Use of dextran to prevent pericardial adhesions caused by maize starch powder

Maize starch powder, used as lubricant in surgical gloves, was administered into the pericardial cavity of rats and was found to induce granulomatosis with formation of pericardial adhesions. The effect of dextran 70 on the formation of these adhesions was investigated. It was found that intrapericardial dextran reduces the occurrence of pericardial adhesions.     

Prevention of pericardial adhesions with dextran 70

Pericardial adhesions pose a major problem during reoperative cardiac surgical procedures. The purpose of this study was to determine the effect of intrapericardial dextran 70 on the formation of pericardial adhesions in an animal model. The data obtained revealed that intrapericardial dextran 70 reduced the incidence of experimental pericardial adhesions.     

Prevention of adhesions after tubal surgery by use of dextran 70

Pelvic adhesions are a common cause of infertility. Moreover, their formation or redevelopment after corrective surgery of the fallopian tube is an important reason for surgical failure. Various agents for preventing adhesions have been described, but their efficacy has been poorly substantiated. The purpose of this article is to demonstrate that the use of high molecular weight dextran may be the first scientifically justifiable method for the prevention of adhesions after tubal surgery.     

Prevention of adhesions by high molecular weight dextran in rats. Re-evaluation in nine experiments.

The efficacy of 32% dextran 70 (Hyskon) in the prevention of postoperative peritoneal adhesions was evaluated in nine different experiments in a total of 320 rats under standardised conditions. Hyskon reduced adhesion formation, only in rats that were also subjected to abrasion of the caecum. In the remaining eight experiments Hyskon was ineffective. We conclude that more extensive experimental and clinical studies are desirable before this agent is recommended for prophylaxis against adhesions; any prophylactic regimen should be tested in a wide range of experiments. In addition, analysis of the control data suggested that the stimulus for inducing adhesions in some experiments was so strong that it could not be countered by any prophylactic regimen. A new microsurgical method that resulted in a 50 per cent response and an equal number of low grade and high grade adhesions was used. This method is well suited for investigation of both the stimulatory and the inhibitory effects of a test agent.     

High molecular weight dextran--effect on adhesion formation and peritonitis in rats

To evaluate the effect of 32% dextran 70 instillation on intra-abdominal adhesion formation and intestinal leaks, 100 animals were prospectively, randomly, and blindly treated with a sham laparotomy (n = 10), sham plus 5 ml dextran (10), intestinal abrasion plus 2 ml (20) or 5 ml (20) of dextran or saline, or intestinal division and anastomosis plus 2 ml (20) or 5 ml (20) of dextran or saline. Autopsies were performed on the animals without knowledge of treatment group at the time of death or sacrifice at 2 weeks. Adhesions were graded 0 to 3, anastomoses were examined for leaks, and the peritoneal cavity was searched for abscesses or peritonitis. Anastomosis produced more severe adhesions than abrasion. Dextran significantly (P greater than 0.01) reduced adhesion formation but resulted in peritonitis (5/40) rather than abscess (7/40) as seen with saline.     

Peritoneal healing with adhesion formation: current comment

Intra-abdominal adhesions are fibrotic structures, which lie in the form of a string or attachment between the abdominal organs and connect these together. They are responsible for serious clinical complications that include intestinal obstruction, infertility, and pelvic pain. During the last century, surgeons' comprehensive understanding of the biology of peritoneal healing and wound repair has allowed them to identify a variety of new therapeutic techniques that limit the development of adhesion formation. New drugs, dextran 70 and poloxamer 407, have been developed to prevent adhesion formation. In addition, three new biomaterials (oxidized regenerated cellulose, hyaluronate membrane, and polytetrafluoroethylene) are synthetic barriers being used to prevent adhesions.     

Peritoneal adhesion formation after lysis: inhibition by polyethylene glycol 4000.

