistar albino rats were randomly divided into three groups. Control rats were untreated; the AG group received AG 200 mg kg(-1) i.p. for 10 consecutive days intraperitoneally after surgery. The sham group was given 0.9% NaCl. The rats were killed on postoperative day 10. The peritoneal tissues were harvested to determine the tissue levels of MDA, GSH, and NO activity. For light microscopic evaluation, the cecum was removed. Adhesion formation scores in the AG group were significantly lower than those of the control and sham groups (p < 0.017, p < 0.026 respectively). In the AG-treated rats, tissue levels of MDA and NO were significantly lower than in the control group (p < 0.017). The levels of GSH in aminoguanidine-treated rats were significantly higher than those of the control group (p < 0.01). The severity of the inflammation was more prominent in the control group compared with the AG-injected rats. The results demonstrate that in this experimental model, intraperitoneal administration of aminoguanidine decreases the incidence and extent of peritoneal adhesions and causes a decrease in MDA and NO and an increase in GSH values.

The effect of intravenous aprotinin (Trasylol) on intraperitoneal adhesion formation in the rat.

A randomized controlled trial to assess the effect of intravenous Trasylol on postoperative intraperitoneal adhesion formation has been performed in rats. Before undergoing a standard left colonic resection, animals received i.v. Trasylol 10 000 KIU. This dose was repeated 8-hourly for 3 days postoperatively. Control animals received saline placebo. The mean percentage circumference of the anastomosis covered with adhesions in the Trasylol group animals was 20.86 +/- 6.08 compared with 45.24 +/- 5.97 in the control group (P less than 0.01). Significantly more animals treated with Trasylol were completely free of adhesions than those receiving saline. Bursting pressures did not differ between the two groups. Intravenous Trasylol clearly inhibits intraperitoneal adhesion formation in this model.

Protective effect of melatonin against oxidative stress on adhesion formation in the rat cecum and uterine horn model

This experimental study was designed to evaluate the degree of adhesion formation and peritoneal tissue levels of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) and the effect of melatonin on these metabolites in a postoperative intraperitoneal adhesion formation model in rats. Thirty adult female Wistar albino rats were subjected to standardized lesions by cecal and uterine horn abrasion and were randomly divided into three groups. Control rats were treated with 5% ethanol. Melatonin treated rats received 4 mg/kg melatonin before closure and for 10 consecutive days intraperitoneally after surgery. Rats in the sham operation group underwent a surgical procedure similar to the other groups however the peritoneal abrasion was not performed. On postoperative day 10 relaparatomy was performed. After the assessment of the adhesions, the rats in each group were sacrificed and peritoneal tissues were harvested to determine the tissue levels of MDA, GSH and NO activity. Adhesion formation scores in the melatonin group were significantly lower than that of control and sham group ( p < 0.01 and p < 0.02, respectively). Tissue levels of MDA and NO were significantly lower in the melatonin treated rats when compared with control and sham groups. The levels of GSH in the melatonin treated rats were significantly higher than those of control and sham groups ( p < 0.01). The results demonstrate that in this experimental model, intraperitoneal administration of melatonin decreases the extent of peritoneal adhesions and causes a decrease in MDA and NO and an increase in GSH levels.

The prevention of postoperative intraperitoneal adhesions by tranilast: N-(3',4'-dimethoxycinnamoyl)anthranilic acid.

The development of postoperative intraperitoneal adhesions continues to be a major concern for surgeons. The purpose of this study was to establish a postoperative adhesion model in rats, and to assess the effectiveness of tranilast (N-(3',4'-dimethoxycinnamoyl)anthranilic acid) in preventing postoperative adhesion formation. The adhesion model was established in 12 male Donryu rats. This involved two essential factors, drying and bleeding. Another 22 male Donryu rats were used to study the prevention of intraperitoneal adhesions. Tranilast was administered orally pre- and postoperatively. Adhesion strength was evaluated by grading, and basic fibroblast growth factor (bFGF) and transforming growth factor-beta-1 (TGF-beta1) concentration were measured. Postoperative intraperitoneal adhesions were seen in all rats, but the adhesions in the tranilast group were significantly less severe than those in the control group. Serum bFGF and TGF-beta1 levels in the tranilast group were lower at the time of surgery than those in the control group, and bFGF levels were lower at the endpoint of this study in the tranilast group than in the control group. The TGF-beta1 levels at the end-point did not differ between the two groups. These findings demonstrated that tranilast significantly reduced postoperative intraperitoneal adhesion formation.

The effect of L‐arginine and pentoxifylline on postoperative adhesion formation

Postoperative intraperitoneal adhesion formation is a major cause of infertility, pain, intestinal obstruction, and subsequent intraoperative complication. We investigated the effects of L-arginine and pentoxifylline for preventing postoperative adhesion in rats. Forty Sprague-Dawley rats were subjected to a standardized lesion by serosal trauma of the uterine horn and parietal peritoneal defect. The agents were administered intraperitoneally at the end of surgery. The rats were assigned randomly into control (saline treated), L-arginine, pentoxifylline and L-arginine with pentoxifylline groups. Two weeks after surgery, a second laparotomy was performed and the extent of adhesion formation was determined. The data were analyzed by Mann Whitney U test. In L-arginine and pentoxifylline administered groups, adhesion formation scores were significantly lower than the control group (p<0.05). However, the efficacy of L-arginine used together with pentoxifylline is not superior to those of L-arginine or pentoxifylline alone. This study showed that L-arginine and pentoxifylline administered at the end of surgery reduced adhesion formation.

