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A Novel Method for Evaluating Postoperative Adhesions in Rats
Journal of Investigative Surgery
Abstract
Materials and methods:
A model of cecal abrasion with partial sidewall attachment was performed on female rats. After 1, 2, 4, or 7 days of recovery, the rats were euthanized and their abdominopelvic cavities were systematically evaluated for postoperative adhesions. The necropsy was recorded through the surgical microscope. Four raters were trained to use a ballot to capture key factors of the adhesions as they viewed the recordings. Their ratings were compared for measurement error and reliability (using Bland-Altman plots and intraclass correlation coefficients, respectively) and for the ability to discriminate differences in experimental groups. A subset of the data was analyzed to determine practical utility.
Results:
The rating system was shown to have low measurement error and high inter-rater reliability for all parameters measured. Applied practically, the system was able to discriminate groups in a manner that was expected.
Conclusions:
We have developed and validated a rating system for postoperative adhesions and shown that it can detect group differences. This method can be used to quantify postoperative adhesions in rodent models.
... The cecum was retrieved and two 4-0 nylon sutures were placed attaching the greater curvature to the abdominal wall, 1-2 mm cranial and caudal to the centerline of the abdominal wall lesion, with no tension between the sutures (Fig 1A). Because the cecum was free to move along an axis between the sutures, we termed this the "cecal hinge" model [29]. We termed the resultant adhesion development at this location the "primary adhesion." ...
... Intraperitoneal adhesion rating. The severities of the intraperitoneal adhesions (not including the primary adhesions) were rated using a consensus approach that we have recently described [29]. Four investigators familiar with the methods but not otherwise involved in the experiments performed the ratings. ...
... Therefore, to analyze the proportions of rats with or without adhesions, we defined total areas of less than 20 mm 2 as "no adhesion," and performed a Fisher's Exact test for proportions (two-tailed). The video ratings were analyzed as previously described [29]. Rating data, fecal pellet counts, and macrophage data were analyzed using 2-way ANOVA corrected for multiple comparisons using Sidak post hoc tests. ...
Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. We hypothesized that postoperative adhesions develop from a lack of movement of the abdominopelvic organs in the immediate postoperative period while rendered immobile by surgery and opiates, and tested whether manual therapy would prevent their development. In a modified rat cecal abrasion model, rats were allocated to receive treatment with manual therapy or not, and their resulting adhesions were quantified. We also characterized macrophage phenotype. In separate experiments we tested the safety of the treatment on a strictureplasty model, and also the efficacy of the treatment following adhesiolysis. We show that the treatment led to reduced frequency and size of cohesive adhesions, but not other types of adhesions, such as those involving intraperitoneal fatty structures. This effect was associated with a delay in the appearance of trophic macrophages. The treatment did not inhibit healing or induce undesirable complications following strictureplasty. Our results support that that maintained movements of damaged structures in the immediate postoperative period has potential to act as an effective preventive for attenuating cohesive postoperative adhesion development. Our findings lay the groundwork for further research, including mechanical and pharmacologic approaches to maintain movements during healing.
... From the descriptions in the mAFS scoring system, it is easily seen that it is more suitable for CSM rather than IBM, which indicates that it is also important to choose a proper scoring system to match the model used. In addition, when using a scoring system, Geoffrey et al. reported that the evaluation is more reliable when scored by one trained rater with a scoring system that is divided into several specific indicators [239] . ...
Peritoneal adhesions (PA) are a postoperative syndrome with high incidence rate, which can cause chronic abdominal pain, intestinal obstruction, and female infertility. Previous studies have identified that PA are caused by a disordered feedback of blood coagulation, inflammation, and fibrinolysis. Monocytes, macrophages, fibroblasts, and mesothelial cells are involved in this process, and secreted signaling molecules, such as tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), tissue plasminogen activator (tPA), and type 1 plasminogen activator inhibitor (PAI-1), play a key role in PA development. There have been many attempts to prevent PA formation by anti-PA drugs, barriers, and other therapeutic methods, but their effectiveness has not been widely accepted. Treatment by biomaterial-based barriers is believed to be the most promising method to prevent PA formation in recent years. In this review, the pathogenesis, treatment approaches, and animal models of PA are summarized and discussed to understand the challenges faced in the biomaterial-based anti-PA treatments.