Peritoneal adhesions cause much long-term postoperative morbidity. This study evaluates the efficacy of polyethylene glycol (PEG) 4000 in reducing adhesion reformation after lysis. Adhesions were induced, by abrasion, in 111 Sprague-Dawley rats at a first laparotomy. At a second operation, 10 days later, these adhesions were graded and lysed, after which the animals received one of the following solutions intraperitoneally: 5 per cent PEG 4000 (n = 21), 25 per cent PEG 4000 (n = 23), 32 per cent dextran 70 (n = 22) or isotonic saline (n = 25), or were left as an untreated control group (n = 20). When the reformed adhesions were graded after a further 10 days 5 per cent PEG 4000 was found to be the only solution that inhibited adhesion reformation. The adhesions that reformed in the other four test groups were significantly worse than when they were first graded (P less than or equal to 0.033 for all groups). Therefore 5 per cent PEG 4000 may be useful in clinical practice for the reduction of adhesion formation after lysis.     

An animal study of different treatments to prevent postoperative pelvic adhesions

A study was designed to test various high-molecular-weight solutions in the prevention of postoperative intraabdominal adhesions. The bicornuate rat uterus was used as the surgical model, and 80 mature white female rats underwent surgical injury of the right uterine horn. The rats were randomly divided into 5 groups: groups A, B, and C received 5 ml intraperitoneally of chondroitin sulfate, sodium carboxymethylcellulose, and 32% dextran 70, respectively; group D was treated with microsurgical repair; and group E, the control, received no therapy. The animals were killed postoperatively, and the adhesions were scored. Significantly better results in adhesion prevention were demonstrated in the sodium carboxymethylcellulose group vs. the other groups, except in group A where the difference was not significant.     

Metastasis formation after intravenous tumour cell injection in thrombocytopenic rats.

Induced thrombocytopenia has been found to decrease metastasis formation after intravenous tumour cell injection which emphasizes the importance of platelets in metastasis formation. Using a syngeneic 20-methylcholanthrene-induced fibrosarcoma in rats, the effect of platelet reduction was investigated in combination with trauma and infusion of dextran 1000. It was found that platelets were important for the increased formation of metastases after trauma but not for the increased formation of metastases after infusion of dextran 1000. Thus, trauma and dextran 1000 stimulate metastasis formation by different mechanisms. Possible explanations are discussed.     

Escin: Inhibiting Inflammation and Promoting Gastrointestinal Transit to Attenuate Formation of Postoperative Adhesions

Postoperative peritoneal adhesions are common, serious complications of general abdominal and gynecologic surgery that can lead to chronic abdominal pain, intestinal obstruction, and infertility. As yet, there are no ideal drugs that may be prescribed for patients to prevent adhesion formation effectively. In this study the effects of escin, a natural drug, on the various steps of adhesion formation were investigated. The effects of escin on increased vascular permeability induced by acetic acid in a mouse model of acute inflammation, granuloma formation in a subchronic inflammatory rat model, gastrointestinal transit in rats with intestinal paralysis, intestinal motility in postoperative patients, and postoperative adhesion formation in a rat model were observed. It was shown that escin could inhibit acute inflammation and granuloma formation, cause acceleration of gastrointestinal transit, help recover intestinal motility, and attenuate the formation of postoperative adhesions. The findings suggest that escin attenuates the formation of postoperative adhesions by inhibiting inflammation and promoting gastrointestinal transit. Thus it may be concluded that both inhibition of inflammation and increased gastrointestinal motility during the early postoperative period have a positive effect on decreasing the formation of adhesions.     

Flexor tendon healing and adhesion formation after Sterispon wrapping: a study in the rabbit

The influence of Sterispon (Allen & Hanbury) wrapping on the healing of the rabbit flexor digitorum profundus tendon sutured within the digital sheath was studied. Control tendons healed in 2 weeks in association with thick adhesions. The wrapped tendons were surrounded with fewer adhesions, but 50 per cent separated. Healing was delayed until adhesions reached the suture site. A sheath of a single layer of mesothelial cells formed on the surface of the Sterispon opposite the tendon and this markedly reduced adhesions at the suture site. The cellular reaction was bland.Sterispon wrapping had a similar effect on tendon healing and adhesion formation as wrapping with other non-absorbable substances and the results support the theory that healing in the digital sheath is necessarily mediated through the formation of adhesions. Sterispon wrapping has been helpful after tenolysis operations.     