Endogenous versus Exogenous IL-10 in Postoperative Intraperitoneal Adhesion Formation in a Murine Model

Background: Modulation of the immune response to peritoneal injury may prevent postoperative adhesion formation. Exogenous interleukin-10 (IL-10) limits postoperative adhesion formation. The objective of the present study is to determine (I) the IL-10 dose most effective at adhesion prevention, (II) the presence of endogenous IL-10 in peritoneal fluid, and (III) the ability of an anti-IL-10 monoclonal antibody to modify postoperative intraperitoneal adhesion formation. Materials and methods: Within parts I, II, and III of the study 6-week-old Swiss Webster mice were randomized to have no surgery or to undergo a standardized adhesion-inducing peritoneal injury. Animals were further randomized to different dosing schedules of IL-10 (10 ng/kg to 100 μg/kg; part I), different times of euthanasia and peritoneal lavage after surgery (part II), or intraperitoneal (ip) treatment with phosphate-buffered saline vehicle (1 ml), IL-10 (1 μg/kg), or anti-IL-10 (1 μg/kg; part III). All ip injections were given immediately after surgery and then every 24 hr for a total of four injections. Animals were sacrificed 7 days after surgery and adhesion formation was assessed. Results: Maximal adhesion-limiting effects of exogenous IL-10 were reached at doses of 1 μg/kg. Mean detectable endogenous IL-10 levels in the peritoneal fluid varied from 145 to 220 pg/ml throughout the postoperative course. There were significant (P< 0.0005) differences in adhesion scores between mice treated with IL-10 (3.39; 95% CI 0.39–6.39) or PBS postoperatively (7.46; 95% CI 5.28–9.64), untreated surgical control animals (5.98; 95% CI 2.55–9.41), or anti-IL-10-treated animals (10.11; 95% CI 8.50–11.72). Conclusion: Interleukin 10 is effective at reducing postoperative intraperitoneal adhesion formation. Low levels of endogenous IL-10 are detectable in peritoneal fluid throughout the postoperative course, not correlating with adhesion scores. Anti-IL-10, when administered daily postoperatively in pharmacologic doses, does not appear to significantly increase postoperative adhesion formation. This puts into question if endogenous IL-10 production indeed plays a role in nonadhesiogenic peritoneal healing.

Preventing postoperative intraperitoneal adhesion formation with Polyactive™, a degradable copolymer acting as a barrier

In this study a degradable barrier, composed of a poly(ethyleneglycol) and poly(butyleneterephthalate) copolymer (1000 Polyactive™ 55/45), was investigated for the prevention of postoperative adhesion formation. Three different designs of polymer films were used in a standardized rat adhesion model in order to investigate which barrier form would be most efficacious in reducing adhesion formation. Neither non-porous nor porous film reduced the adhesion formation as compared with control experiments. A bilayered film, however, composed of a porous underlayer and a non-porous toplayer, reduced the adhesion formation significantly compared with control animals without a barrier. In the case of adhesion formation with this bilayered film the adhesions were limited to areas that were macroscopically not covered, either due to fractures in or detachment of the barrier. Subsequently a more malleable porous/dense film was designed which did not fracture and reduced the adhesion formation significantly compared with animals treated with Interceed™, even though some barriers detached as in the first experiment. The porous/dense Polyactive™ barrier seems to be a promising adjuvant in the reduction of postoperative adhesion formation, although further research is needed to accomplish better attachment of the barrier.

Interleukin 10: ability to minimize postoperative intraperitoneal adhesion formation in a murine model

To determine the ability of interleukin 10 (IL-10) to suppress postoperative intraperitoneal adhesion formation. Randomized, controlled trial. University animal research facility. Six-week-old Swiss Webster mice undergoing a standardized intraperitoneal operative procedure. Animals were randomized to "surgery" or "no surgery" and then further randomized to receive intraperitoneal injections of 1 mL phosphate-buffered saline (PBS) or 1 microgram/kg IL-10 in 1 mL PBS. Vehicle-only doses were given immediately after surgery and then every 24 hours for a total of four injections. Interleukin 10 injections were similarly given but with an added preoperative injection 30 minutes before surgery in one half of the animals. Adhesion formation. Animals treated with vehicle or IL-10 but not undergoing surgical intervention had no intraperitoneal adhesions. Animals undergoing surgery who were treated with IL-10, with or without a preoperative dose, had significantly lower postoperative adhesion scores than did control animals who postoperatively received PBS only. Interleukin-10 is effective at limiting postoperative intraperitoneal adhesion formation with minimal evident systemic side effects.

Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation in the rat model

The aim of this study was to determine the effectiveness of hyaluronic acid solution in preventing intraperitoneal (IP) adhesions. The study design was prospective, randomized and blinded and involved 83 rats. Measured serosal injury was inflicted using a CO2 laser on the right uterine horn of the rat. Animals randomized to groups 1 and 2 received either 0.4% hyaluronic acid or its diluent phosphate-buffered saline (PBS) intraperitoneally before and after the injury. In groups 3 and 4, the same solutions were used only after the injury. Postoperative adhesions were assessed at second-look laparotomy. Histologic assessment of the fresh laser injury was carried out on uteri pretreated with hyaluronic acid, PBS, or nothing. Pretreatment with hyaluronic acid was associated with a significant reduction in postoperative adhesions and a significantly decreased crater depth. Hyaluronic acid appears to reduce postoperative IP adhesion formation by coating the serosal surfaces and decreasing the extent of initial tissue injury.