Background
Abdominal adhesions are the most common surgical complication and without reliable prophylactics. This study presents a novel rat model for abdominal adhesions and reports pilot results of human placental stem cell (hPSC)‐based therapies.
Methods
Forty‐four ( n = 44) male Sprague–Dawley rats (250‐350 g) were used in the experiment. Of these, thirty‐eight ( n = 38) were included in a preliminary data set to determine a minimum treatment effect. Adhesions were created in a reproducible model to the abdominal wall and between organs. Experimental groups included the control group (Model No Treatment, MNT), Plasmalyte A (Media Alone, MA, 10 mL), hPSC (5 × 10 ⁶ cells/10 mL Plasmalyte A), hPSC‐CM (hPSC secretome, conditioned media) in 10 mL Plasmalyte A, Seprafilm™ (Baxter, Deerfield, IL), and sham animals (laparotomy only). Treatments were inserted intraperitoneally (IP) and the study period was 14 days post‐operation. Results are reported as the difference between means of an index statistic (AIS, Animal Index Score) and compared by ANOVA with pairwise comparison.
Results
The overall mean AIS was 23 (SD 6.16) for the MNT group with an average of 75% of ischemic buttons involved in abdominal adhesions. Treatment groups MA (mean overall AIS 17.33 SD 6.4), hPSC (mean overall AIS 13.86 SD 5.01), hPSC‐CM (mean overall AIS 13.13 SD 6.15), and Seprafilm (mean overall AIS 13.43 SD 9.11) generated effect sizes of 5.67, 9.14, 9.87, and 9.57 decrease in mean overall AIS, respectively, versus the MNT.
Discussion
The presented rat model and scoring system represent the clinical adhesion disease process. hPSC‐based interventions significantly reduce abdominal adhesions in this pilot dataset.
The use of interrater reliability (IRR) and interrater agreement (IRA) indices has increased dramatically during the past 20 years. This popularity is, at least in part, because of the increased role of multilevel modeling techniques (e.g., hierarchical linear modeling and multilevel structural equation modeling) in organizational research. IRR and IRA indices are often used to justify aggregating lower-level data used in composition models. The purpose of the current article is to expose researchers to the various issues surrounding the use of IRR and IRA indices often used in conjunction with multilevel models. To achieve this goal, the authors adopt a question-and-answer format and provide a tutorial in the appendices illustrating how these indices may be computed using the SPSS software.
Peritoneal adhesions following surgery are a common, serious pathology with severe complications. Appropriate animal adhesion models are essential for the assessment of adhesion preventing medical devices. This study introduces a variation of an established rat model in which highest degree adhesions are induced with excellent reproducibility (OPAM = optimized peritoneal adhesion model). Thus, this model seems to be eligible to study effects of adhesion preventing devices.
24 Lewis male rats were divided into four groups (OPAM, WSFX, sham-OPAM, sham-WSFX). The OPAM technique comprised cecal abrasion, creation of an abdominal wall defect plus approximation of injured areas by a suture, which was compared to a setting of lesions without suture fixation (WSFX). All rats were sacrificed at day 7. Macroscopic and histopathological evaluations were performed. RESULTS were statistically analyzed using ANOVA and Dunnett's test.
In OPAM rats macroscopic analyses revealed a 90% incidence adhesion of cecum to the abdominal wall, all adhesions imposing as complete agglutination. In WSFX animals incidence of adhesions formation was 75%, while in both sham groups there were no adhesions at all. Histology showed the structure of adhesions with merged smooth muscle of colon and skeletal muscle of abdominal wall in all cases.
OPAM technique provides adhesions of injured areas with a better probability than with conventional methods. All OPAM adhesions impressed as highest degree adhesions, i.e. agglutination. Due to high reproducibility in incidence and extend of adhesion formation, the OPAM is recommended for testing of adhesion prevention medical devices.