Postsurgical adhesion formation in germfree and ex-germfree rats--a study using three scoring scales.

Postsurgical adhesions occur commonly after surgical procedures and are the source of substantial postoperative morbidity. No preventive or prophylactic regimen against adhesions has proven successful in all circumstances. The reasons for this are not clear. The basic mechanisms causing adhesion formation have not been elucidated fully, and furthermore, lack of accurate methods of measuring adhesions may be a contributing factor. Postoperative adhesions may occur in all kinds of surgery but are especially prominent in the abdomen, where the bowel flora may be a compromising factor. This study was undertaken to study the influence of the gastrointestinal microflora on adhesion formation. Germfree and ex-germfree DA rats were subjected to a cecal crush model, and adhesions were evaluated after 7 days using 3 different scoring scales. Germfree rats formed significantly fewer adhesions than their ex-germfree (conventionalized) counterparts. The differences were so great that all three scoring scales achieved significance (p < .005). This study corroborates that the endogenous bowel flora per se is involved in adhesion formation without causing frank infection.     

Reoperation for small intestinal obstruction

Today, intestinal adhesions represent the most frequent etiology for complete or partial intestinal obstruction. Although partial obstruction can be treated nonoperatively with a considerable likelihood of success, intestinal strangulation cannot uniformly be predicted or prevented. Complete intestinal obstruction is associated with a significant incidence of strangulation if not treated by a vigorous surgical approach. Consequently, complete intestinal obstruction secondary to adhesions is still a surgical disease. Attempts at control of the adhesion process include mechanical methods to prevent subsequent obstruction and chemical methods to prevent the adhesion process itself. The invasive mechanical methods appear dated. A variety of agents have been used either systemically or in the peritoneal cavity to prevent the establishment of intra-abdominal adhesions. Agents that do not contribute to subsequent morbidity or impede the native host defense mechanisms should be utilized. High-molecular-weight dextran and nonsteroidal anti-inflammatory agents show some promise of being both safe and effective. As is frequently the case, the bottom line in preventing and treating intra-abdominal adhesions is appropriate surgical technique. Intestinal adhesions can be related clearly to leaving damaged, devitalized, or ischemic tissue in the peritoneal cavity or to excessive roughness in handling of tissues. Steps such as avoidance of excessive suture material and unnecessary handling of the bowel will do much to prevent subsequent adhesion generation. Likewise, the surgical lysis of intraperitoneal adhesions is frequently fraught with complications such as intra-abdominal abscess or postoperative incisional failure. This is again related to surgical technique and most directly to the use of blunt dissection to divide adhesions. Knife dissection in the lysis of adhesions is recommended. This technique, combined with excellent intraoperative hemostasis, can be associated with a marked diminution in the incidence of postoperative fistulas and abscesses.     

Reduction of retrosternal and pericardial adhesions with rapidly resorbable polymer films.

