Effects of the intraperitoneal lornoxicam on the formation of intraperitoneal adhesions in rat peritonitis model

BACKGROUND: To investigate the effects of intraperitoneally administered lornoxicam on adhesion formation, bursting pressure, tissue antioxidant levels, morbidity and mortality after ileocolic anastomosis in a rat bacterial peritonitis model. METHODS: Thirty-six rats were divided into three random groups. Bacterial peritonitis was induced by performing a cecal ligation and puncture, then the cecal was resected and ileocolic anastomosis was performed. Rats of groups 1, 2 and 3 were given 2 mL normal saline, 2 mL lornoxicam, and nothing, respectively. All groups were killed at day 14. Adhesions were scored, and the presence of intra-abdominal abscesses and fistulas were noted. Anastomotic healing was assessed by bursting pressure. Tissue antioxidant levels were tested from left abdominal walls. RESULTS: One day after cecal ligation and puncture, microbiological examination showed polymicrobial bacterial peritonitis. The rats treated with lornoxicam had significantly lower adhesion scores than did the saline and nothing treated rats (P = 0.007). Bursting pressures of groups were unaffected by the treatment. Tissue antioxidant levels of groups were affected by the treatment. Morbidity and mortality were similar in all groups. CONCLUSIONS: The present study demonstrated that a single intraperitoneal instillation of lornoxicam in buffer solution at the end of the surgery reduces adhesion formation in rats bacterial peritonitis model. It was also determined that lornoxicam had no negative effect on the healing of intestinal anastomosis, abscess and anastomotic leakage. Use of lornoxicam in peritonitis was effective in decreasing the oxidative stress of tissue during peritonitis.     

Effect of intraperitoneal antiadhesive fluids in a rat peritonitis model

HYPOTHESIS: Phospholipids and icodextrin reduce peritoneal adhesions resulting from general peritonitis without promoting abscess formation. DESIGN: Evaluation of adhesion reduction fluids in a randomized animal study using a standardized peritonitis model. SETTING: Experimental animal model in a university laboratory. INTERVENTIONS: In 60 rats, experimental peritonitis was induced using the cecal ligation and puncture model. On day 1, the abdominal cavity was rinsed with 10 mL of isotonic sodium chloride solution and the cecum was resected. Animals were randomly assigned to 3 groups: the RL group, which received Ringer lactate intraperitoneally; the PL group, which received phospholipids intraperitoneally; and the ID group, which received icodextrin intraperitoneally. In each group, 50% of the animals were humanely killed at day 11 and 50% at day 21. MAIN OUTCOME MEASURES: The areas of adhesions were measured and the abscess formation was scored according to location and size. Abscesses, abdominal fluid, and blood were sampled for microbiologic workup. RESULTS: The median area of adhesions was significantly lower in the PL groups (PL(11), 43.7 mm(2); PL(21), 20.4 mm( 2)) than in the RL groups (RL(11), 163.8 mm(2); RL( 21), 120.9 mm(2)) and ID groups (ID(11), 418.5 mm( 2); ID(21), 218.6 mm(2)). Abscess formation was increased by icodextrin but not influenced by phospholipids, whereas microbiologic investigations did not reveal any differences among these 3 groups. CONCLUSIONS: In this model of general peritonitis, phospholipids significantly reduced adhesion formation without promoting septic complications. Icodextrin enhanced adhesion and abscess formation in this peritonitis model. Phospholipids may be beneficial for adhesion control in general peritonitis.     

Prevention of intraperitoneal adhesion formation using beta-glucan after ileocolic anastomosis in a rat bacterial peritonitis model

BACKGROUND: To investigate the effects of beta-glucan on intraabdominal abscess and adhesion formation after ileocolic anastomosis in a rat bacterial peritonitis model. METHODS: Sixty male Wistar rats were used in this study. Bacterial peritonitis was induced by performing a cecal ligation and puncture (CLP). On the first day, abdomen was reopened and peritoneal fluid samples were taken for microbiological examination. Thereafter, cecum was resected and ileocolic anastomosis was made. Group 1 rats were given 1 mL of normal saline as a placebo. Group 2 and group 3 rats were given beta-D-glucan 2 mg/kg by intramuscularly; 1 mg of beta-1,3-D-glucanase was administered to group 3 rats just after the use of beta-D-glucan. Half of each group were killed at day 7 and at day 21, respectively. Adhesions were scored and the presence of intraabdominal abscesses was noted. RESULTS: One day after CLP, microbiological examination showed polymicrobial bacterial peritonitis. Five (8%) of the 60 animals died owing to sepsis. One week after CLP, in two rats in each group developed abscess formation. Three weeks after CLP, abscess formation was observed in only one rat in each group. The rats treated with the beta-glucan had significantly lower adhesion scores than did the saline-treated rats (P = 0.008 at one week; P = 0.001 at 3 weeks). Administration of beta-glucanase inhibited beta-glucan activity and resulted in more adhesions (P = 0.022 at 1 week; P = 0.006 at 3 weeks). CONCLUSIONS: Although the use of beta-glucan after ileocolic anastomosis in rats with experimentally developed intraabdominal sepsis does not have any significantly effect on mortality and abscess formation, beta-glucan is capable of reducing the frequency of adhesion. This effect of beta-glucan has been prevented with beta-glucanase     

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.     