The use of interrater reliability (IRR) and interrater agreement (IRA) indices has increased dramatically during the past 20 years. This popularity is, at least in part, because of the increased role of multilevel modeling techniques (e.g., hierarchical linear modeling and multilevel structural equation modeling) in organizational research. IRR and IRA indices are often used to justify aggregating lower-level data used in composition models. The purpose of the current article is to expose researchers to the various issues surrounding the use of IRR and IRA indices often used in conjunction with multilevel models. To achieve this goal, the authors adopt a question-and-answer format and provide a tutorial in the appendices illustrating how these indices may be computed using the SPSS software.
Reliability coefficients often take the form of intraclass correlation coefficients. In this article, guidelines are given for choosing among 6 different forms of the intraclass correlation for reliability studies in which n targets are rated by k judges. Relevant to the choice of the coefficient are the appropriate statistical model for the reliability study and the applications to be made of the reliability results. Confidence intervals for each of the forms are reviewed. (23 ref) (PsycINFO Database Record (c) 2006 APA, all rights reserved).
Infertility and intestinal obstruction are well-known complications, arising from adhesion formation after intra-abdominal operations. Basic principles of adhesion formation have been found through animal studies. In addition, examination of agents for the prevention of adhesions can be easily made using experimental studies. However, lack of uniformity in study design makes assessment of the efficacy of any prophylactic regimen difficult. In this review, the material and methods used in experimental studies designed for adhesion formation or prevention were evaluated in detail, with experimental studies published in the literature from 1960 to 2003 being evaluated. Several methods for adhesion induction have been described in the literature. Severity of the adhesion varies from method to method, with the main problem being the lack of uniform expression of study results. Extensive use of complex adhesion classification systems should be used to resolve this discordance between experimental studies.
Objective:
To provide a comprehensive review of recent epidemiologic data on the burden of adhesion-related complications and adhesion prevention. Second, we elaborate on economic considerations for the application of antiadhesion barriers.
Background:
Because the landmark SCAR studies elucidated the impact of adhesions on readmissions for long-term complications of abdominal surgery, adhesions are widely recognized as one of the most common causes for complications after abdominal surgery. Concurrently, interest in adhesion prevention revived and several new antiadhesion barriers were developed. Although these barriers have now been around for more than a decade, adhesion prevention is still seldom applied.
Methods:
The first part of this article is a narrative review evaluating the results of recent epidemiological studies on adhesion-related complications and adhesion prevention. In part II, these epidemiological data are translated into a cost model of adhesion-related complications and the potential cost-effectiveness of antiadhesion barriers is explored.
Results:
New epidemiologic data warrant a shift in our understanding of the socioeconomic burden of adhesion-related complications and the indications for adhesion prevention strategies. Increasing evidence from cohort studies and systematic reviews shows that difficulties during reoperations, rather than small bowel obstructions, account for the majority of adhesion-related morbidity. Laparoscopy and antiadhesion barriers have proven to reduce adhesion formation and related morbidity. The direct health care costs associated with treatment of adhesion-related complications within the first 5 years after surgery are 970 after laparoscopy. Costs are about 50% higher in fertile-aged female patients. Application of an antiadhesion barriers could save between 680 after open surgery. After laparoscopy, the costs impact ranges from 63 of savings.
Conclusions:
Adhesions are an important cause for long-term complications in both open and laparoscopic surgery. Adhesiolysis during reoperations seems to impact adhesion-related morbidity most. Routine application of antiadhesion barriers in open surgery is safe and cost-effective. Application of antiadhesion barriers can be cost-effective in selected cases of laparoscopy. More research is needed to develop barriers suitable for laparoscopic use.
THE FECTIVENESS of intraperitoneal injection of povidone (Plasdone C) in prevention of reformation of peritoneal adhesions is presented in our preliminary report in 1964.¹ The excellent result in reduction of adhesions in two groups of rabbits from 75% to 88% in extent and 57% to 71% in density¹ was in favor of further investigation. It was suggested that procedure is practical and has two advantages: simplicity and transient presence of the introduced ascites.
