Prevention Of Postsurgical Adhesion Formation Research Articles

Epigallocatechin-3-O-Gallate-Loaded Poly(lactic-co-glycolic acid) Fibrous Sheets as Anti-Adhesion Barriers.

Epigallocatechin-3-O-gallate (EGCG), the main polyphenolic component of green tea, has a wide range of pharmacological activities, including antioxidant, anti-inflammatory, and anti-fibrotic effects. In this study, EGCG-loaded poly(lactic-co-glycolic acid) (PLGA) sheets were prepared by electrospinning nanofibers and evaluating their potential as tissue-adhesion barriers. EGCG-loaded PLGA (E-PLGA) fibrous sheets were electrospun from a PLGA solution containing 8% (w/v) EGCG. The average diameter of E-PLGA fibers was 397 ± 159 nm, which was comparable to that of pure PLGA fibers (459 ± 154 nm). EGCG was uniformly dispersed in E-PLGA sheets without direct chemical interactions. E-PLGA fibrous sheets showed sustained release of EGCG by controlled diffusion and PLGA degradation. The attachment and proliferation of L-929 fibroblastic cells were significantly (p < 0.05) suppressed in E-PLGA sheets. Furthermore, E-PLGA fibrous sheets did not induce any inflammatory response to J774A.1 macrophages. The anti-adhesion efficacy of E-PLGA fibrous sheets was evaluated in the intraperitoneal adhesion model in rats. Two weeks after surgical treatment, macroscopic adhesion (extent and severity) scores and histopathological tissue responses of E-PLGA fibrous sheets were significantly lower than those of non-treated controls and pure PLGA sheets. The results suggest that the scores are comparable, and in some cases superior, to those of other commercialized tissue-adhesion barriers. In conclusion, our study findings suggest that E-PLGA fibrous sheets may be exploited as potential tissue-adhesion barriers for the prevention of post-surgical adhesion formation.

Application of hyaluronic acid/sodium alginate-based microparticles to prevent tissue adhesion in a rabbit model.

Postsurgical adhesion formation is a concern in every field of surgery. We evaluated the efficacy of hyaluronic acid/sodium alginate-based microparticle anti-adhesive agents (MP) for the prevention of postsurgical adhesion formation in a standardized rabbit model. To evaluate the anti-adhesion effect, a uterus-abdominal wall abrasion model was created in rabbits. On the surface of the injured uterus, an anti-adhesive agent, Interceed(®) or MP, was applied (positive control and study groups, respectively; n = 10 each). In another group of 10 animals, neither agent was applied (negative control group). The adhesion levels were graded 3 weeks after surgery. Acute and chronic toxicity was also evaluated. The grade of adhesion was significantly lower in the MP group than in the negative control and positive control groups. No evidence of acute or chronic toxicity induced by this material was found in blood and tissue analysis. MP shows potential as an effective novel type of resorbable biomaterial to reduce postoperative adhesion. The easy placement and handling of this material make the MP powder attractive as a tissue adhesion barrier.

Prevention of postoperative peritoneal adhesions by O-carboxymethyl chitosan in a rat cecal abrasion model

Post-surgical adhesion formation can result in significant morbidity and mortality. N,O-carboxymethyl chitosan (N,O-CMC) has been previously shown to be effective in the prevention of postsurgical adhesion formation. In this study, we evaluated the ability of O-carboxymethyl chitosan (O-CMC), another chitosan derivative generated by carboxymethylation of chitosan's oxygen centers, to reduce postsurgical adhesion development. Twenty male Sprague-Dawley rats (250 +/- 20 g) were divided into two equal groups: O-CMC group and saline (control) group. All rats underwent a midline laparotomy and the cecum was abraded to cause petechial hemorrhages. Following peritoneal injections of either saline or O-CMC, the incisions were closed. Seven days after surgery, the animals were killed and adhesion formation was scored. Tissue samples from the adhesions were examined histochemically. Adhesion formation was significantly decreased in the O-CMC group (P < .001) in comparison with the control group. Furthermore, significantly less collagen (P < .001) and fewer inflammatory cells and fibroblasts were detected in the O-CMC-treated animals. Additionally, a significantly (P < .05) lower level of TGF-beta1 expression was found in the O-CMC group. O-CMC appears to be effective in the prevention of postoperative peritoneal adhesion formation, which may be attributed to decreased accumulation of inflammatory cells and fibroblasts and reduced collagen synthesis.