BACKGROUND: The formation of postoperative cardiac adhesions makes a repeat sternotomy time consuming and dangerous. Many attempts have been made to solve this problem by using either drugs to inhibit fibrinolytic activity or different types of pericardial substitutes. The results have not been satisfactory. METHODS: The efficacy of bioresorbable film prototypes made of polyethylene glycol (EO) and polylactic acid (LA) (EO/LA = 1.5, 2.5, and 3.0) in the prevention of adhesions after cardiac operations in canine models was tested. After desiccation and abrasion of the epicardium, a transparent bioresorbable film was placed over the heart. The pericardium was closed to allow intrapericardial adhesions (n = 32) or left open and attached to the chest wall to induce retrosternal adhesions (n = 17). Postoperative recovery was similar among the groups. Retrosternal and pericardial adhesions were evaluated at necropsy 3 weeks later by assessing area, tenacity, and density of the adhesions. RESULTS: In the control dogs, tenacious, dense adhesions were observed. In contrast, adhesion formation was reduced at all sites covered by the films. The bioresorbable films were efficacious in the reduction of adhesion formation between epicardium and pericardium or between epicardium and sternum after cardiac operation. The EO/LA 1.5 film most effectively prevented the early adhesions. CONCLUSIONS: The bioresorbable films (EO/LA = 1.5, 2.5, and 3.0) significantly reduced adhesion formation, with EO/LA = 1.5 (Repel CV) being optimal. As the barrier was rapidly resorbed, the capsule formation induced by permanent barriers was avoided.     

Cianidanol ( [+]-cyanidanol-3) prevents the development of abdominal adhesions in rats

Abdominal adhesions were experimentally induced in rats by gentle scraping. Severe adhesions developed in 38.7% of the control animals. The flavonoid cianidanol ( [+]-cyanidanol-3), an in vitro inhibitor of procollagen production, was administered intragastrically or intraperitoneally in doses of 9 to 72 mg per rat. Administered intraperitoneally at a dose of 36 or 72 mg per rat, cianidanol substantially inhibited adhesion formulation, when given immediately, three days, or five days after surgery. Oral administration of the drug was less effective in preventing the formation of adhesions. Thimerosal, another connective-tissue inhibitor, was found to be toxic at doses of 2.5 or 5 mg per rat, and its effect on the prevention of adhesion formation was poor. The ability of cianidanol to inhibit the development of abdominal adhesions in rats suggests that a possible approach to treatment is to inhibit the production of procollagen and thus prevent the formation of the collagenous fibers that are the cause of adhesions.     

Prevention of pericardial adhesions with N-O carboxymethylchitosan in the rabbit model.

The presence of mediastinal adhesions significantly increases the morbidity and mortality of reoperative cardiac surgical procedures. Previous investigations have reported on the therapeutic utility of topical hydrogels in reducing the formation of postsurgical adhesions. The goal of the present study is to evaluate the ability of N-O carboxymethylchitosan (a glycosaminoglycan hydrogel derivative) to reduce the formation ofpostsurgical pericardial adhesions in a large-animal model. Sixteen adult New Zealand white rabbits were randomly assigned to one of two treatment groups. Group 1 subjects (n = 8) had N-O carboxymethylchitosan directly applied to the heart and retrosternal surfaces after sternotomy was performed, while subjects in group 2 (n = 8) had saline applied to these areas. After a period of 14 days the animals were sacrificed under anesthesia, and independent observers, blinded to treatment, graded the formation of pericardial adhesions. The severity of adhesion formation was significantly less in the group treated with N-O carboxymethylchitosan (p < .01). This study demonstrates that N-O carboxymethylchitosan markedly decreases the formation of poststernotomy adhesions in a large-animal model without untoward cardiac side effects. This hydrogel derivative may prove to be of great therapeutic value when used prophylactically in the setting of cardiac surgery.     

Adhesion formation can be reduced by the suppression of transforming growth factor-beta1 activity.