The prophylactic result in formation of adhesions which is presented by Choate et al² using dextran in rats, was initiative for investigation of the effect of dextran and comparison with povidone in prevention of reformation of peritoneal adhesions. There are few reports1,3-5 in the literature in favor of our study. The results are indicative that further exploration of the subject is worthwhile and may contribute a solution for an unsolved problem in surgery.
Formation of adhesions after peritoneal surgery results in high morbidity. Barriers to prevent adhesion are seldom applied, despite their ability to reduce the severity of adhesion formation. We evaluated the benefits and harms of four adhesion barriers that have been approved for clinical use.
In this systematic review and meta-analysis, we searched PubMed, CENTRAL, and Embase for randomised clinical trials assessing use of oxidised regenerated cellulose, hyaluronate carboxymethylcellulose, icodextrin, or polyethylene glycol in abdominal surgery. Two researchers independently identified reports and extracted data. We compared use of a barrier with no barrier for nine predefined outcomes, graded for clinical relevance. The primary outcome was reoperation for adhesive small bowel obstruction. We assessed systematic error, random error, and design error with the error matrix approach. This study is registered with PROSPERO, number CRD42012003321.
Our search returned 1840 results, from which 28 trials (5191 patients) were included in our meta-analysis. The risks of systematic and random errors were low. No trials reported data for the effect of oxidised regenerated cellulose or polyethylene glycol on reoperations for adhesive small bowel obstruction. Oxidised regenerated cellulose reduced the incidence of adhesions (relative risk [RR] 0·51, 95% CI 0·31-0·86). Some evidence suggests that hyaluronate carboxymethylcellulose reduces the incidence of reoperations for adhesive small bowel obstruction (RR 0·49, 95% CI 0·28-0·88). For icodextrin, reoperation for adhesive small bowel obstruction did not differ significantly between groups (RR 0·33, 95% CI 0·03-3·11). No barriers were associated with an increase in serious adverse events.
Oxidised regenerated cellulose and hyaluronate carboxymethylcellulose can safely reduce clinically relevant consequences of adhesions.
None.
Background:
Intraabdominal peritoneal adhesions are a significant cause of postoperative morbidity and remain one of the major long-term complications associated with abdominal surgery. Adhesion formation at the molecular level involves a complex interaction of cytokines, growth factors, cell adhesion molecules, and neuropeptides, as well as many other factors secreted by cells proximate to the traumatized area. Limited studies exist which investigate the molecular processes involved in adhesion formation. Therefore, the aim of the present study was to determine the pattern of gene expression for substance P, the neurokinin-1 receptor, and downstream mediators of substance P action during the early stages of adhesion formation in the rat.
Methods:
Four ischemic buttons were created on one side of the peritoneum in male Wistar rats. Animals were sacrificed at 3, 6, and 12 h and 1, 3, 5, and 7 days following surgery. Peritoneal tissue from ischemic buttons and from the opposite sidewall was harvested for total RNA isolation. Semiquantitative RT-PCR was used to measure changes at the transcript level for the neurokinin-1 receptor, substance P, TGFbeta-1, and the cell adhesion molecules ICAM-1 and VCAM-1.
Results:
Messenger RNA levels for substance P, neurokinin-1 receptor, TGFbeta-1, ICAM-1, and VCAM-1 were significantly increased in peritoneal tissue taken from ischemic button sites (P < 0.05) when compared with controls. In the peritoneal tissues taken from the opposite sidewall, there was a significant (P < 0.05) early increase in substance P mRNA levels. TGF-beta1, neurokinin-1 receptor, and ICAM-1 mRNA levels were also significantly (P < 0.05) increased when compared to controls, while the mRNA levels for VCAM-1 did not change.
Conclusions:
The increased levels of mRNA for substance P, the neurokinin-1 receptor, and the downstream mediators of substance P action, TGF-beta1, ICAM-1, and VCAM-1, in peritoneal tissue associated with intraabdominal adhesions support a role for substance P in adhesion formation.