Effects of Three Different Types of Anti-adhesive Agents in a Rat Abdominal Wall Defect Model

Purpose: Postsurgical adhesion formation is a significant clinical problem within every surgical specialty. Several adhesion barriers have been developed in the form of solution, membrane or film in an attempt to solve these problems. The purpose of the present study is to compare the efficacy of antiadhesive agents in the prevention of postsurgical adhesion formation in a standardized rat adhesion model. Methods: We examined forty Sprague-Dawley rats, which is a cecal abrasion with partial peritonectomy model. Three treatment groups (Group I: Film-type Surgiwrap Ⓡ , Group II: Solution-type Guardix-sol Ⓡ , Group III: Membrane-type Interceed Ⓡ ), each consists of 10 rats, and a control group of 10 rats were used by saline. Ten days after surgery, the rats were killed, and the levels of adhesion were graded. Immunohistochemical staining for microvessel density (CD34, MVD) and macrophage (ED1) were performed in adhesion tissue. Results: The peritoneum adhesion mean scores are as follows: control group: 2.2±0.78, Group I: 1.0±1.06, Group II: 0.9±0.99, Group III: 0.6±0.84. All treatment groups showed significantly less peritoneum adhesion (P=0.006), while there was no significant difference in each group. The intraperitoneal organs adhesion mean scores are as follows: control group: 2.8±0.91, Group I: 2.6±1.06, Group II: 1.4±0.84, Group III: 1.0±0.81. Group I had no significant difference about intraperitoneal organs adhesion with control group, but Group II and Group III showed less intraperitoneal organs adhesion. The mean numbers of microvessel density are as follows: control group: 42.5±4.83, Group I: 40.8±6.53, Group II: 30.9±6.15, Group III: 15.60±4.37, from which there was a significant difference between Group II and Group III with control group (P＜0.001). The mean numbers of macrophage are as follows: control group: 223.3±33.12, Group I: 211.25±10.96, Group II: 171.60±23.96, Group III: 147.0± 12.22, from which there was a significant difference between Group II and Group III with control group (P＜0.001). Conclusion: In our animal model, three different types of antiadhesive agents (Surgiwrap Ⓡ , Guardix-sol Ⓡ , Interceed Ⓡ ) were effective in adhesion prevention, but Surgiwrap Ⓡ had less antiadhesive effect for intraperitoneal organs adhesion. Membrane-type Interceed Ⓡ had a better effect for microvessel density (MVD) and macrophage than solution-type Guardix-sol Ⓡ . (J Korean Surg Soc 2009;77:7-14)

The comparison of diphenhydramine HCl and Nedocromil sodium in prevention of abdominal postoperative adhesion formation in rat models: An experimental study

Background The purpose of this study was to determine the effects of diphenhydramine HCl and Nedocromil sodium for the prevention of postsurgical adhesion formation in rat model. Methods Sixty adult female rats were anesthetized by 5 mg/kg ketamine hydrochloride. After opening the abdominal wall, a 2 cm 2 peritoneal layer was excised from the left abdominal wall and 10 longitudinal incisions of 2 to 3 cm in length were made on the right parietal peritoneum. The abdominal wall was closed with 4/0 atraumatic continuous nylon sutures. Group I was the control group, group II was given 10 mg/kg diphenhydramine HCl, group III was given 100 mg/kg Nedocromil sodium, and group IV was administered both drugs in the above doses. All the drugs were instilled into the peritoneal cavity after abdominal closure except Nedocromil sodium which was administered in two separate doses 30 min before surgery and just after abdominal closure. Relaparatomy was performed 2 weeks after the initial surgery and abdominal adhesions were scored. Kruskal–Wallis and Mann–Whitney U-test were used for the statistical evaluation. Results The mean ± S.D. (median) of adhesion scores were 2.5 ± 0.90 (2.0), 1.58 ± 0.99 (1.0), 0.92 ± 0.86 (1.0) and 1.75 ± 0.75 (2.0) in group I, II, III and IV, respectively. There were significant differences between the scores of groups I and II ( P = 0.033), groups I and III ( P < 0.001), and groups I and IV ( P = 0.033). Conclusion Both diphenhydramine HCl and Nedocromil sodium reduced postoperative abdominal adhesions separately and in combination with each other in our study. Average score of adhesion formation was lowest in the group that was administered Nedocromil sodium. More research is needed in order to discover any positive effect of these drugs as antiadhesive agents in humans.