Surgery or trauma often results in restrictive adhesions around joints or tendons that cause severe functional impairment. The formation of adhesion is essentially a fibrogenetic process; therefore, peptide growth factors, such as transforming growth factor-beta, are assumed to play central roles in its development. The purpose of this study was to test the hypothesis that suppression of transforming growth factor-beta1 activity reduces adhesion formation. Sixty rabbits were prepared and randomly divided into six groups of 10. Intraarticular adhesions were created in the right knee joints by cortical bone shaving and subsequent cast immobilization for 4 weeks. In animals in three of the six groups, transforming growth factor-beta1 activity was suppressed by continuous administration of the neutralizing antibody in three graded doses; animals in the other three groups were used as controls. Four weeks after the surgery, the casts were removed and the adhesions were assessed macroscopically, histologically, biomechanically, and biochemically. Gross observation showed that the neutralizing antibody had suppressed adhesion formation in a dose-dependent manner. This is consistent with biomechanical measurement results demonstrating that the antibody reduced the flexion contractures. Histologically, the adhesion in our model was fibrous tissue and the adhesions in the animals in the antibody groups were thin and loose in comparison with the controls. Biochemical analyses further supported these results, demonstrating that administration of the antibody reduced collagen content in the adhesions with a predominance of type-I collagen. Thus, this study showed that suppression of the actions of transforming growth factor-beta1 reduced adhesion formation. Considering the various possible measures to control the activity of the growth factor, suppression of transforming growth factor-beta may be a novel, potent approach to preventing adhesions.     

Peritoneal adhesions to prosthetic materials

BACKGROUND: In many cases, incisional hernia repair requires the use of prosthetic materials. The aim of this experimental study in a rat model was to assess the role of polyglactin 910 mesh and fluoropassivated polyester mesh in preventing the formation of adhesions. METHODS: In the first experiment, the formation of peritoneal adhesions was assessed after insertion of polypropylene, polypropylene combined with polyglactin 910, or no mesh. In the second experiment, adhesion formations were compared after insertion of fluoropassivated polyester, polypropylene, and no mesh. RESULTS: The first experiment showed no significant difference in adhesion formations between the polypropylene mesh and the combined mesh; however, when no mesh was used, there were significantly fewer adhesions in both experiments (p < 0.01). The second experiment showed a significantly lower degree of adhesions and a lower Adhesion Index after insertion of fluoropassivated polyester mesh than when polypropylene mesh was used (p = 0.04). CONCLUSIONS: Adding polyglactin 910 mesh to polypropylene mesh to prevent the formation of adhesions is not an effective measure. Fluoropassivated polyester meshes appear to provide a better alternative to the use of polypropylene meshes for incisional hernia repair in humans in terms of the formation of adhesions.     

Prevention of Pericardial Adhesions with N-O Carboxymethylchitosan in the Rabbit Model

The presence of mediastinal adhesions significantly increases the morbidity and mortality of reoperative cardiac surgical procedures. Previous investigations have reported on the therapeutic utility of topical hydrogels in reducing the formation of postsurgical adhesions. The goal of the present study is to evaluate the ability of N-O carboxymethylchitosan (a glycosaminoglycan hydrogel derivative) to reduce the formation of postsurgical pericardial adhesions in a large-animal model. Sixteen adult New Zealand white rabbits were randomly assigned to one of two treatment groups. Group 1 subjects (n = 8) had N-O carboxymethylchitosan directly applied to the heart and retrosternal surfaces after sternotomy was performed, while subjects in group 2 (n = 8) had saline applied to these areas. After a period of 14 days the animals were sacrificed under anesthesia, and independent observers, blinded to treatment, graded the formation of pericardial adhesions. The severity of adhesion formation was significantly less in the group treated with N-O carboxymethylchitosan (p &lt; .01). This study demonstrates that N-O carboxymethylchitosan markedly decreases the formation of poststernotomy adhesions in a large-animal model without untoward cardiac side effects. This hydrogel derivative may prove to be of great therapeutic value when used prophylactically in the setting of cardiac surgery.     

Dextrans and the formation of pulmonary metastases after intravenous tumour cell injection in rats non-sensitive to dextran.

This study showed, that in a syngeneic tumour-host system in rats non-sensitive to dextran, dextran 40 and dextran 100 did not stimulate metastasis formation after intravenous tumour cell injection, neither when given as intravenous pretreatment nor when given in the tumour cell suspension. Dextran 1000 stimulated the formation of metastases in both these situations. Disturbed microcirculation, intravascular coagulation and effects upon the tumour cell membrane appear to be the main resons, why dextran 1000 stimulated metastasis formation under the experimental conditions used.