Prevention of peritoneal adhesions in the rat with sustained intraperitoneal dexamethasone delivered by a novel therapeutic system

The rat caecal crush model for the production of intraperitoneal adhesions was optimized with respect to an objective adhesion grading system based on the determination of the incidence of adhesions and the caecal adherent surface area. Intraperitoneal saline solution given before closure of the peritoneum significantly reduced the severity but not the incidence of adhesions. The addition of dexamethasone crystal suspension led to somewhat lower incidence of adhesions but the mean adherent surface area values were not different from the saline regimen. However, sustained release of dexamethasone by use of intraperitoneal biodegradable poly(lactide-co-glycolide) microparticles as a novel therapeutic system further reduced both the incidence and the severity of adhesions. Despite of the differences in therapeutic effects glucocorticoid-associated local and systemic adverse effects were similar in both regimens. As effective adhesion prophylaxis with glucocorticoids appears to be a balance between benefit and adverse reactions, optimal drug delivery is mandatory. The novel biodegradable therapeutic system is superior to the intraperitoneal crystal suspension regimen in the rat and should be tested further in clinical trials.     

Polyanionic polysaccharides reduce intra-abdominal adhesion and abscess formation in a rat peritonitis model.

BACKGROUND: Intra-abdominal infection is complicated by adhesion and abscess formation. We have assessed the adhesion- and abscess-reducing capacity of various solution volumes and concentrations of two polyanionic polysaccharides, hyaluronan (HA) and carboxymethylcellulose (CMC), in a rat peritonitis model. STUDY DESIGN: In 192 male Wistar rats a bacterial peritonitis was induced using cecal ligation and puncture. After 24 h the abdomen was reopened and the ligated cecum resected. Animals were randomized into three control groups, nine groups treated with various solution volumes (1 to 8 ml) containing different HA concentrations, and four groups treated with 1.7% CMC solution. Rats were killed at day 7, postoperatively, and adhesions were scored at five abdominal sites on a scale from 0 to 4. The presence and size of intra-abdominal abscesses were noted. RESULTS: Fifty-four rats (28%) prematurely died. There was no significant difference in mortality between treatment groups and controls. Treatment with CMC (P < 0.001) and low (0.2 and 0.4%) concentrations of HA (P < 0.005) significantly reduced intra-abdominal adhesion formation. High volumes of 0.2 and 0.4% HA were most effective (P = 0.01). The effect of CMC was volume independent. The incidence of abdominal abscesses was also significantly reduced by treatment with either CMC (P < 0.001) or low concentrations of HA (P < 0.001). With regard to abscess formation the effect was independent of the volume administered for HA, while low volumes of CMC were most effective (P < 0.005). CONCLUSION: Intraperitoneal treatment with either CMC or low-viscosity HA solution reduced intra-abdominal adhesion and abscess formation in a rat peritonitis model. The volume-induced reduction in adhesion formation suggests a hydroflotation effect of HA solution.     

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.     

Characterizing omental adhesions by culturing cells isolated from a novel in vivo adhesion model

Although it has been established that postoperative adhesions in the peritoneal cavity are the consequence of injury to the peritoneum, there is much controversy over the nature of the cells giving rise to this neotissue. Here, we establish a novel adhesiogenic model in the rabbit to analyze the phenotype and proliferation in vitro of cells comprising adhesion tissue seven days postsurgery. Adhesion-free omentum tissue was used as control. Cells derived from adhesions and from the control omentum were subcultured and characterized through immunofluorescence and Western blotting procedures to determine markers of cell differentiation and pluripotential, and viability and proliferation assays. Our findings indicate the existence of a mesenchymal population in the omentum revealed by markers of pluripotent cells with high angiogenic capacity. This population seems to be responsible for the adhesions formed in response to mesothelial damage. Depending on the local environment, mesenchymal cells are capable of in vivo differentiation towards at least two different cell phenotypes rendering two types of adhesions with clearly differentiated characteristics. One type of adhesion shows a highly vascularized adipose morphology containing cells differentiating into a vascular lineage. The other adhesions are fibrous with large amounts of collagen and comprised mainly of myofibroblasts conferring less compliance to this tissue.     