Lipiodol™ versus methylene blue for prevention of postsurgical adhesion formation in a rat model

Objective: To determine the effects of intraperitoneal Lipiodol™ and methylene blue in prevention of postsurgical adhesion formation. Study design: Thirty female rats were divided into three equal groups and a standard damage to provoke adhesion formation was made by laparotomy to each of them. Methylene blue and Lipiodol™ was administered intraperitoneally to the first and second groups, respectively; while the third group was taken as control and no additional intervention was made. Adhesions were scored by a second look laparotomy which was made 21 days after the first operation. Results: Adhesion scores of the second group (i.e. Lipiodol™ group) were significantly lower than that of controls. No significant differences were present between any other groups (i.e. methylene blue versus control and methylene blue versus Lipiodol™). Conclusion: Intraperitoneal administration of Lipiodol™ inhibits postsurgical adhesion formation in rats.

Prevention of post-surgical adhesion formation using aspirin in a rodent model: a preliminary report

Prevention of post-surgical adhesion formation using aspirin in a rodent model: a preliminary report

Prevention of post-surgical adhesion formation using aspirin in a rodent model: a preliminary report

Prevention of post-surgical adhesion formation using aspirin in a rodent model: a preliminary report

Effects of SeprafilmU (sodium hyaluranate-based bioresorbable), SepracoatU (0.4% hyaluronic acid), and Ringer's lactate on the prevention of postsurgical adhesion formation in rat models

Forty adult female rats were randomly divided into four groups. Before the standard surgical procedure which consisted of creating a lesion with a lancet over the right uterine horn. Group I received no medication. Ringer's lactate (RL) solution was applied intraperitoneally to Group II at the end of the surgery. Sepracoat solution was applied intraperitoneally to Group III at the onset of the surgery. Group IV randomly received Seprafilm wrapped over the entire right uterine horn. Re-laparotomy was performed 3 weeks later to evaluate the adhesions. The mean adhesion scores were (mean+/-SD) 2.90+/-0.18, 1.00+/-0.36, 0.50+/-0.17 and 0.40+/-0.16 in Groups I, II, III, IV, respectively. The postsurgical adhesions were significantly less in the groups treated with Seprafilm and Sepracoat.

The effect of medroxyprogesterone acetate and heparin in the prevention of postsurgical adhesion formation in the rat uterine model.

To evaluate the effects of depot medroxyprogesterone acetate and heparin in preventing postsurgical adhesion formation in the rat model. A hundred and five female Wistar rats were divided into 7 groups. Groups 1 and 2 were injected with intramuscular 15 mg medroxyprogesterone acetate 3 weeks before surgery and at the end of laparotomy. Groups 3 and 4 were given 15 mg medroxyprogesterone acetate by intramuscular injection, 3 weeks before surgery. An equal volume of intramuscular sterile saline was injected to control groups, 3 weeks before and at the end of surgery. Before abdominal closure, 2 ml of Ringer's lactate was instilled into the peritoneal cavity of all rats, except group 7. Groups 1, 4, and 5 were given 2 ml of intraperitoneal Ringer's lactate containing 500 U heparin/ml. A standardized surgical injury was performed in all rats. Two weeks after surgery, the adhesions were scored on a scale of 0 to 3 according to their thickness-tenacity and vascularity. Kruskall-Wallis and Mann-Whitney U statistical test were used. The preoperative and postoperative administration of medroxyprogesterone acetate resulted in the least number of and the least severe adhesions, when compared with single dose medroxyprogesterone acetate treated rats and controls (p < 0.05). However, the combination of medroxyprogesterone acetate and intraperitoneal heparin did not enhance the adhesion reducing capacity of medroxyprogesterone acetate. Concurrent preoperative and postoperative administration of medroxyprogesterone acetate results in the most significant reduction of postsurgical adhesions. The combination treatment of medroxyprogesterone acetate and heparin does not show any additional effect in the reduction of adhesion formation, when compared with medroxyprogesterone acetate treatment alone.

The comparison of gonadotropin-releasing hormone agonist therapy and intraperitoneal Ringer's lactate solution in prevention of postoperative adhesion formation in rat models

Objective: To evaluate gonadotropin-releasing hormone agonists (GnRH-a) therapy and intraperitoneal Ringer's lactate solution (RL) for the prevention of postsurgical adhesion formation in rat models. Study Design : Forty rats were randomized into four groups: Group I was the control; in group II, RL was applied at the surgery; group III and IV received preoperative subcutaneous injections of the GNRH-a leuprolide acetate and only the diluent of the GNRH-a respectively. A standard lesion was created over the uterus of each rat. Adhesions were scored at relaparotomy 3 weeks later. Analysis of variance (Kruskal–Wallis) and Mann–Whitney U-tests were used for the statistical evaluation. Results : The average adhesion scores were 2.7±0.26, 1.4±0.27, 0.9±0.18, and 2.5±0.34 in groups I, II, III, and IV respectively. There were significant differences between the scores of groups I and II ( P<0.01), groups I and III ( P<0.001), groups II and IV ( P<0.05), and groups III and IV ( P<0.01); but not between the scores of groups II and III, and groups I and IV ( P>0.05). Conclusion: GNRH-a was successful in reducing postoperative adhesion formation but was not superior to intraperitoneal RL.