Peritoneal adhesions are almost ubiquitous following surgery. Peritoneal adhesions can lead to bowel obstruction, digestive problems, infertility, and pain, resulting in many hospital readmissions. Many approaches have been used to prevent or treat adhesions, but none offer reliable results. A method that consistently prevented or treated adhesions would benefit many patients. We hypothesized that an anatomically-based visceral mobilization, designed to promote normal mobility of the abdominal contents, could manually lyse and prevent surgically-induced adhesions.
Cecal and abdominal wall abrasion was used to induce adhesions in 3 groups of 10 rats (Control, Lysis, and Preventive). All rats were evaluated 7 days following surgery. On postoperative day 7, unsedated rats in the Lysis group were treated using visceral mobilization, consisting of digital palpation, efforts to manually lyse restrictions, and mobilization of their abdominal walls and viscera. This was followed by immediate post-mortem adhesion evaluation. The rats in the Preventive group were treated daily in a similar fashion, starting the day after surgery. Adhesions in the Control rats were evaluated 7 days after surgery without any visceral mobilization.
The therapist could palpate adhesions between the cecum and other viscera or the abdominal wall. Adhesion severity and number of adhesions were significantly lower in the Preventive group compared to other groups. In the Lysis and Preventive groups there were clear signs of disrupted adhesions.
These initial observations support visceral mobilization may have a role in the prevention and treatment of post-operative adhesions.
To explore recent developments in the techniques used for the prevention of adhesion formation after gynaecological surgery as well as the current evidence for existing agents and techniques.
Recent developments are promising new biomaterials such as polyvinyl alcohol gel and hyaluronic acid cross-linked with various agents such as nanoparticles. Other substances that have recently received attention include novel anti-inflammatory agents, Oxiplex (FzioMed, Inc., San Luis Obispo, California, USA), sildenafil, statins and also, there has been some renewed interest in dextran. Furthermore, the combination of barrier and pharmacological agents has led to the introduction of interesting new hybrid systems. Finally, despite the development of many novel antiadhesion agents, good surgical technique remains the mainstay of adhesion prevention.
There is preliminary evidence to support the use of hyaluronic acid, although the best preparation is yet to be determined. The use of icodextrin, Interceed (Ethicon Inc, Somerville, New Jersey, USA) and Oxiplex seem to be justified by the currently available data. The results of interesting new technologies such as the use of hybrid systems and new forms of biomaterials are awaited.
In clinical measurement comparison of a new measurement technique with an established one is often needed to see whether they agree sufficiently for the new to replace the old. Such investigations are often analysed inappropriately, notably by using correlation coefficients. The use of correlation is misleading. An alternative approach, based on graphical techniques and simple calculations, is described, together with the relation between this analysis and the assessment of repeatability.
Adhesion-related complications after abdominal surgery result in significant morbidity and costs. Results from animal studies investigating prevention or treatment of adhesions are limited due to lack of consistency in existing animal models. The aim of this study was to compare quality and quantity of adhesions in four different models and to find the best model.
This study was approved by the University of Missouri Animal Care and Use Committee (ACUC). Forty female rats were randomly assigned to four different groups of 10 animals each. Adhesion created was performed utilizing the four techniques: Group 1 - parietal peritoneum excision (PPE), Group 2 - parietal peritoneum abrasion (PPA), Group 3 - peritoneal button creation (PBC), and Group 4 - cecal abrasion (CA). Rats were allowed to recover and necropsy was performed on postoperative d 14. Adhesions were scored by an established quantitative and qualitative scoring systems. The midline incision served as the control in each animal.
The four groups were not equal with respect to both quantity score (P<0.001) and quality score (P=0.042). The PBC group had the highest quantity of adhesions. The highest quality of adhesion was seen in the PPE group. A multivariate analysis carried out to quantify the performance of each model clearly demonstrated that PBC exhibited the best results in terms of both quantity and quality.