Auto-cross-linked hyaluronic acid gel does not reduce intra-abdominal adhesions or abscess formation in a rat model of peritonitis

BACKGROUND: Prevention of adhesion and abscess formation would decrease mortality and morbidity after peritonitis. In this study the effect of a new anti-adhesive, auto-cross-linked hyaluronic acid polysaccharide (ACP) gel, on adhesion and abscess formation was studied in a rat peritonitis model. MATERIALS AND METHODS: In experiment 1, bacterial peritonitis was induced in 24 Wistar rats, using a cecal ligation and puncture model. Animals were randomized to receive 4 mL ACP gel (4%) or 4 mL phosphate buffered saline (PBS). After 2 weeks animals were killed and adhesions and abscesses were scored. In experiment 2, 72 rats underwent the same procedure but were randomized to receive 2 mL ACP gel, 4 mL ACP gel, or 4 mL PBS. After 1 and 3 weeks, respectively, half of the animals in each group were killed and adhesions and abscesses were scored. RESULTS: The median total adhesion score was 12 (range, 3-20) in the ACP group and was 9 (range, 6-12) in the PBS group (not significant) in experiment 1. 91% of rats in the ACP group developed abscesses, versus 90% in the control group. There were no significant differences in abscess size or number of abscesses. In experiment 2, total adhesion scores in the 2 mL ACP group, 4 mL ACP group, and PBS group were 4 (range, 2-20), 6 (range, 1-11), and 6 (range, 1-18), respectively, (not significant) after 1 week and 3.5 (range, 1-8), 5 (range, 2-15), and 4 (range, 0-9), respectively, (not significant) after 3 weeks. All rats in the 2 mL ACP group and the PBS group and 83% of the 4 mL ACP group had developed abscesses after 1 week. After 3 weeks these percentages were 80, 75, and 73, respectively. There were no significant differences in size or number of abscesses between groups both after 1 and 3 weeks. CONCLUSION: ACP does not reduce adhesion and abscess formation in a rat peritonitis model.     

Sepramesh and postoperative peritoneal adhesions in a rat model

Purpose: The present study aimed to investigate the safety and the anti-postoperative peritoneal adhesion (PPA) characteristics of Sepramesh^® (Davol), a composite mesh made of polypropylene covered with Seprafilm, when intraperitoneally placed in a rat model.

Methods: Twenty male rats were randomized into a control group and a Sepramesh group. They underwent a primary surgical procedure aiming to induce a peritoneal injury in order to induce PPAs. In the Sepramesh group, the burnt peritoneum was covered with a 2-cm diameter disc of Sepramesh prosthesis. The mesh was fixed to the parietal peritoneum with four 3-0 absorbable stitches. PPAs were assessed during a second laparotomy 10 days later using quantitative and qualitative scoring systems.

Results: There was no difference in terms of mean number of PPAs between both groups. All the rats from the control group developed PPAs. In the Sepramesh group, no adhesions were observed at the site of the injured peritoneum that had been covered with the Sepramesh prosthesis, but PPAs occurred at the extremities of the mesh, where there was close contact between polypropylene and viscera, or where the fixation sutures were placed. The severity and the type of adhesions were significantly higher in the control group.

Conclusions: This study demonstrated that for the Sepramesh prostheses, the Seprafilm layer might be effective in PPA prevention, but damage caused by the section and fixation of Sepramesh should be limited in order to limit PPAs.     

Prevention of adhesions to polypropylene mesh in a rabbit model

The purpose of this study was to develop a quantitative model for evaluating adhesion formation and to determine whether Seprafilm (HAL-F) bioresorbable membrane (Genzyme Corp., Cambridge, MA) is effective in preventing adhesions to polypropylene mesh (PPM). PPM has been shown to be an effective material for the repair of abdominal wall defects. One disadvantage of PPM is its tendency to form dense adhesions when in contact with abdominal viscera. HAL-F, a sodium hyaluronate/carboxymethylcellulose absorbable membrane, has been shown to prevent adhesion formation after midline closures. Its efficacy in preventing adhesions to PPM has not been examined previously. A 5 x 7-cm anterior abdominal wall defect was created in 24 New Zealand White rabbits. This defect was then repaired with PPM. In the experimental group, a 5 x 7-cm piece of HAL-F was placed between the mesh and the abdominal viscera. At 30 days, the animals were killed and adhesions were categorized and quantified using digital image analysis of inked specimens. The strength of mesh incorporation into surrounding tissues was also examined using an Instron tensiometer. The formation of adhesions between the viscera and mesh repair was significantly reduced by the use of HAL-F. The surface area involved for bowel adhesions was reduced 94 per cent (P = 0.00132). The strength of incorporation was not adversely affected. HAL-F is highly effective in preventing adhesions to PPM, without adversely effecting the strength of mesh incorporation.     