Effects of Ringer’s Lactate, Medroxyprogesterone Acetate, Gonadotropin-Releasing Hormone Analogue and Its Diluent on the Prevention of Postsurgical Adhesion Formation in Rat Models

Fifty adult female rats were randomly divided into five groups. Before the standard surgical procedure which consisted of creating a lesion with electrocautery over the uterus, leuprolide acetate (LA) together with its diluent, the diluent alone and medroxyprogesterone acetate (MPA) were injected to the third, fourth, and fifth groups, respectively. Ringer’s lactate (RL) solution was applied intraperitoneally to the second group at the end of the surgery. Group I received no medication. Relaparotomy was performed 3 weeks later to evaluate the adhesions. The mean adhesion scores were (mean ± SD) 2.6 ± 0.7, 1.4 ± 0.8, 0.9 ± 0.6, 2.3 ± 0.8, and 0.8 ± 0.6 in groups I, II, III, IV, and V, respectively. The postsurgical adhesions were significantly less in the groups treated with RL, LA, and MPA.

Prevention of post-surgical adhesion formation using aspirin in a rodent model: a preliminary report.

Pelvic adhesions are one of the major factors which significantly and adversely affect surgery outcome due to intra- and postoperative morbidity and reduce future female fertility. Using a rodent model, we evaluated the efficacy of aspirin, a non-steroidal anti-inflammatory drug, in the prevention of adhesion formation. A total of 72 female Wistar rats received a standardized primary traumatic lesion to the right uterine horn. They were randomly divided into eight groups: group I (control) had no treatment and group II received a single pre-operative 0.70 mg aspirin. All the succeeding groups (III-VIII) received aspirin in doses of 0.35, 0.70, or 1.40 mg every 6 h for either 48 or 96 h in addition to the pre-operative aspirin (0.70 mg). All animals were killed 4 weeks later and adhesions were assessed using a modified adhesion scoring scale. The lowest adhesion score was found in the group treated with 0.35 mg of aspirin for 96 h, and the highest was found among the groups treated with either 0.70 or 1.40 mg for 48-96 h respectively (P < 0.05). These results are in line with the hypothesis that administration of a low dose of aspirin selectively inhibits the production of thromboxane A2, whereas basal prostacyclin biosynthesis is preserved. This phenomenon might contribute to reducing postoperative adhesion formation in a rat model. Thus, future studies into the prevention of adhesion formation may require the additional use of a non-steroidal anti-inflammatory drug, for which aspirin deserves further attention, before extrapolation into human therapy.

A pilot study of cyclosporine for the prevention of postsurgical adhesion formation in rats

OBJECTIVE: Our purpose was to evaluate the efficacy of cyclosporine in preventing primary postsurgical adhesions in the rat model. STUDY DESIGN: Thirty-two Sprague-Dawley rats underwent unilateral uterine horn injury with a combination of unipolar and bipolar cautery. Sixteen of the rats were randomized to the treatment group and received preoperative and daily cyclosporine dosing (10 mg/kg) by gavage for 14 days. At the end of the study all animals were killed, and a standard adhesion scoring system was applied by a blinded examiner. RESULTS: Adhesions were present in 75% of rats in both groups. Treatment did not affect the total adhesion score. CONCLUSION: Cyclosporine does not appear promising as a means to decrease postsurgical adhesion formation.

Localized prevention of postsurgical adhesion formation and reformation with oxidized regenerated cellulose.

We evaluated oxidized regenerated cellulose (ORC) in experimental rabbit and dog models to assess its potential for reducing or preventing adhesion formation and reformation. Evaluation was performed in the following anatomical sites: uterine horn trauma; small bowel resection and anastomosis; parietal peritoneum excision; and adhesion reformation in the uterine horn. Ten to 14 days after ORC treatment, adhesion formation was macroscopically and microscopically evaluated. Results demonstrate that ORC produced graded reduction in adhesion formation and significantly prevented adhesion reformation.