The button technique (PBC) is most consistent and reproducible technique for an intra-abdominal adhesion model. This model can help in the study and development of substances to prevent adhesion formation in the future.
The immunosuppressive and anti-inflammatory properties of progesterone (P) have been established. The authors investigated whether the intraperitoneal instillation of P would lessen postoperative adhesion formation in New Zealand white rabbits undergoing pelvic surgical procedures. In phase I, severe, peritoneal lesions were made in the right uterine horn (n = 48). Animals were randomized to receive equal volumes of either (1) Ringer's lactate (RL); (2) 32% dextran 70 (HY; Hyskon Division, Pharmacia, Piscataway, NJ); (3) 500 mg P in oil (PO); or (4) 500 mg aqueous P (PA) at initial laparotomy. In phase II, the distal right uterine horn, including the mesosalpinx, was excised and microsurgical anastomosis was accomplished (n = 45). Aqueous P was not used in phase II; otherwise, the same agents were tested. Six weeks later, the severity of the adhesions formed was graded. The mean adhesion scores for the RL and HY groups were low for the right side in both phases and did not differ (P greater than 0.05). In contrast, higher scores were observed in all the P groups, regardless of the P preparation used or the surgical procedure performed (P less than 0.05).
Despite use of surgical adjuvants, pelvic adhesions frequently develop following infertility surgery. Recently a resorbable biocompatible material, TC 7, has been designed to be used as a barrier to reduce adhesion formation. Reproducibly severe sidewall adhesions were only able to be created in one of six models tested. The model consisted of the following steps: excision of a full thickness 2 x 2-cm musculoperitoneal tissue mass, scraping of an adjacent 2-cm length of uterine horn, tamponading of all bleeding, and suturing (6-0 Vicryl) of normal tube and sidewall so as to directly approximate the traumatized tissues. Studies were conducted in 13 rabbits after creation of the bilateral sidewall and horn lesions, each serving as its own control. Choice of control and TC 7 sides was determined randomly. Adhesion formation was examined 2 weeks postoperatively. No residual material was noted at that time. Adhesion scores were the composite total of extent (0-4), type (0-4), and tenacity (0-3) of sidewall adhesions, and were significantly reduced on the TC 7 side as compared with the control side (mean 6.8 +/- 0.4 vs 9.0 +/- 0.3, median 6 vs 9, sign test P = 0.0032). No complications of use of the barrier were noted. It is concluded that use of TC 7, a resorbable biocompatible barrier, was able to significantly reduce postoperative adhesion formation on the rabbit sidewall.
To determine, in a rabbit model, whether peritoneal exposure to dermoid cyst material produces inflammation and adhesions above control levels and whether saline lavage reduces the degree of peritoneal reaction.
A prospective, randomized, blinded, controlled study of adhesion formation. Thirty New Zealand white female rabbits were assigned randomly to five experimental groups: [1] laparoscopy with intraperitoneal injection of human dermoid material, [2] laparoscopy with intraperitoneal injection of human dermoid material and subsequent lavage to clear all visible dermoid material, [3] laparoscopy with saline lavage, [4] laparoscopy with intraperitoneal injection of human follicular fluid (antigenic control), and [5] laparoscopy alone.
Six weeks after initial laparoscopy, inflammation and adhesions were scored in several categories via visual assessment (range 0 to 15) and histologic microscopic evaluation (range 0 to 24). Data were evaluated using Kruskal-Wallis and Mann-Whitney U nonparametric tests.
For groups 1, 2, 3, 4, and 5, respectively, mean +/- SEM total inflammation-adhesion scores were 13.85 +/- 0.55, 2.90 +/- 1.15, 0 +/- 0, 1.50 +/- 1.00, and 0 +/- 0 for clinical evaluation and 16.83 +/- 1.22, 7.33 +/- 1.76, 0 +/- 0,0 +/- 0, and 0 +/- 0 for histologic evaluation. Using nonparametric tests, significant differences were found between groups in clinical and histologic scores.