Prevention of intraperitoneal adhesions: a comparison of noxythiolin and a new povidone-iodine/PVP solution.

Peritoneal adhesions were induced in 250 female Wistar rats by the excision and closure of a right lower quadrant parietal peritoneal defect. After closure of the defect each rat was randomly allocated to one of five treatment groups: A, control with no instillate; B, control with Ringer solution; C, noxythiolin 0.5 per cent solution; D, noxythiolin 1 per cent solution; E povidone-iodine/PVP solution. Two millilitres of the appropriate solution were injected into the peritoneal cavity just before closure of a standard 4-cm midline incision. Assessment of adhesion formation was made at 1 week in ignorance of the treatment group. Noxythiolin 1 per cent was more effective than Ringer solution and noxythiolin 0.5 per cent in reducing the mean number of adhesions (P less than 0.05) but was inferior to povidone-iodine/PVP (P less than 0.05). Povidone-iodine/PVP solution significantly reduced the number of adhesions compared with the four other groups. In addition, it significantly reduced the mean length of attachment of each adhesion compared with the two control groups (P less than 0.001).     

Prevention of adhesions to polypropylene mesh in a traumatized bowel model

BACKGROUND: Polypropylene mesh (PPM) is an effective material for the repair of abdominal wall defects, but has a tendency to induce dense adhesions when in contact with viscera. Seprafilm (Genzyme Corp, Cambridge, MA), a bioresorbable membrane, has been shown to reduce adhesion formation after midline closures in humans and to PPM in animals. Given the increased inflammatory response expected with surgical trauma, its efficacy under surgical conditions has been questioned. STUDY DESIGN: A prospective, randomized, blinded study was conducted using a rabbit model. Standardized abdominal wall defects were created in three groups of New Zealand white rabbits. The cecum was deserosalized to simulate the effects of trauma. The abdominal defect was then repaired with PPM. In the control group, no Seprafilm was used. In the first experimental group Seprafilm was placed between the mesh and the abdominal viscera. In the second experimental group Seprafilm was placed over the deserosalized area and between the mesh and abdominal viscera. Animals were sacrificed at 30 days and adhesions were categorized and quantified using digital image analysis of inked specimens. The strength of incorporation was also determined. RESULTS: The formation of adhesions between the viscera and mesh repair was dramatically reduced in both experimental groups compared with the control group. The incidence of visceral adhesions was reduced by 80% in the single film group (p = 0.0004) and 90% in the double film group (p = 0.00008). The reduction in surface area of adhesions was 96.4% in the single film group (p = 0.000019) and 99.4% in the double film group (p = 0.00002). Omental adhesions were reduced by 30% but this did not achieve statistical significance. Strength of incorporation was not adversely affected in either group. CONCLUSIONS: Seprafilm is highly effective in preventing adhesions to PPM. This effect was not diminished by the presence of visceral trauma and its resultant inflammatory response. The use of Seprafilm does not adversely affect tissue incorporation. Clinical trials are warranted to determine if the protective effects of Seprafilm demonstrated in this study are applicable in the clinical setting.     

Prevention of peritoneal carcinomatosis from human gastric cancer cells by adjuvant-type intraperitoneal immunotherapy in a SCID mouse model

PURPOSE: We analyzed the effect of intraperitoneal immunotherapy in an animal model mimicking locoregional dissemination of tumor cells during resection of advanced tumors. METHODS: We first established a tumor model with human gastric cancer cells (MKN-45) in the peritoneal cavity of CB-17-SCID mice. Three hours following the injection of tumor cells into the peritoneal cavity, mAb 17-1A alone and in combination with human LAK cells were given intraperitoneally at different dosages. The results were quantified by determining the weight of the peritoneal tumor masses. RESULTS: After intraperitoneal administration of 17-1A mAb, a tumor reduction could be shown (median tumor mass after 10 microg mAb: 171 microg; after 100 microg: 130 microg) when compared with the control group (632 microg). Following a combined therapy with mAb and LAK cells, a statistically significant tumor reduction could be observed (after 10 microg mAb + 20-50 x 10(6) LAK cells: 80 microg; after 100 microg mAb + 20-50 x 10(6) LAK cells: 12 microg, p = 0.0005). With specific dosages of antibody and LAK cells it was even possible to achieve complete tumor clearance. CONCLUSIONS: Intraperitoneal immunotherapy reduces the peritoneal tumor masses and can even prevent the peritoneal carcinomatosis formation.     

The impact of conventional and laparoscopic colon resection (CO2 or helium) on intraperitoneal adhesion formation in a rat peritonitis model

apd: 6 February 2001