Dermoid material produces a significant peritonitis. Results of the clinical evaluation demonstrate that saline lavage brings inflammation and adhesion formation close to control levels. However, results of the histologic evaluation suggest that the decrement in inflammation as a result of lavage may be less dramatic than that found by clinical evaluation.
To investigate whether intraperitoneal gallstones increase the risk of pelvic adhesions in a rabbit model.
Prospective, randomized, blinded, sham and human antigen controlled trial.
An academic research environment.
Twelve New Zealand white rabbits.
Twelve rabbits were divided into three groups of four each; a sham operation group, a gallstone and bile group (study group), and a human serum albumin and bile group (antigenic control). Three weeks after the operation individual subjects were randomized, with groups concealed to observers, and a necropsy was performed on each rabbit.
Necropsy was performed on each rabbit, and the adhesions were scored for extent, type, tenacity, inflammation, and gallstone involvement.
There was a statistically and biologically significant increase in gallstone involvement in adhesions, especially pelvic adhesions, in the study group.
This study, along with an increasing number of case reports, suggests that gallstones inadvertently left in the peritoneal cavity may increase the morbidity of laparoscopic cholecystectomy. In females of reproductive age these gallstones may induce pelvic adhesions that may interfere with fertility or be associated with pelvic pain.
The purpose of this work was to investigate the local application of camptothecin (CPT), a drug with anti-inflammatory, antiproliferative and antiangiogenic properties, as an inhibitor of surgical adhesion formation in rats.
The anti-adhesion properties of CPT were investigated using the cecal sidewall abrasion model in a total of 92 rats. An adhesion score for each animal was obtained based on the strength and extent of the adhesions. Significance was determined by Students t-test and p values less than 0.05 were considered significant.
The drug was administered by application of carbodiimide crosslinked hyaluronic acid (HA) films containing CPT at concentrations of 0, 0.6, 2.5 and 7.5% w/w at the site of surgical injury. The HA films were characterized by in vitro measurements of drug release rates.
In this model the application of HA films alone, or 0, 0.6, 2.5 or 7.5% w/w CPT-loaded HA films, had a significant effect in reducing the mean strength and area of adhesions (3.8 +/- 2.7, 5.6 +/- 0.7, 1.3 +/- 0.7, 0.9 +/- 0.8, 0.7 +/- 1.0, respectively) when compared to those animals in which no film was placed (8.4 +/- 2.5). In addition, a significant difference was observed in the effect of 0.6, 2.5 and 7.5% w/w CPT-loaded films when compared to the HA or 0% CPT-loaded films (p < 0.05). No toxicity was observed in the rats following administration of these films.
CPT loaded films inhibited the formation of adhesions in the rat cecal sidewall abrasion model. HA crosslinked with 2 mM carbodiimide and containing 20% w/w glycerol and 0.6, 2.5 or 7.5% w/w CPT are flexible, mucoadhesive, biocompatible controlled release films that can be used to prevent adhesion formation.
To compare the antiadhesion efficacy of three agents (4% icodextrin, ferric hyaluronate gel, and Ringer's lactate) in severe peritoneal trauma caused by bipolar coagulation in a laparoscopic rat model.
Prospective, randomized, blinded experimental study.
International Laparoscopic Surgery Centre, Clermont-Ferrand, France.
Female Sprague-Dawley rats.
Animals were prospectively randomized to receive one of the three agents or to be controls. Coagulation of the parietal peritoneum was performed using a bipolar 40-W current followed by administration of an antiadhesion agent. Postoperative adhesion assessment was carried out on day 7 in 42 rats.
Adhesions were scored according to their extent and severity.
Adhesions occurred in all rats, however, adhesion and vascular adhesion rate scores were significantly higher in controls compared with treated groups. Adhesions were more likely to be filmy and easily separable in the 4% icodextrin group compared with the Ringer's lactate solution group.
Adhesion scores were decreased by the use of antiadherent agents. However, no rats were found to be free of adhesions after severe peritoneal trauma induced by 40-W bipolar coagulation of the peritoneum.