Development Of Postoperative Adhesions Research Articles

Halofuginone infused keratin hydrogel attenuates adhesions in a rodent cecal abrasion model

BackgroundPostoperative adhesion formation continues to be a significant surgical complication, and methods for preventing abdominopelvic adhesions remain limited. Halofuginone (HF) is a type-1 collagen synthesis inhibitor and may enhance the effects of a physical barrier in preventing adhesion formation. We evaluated the effectiveness of a HF infused keratin hydrogel on preventing adhesions in a rat cecal abrasion model. Material and methodsLaparotomy and standardized cecal abrasion was performed on 58 retired-breeder Sprague Dawley female rats to induce intra-abdominal adhesions. Rats were randomized to: no treatment; Interceed absorbable adhesion barrier; keratin hydrogel alone; or keratin hydrogel infused with 22 μg/mL of HF. Necropsies were performed at postop d-14 to assess the extent and tenacity of adhesions and grade histologic inflammation and fibrosis using a standard scoring system. Serum, liver, kidneys, and lungs were harvested to evaluate tissue HF concentrations. Protein and drug elution curves were generated to assess the release of HF from the hydrogel. ResultsTreatment with Keratin-HF hydrogel resulted in significantly fewer abdominal adhesions than any other treatment, and significantly less dense adhesions compared with Interceed or keratin hydrogel alone. Subset histologic analysis did not reveal qualitative differences. HF was undetectable in serum and kidneys, and detected at negligible concentrations in liver and lungs. Keratin-HF hydrogel drug release in phosphate-buffered solution (PBS) was sustained over 7 d and correlated with keratin protein degradation. ConclusionsKeratin-HF hydrogel is a novel therapeutic agent that may provide a better method for preventing the development of postoperative adhesions using a combined physical barrier and pharmacologic approached.

Effect of Lyophilized Amniotic Membrane on the Development of Adhesions and Fibrosis after Extraocular Muscle Surgery in Rabbits

Purpose: To histopathologically evaluate the influence of lyophilized human amniotic membrane transplant on the development of postoperative adhesions and fibrosis after extraocular muscle surgery.Methods: Ten albino rabbits were used. The superior rectus muscle was resected 4 mm in both eyes. In right eyes, the superior rectus muscle was wrapped with lyophilized (air-dried, freeze-dried) human amniotic membrane (group AM). In left eyes, the superior rectus muscle was not wrapped with amniotic membrane, and served as a control group (group C). The rabbits were sacrificed and the eyes were enucleated 6 weeks after surgery to perform histopathological examination.Results: Two rabbits died 1 week after surgery and were excluded. Histopathological evaluation of both eyes of the remaining 8 rabbits was done. The amniotic membrane was not seen in all eyes. On comparing eye pairs of each rabbit, right eyes showed significantly less conjunctival inflammation (p = 0.034), but insignificantly less foreign body inflammation (p = 0.625), adhesions between sclera and muscle (p = 0.206), muscle fibrosis (p = 1.000), and conjunctival hyperemia (p = 0.059) as compared to left eyes.Conclusions: Lyophilized amniotic membrane insignificantly reduces postoperative adhesions and fibrosis, when used to wrap the operated upon extraocular muscles, limiting the benefit of this membrane in strabismus surgery.

Formation and clinical importance of postoperative peritoneal adhesions

Abdominal adhesions following abdominopelvic surgical interventions are well-known causes of increased morbidity and mortality at early and late postoperative period. It is suggested that intraabdominal adhesions are thought to be developed secondary to peritoneal or bowel serosal surface trauma, foreign body reaction and ischemia. In present study, development and clinical importance of postoperative peritoneal adhesions are discussed together with literature knowledge.

Exposure to polychlorinated biphenyls enhances lipid peroxidation in human normal peritoneal and adhesion fibroblasts: A potential role for myeloperoxidase

Nitric oxide, superoxide, and lipid peroxidation (LPO) produced under oxidative stress may contribute to the development of postoperative adhesions. The objective of this study was to determine the effects of polychlorinated biphenyls (PCBs) on LPO, superoxide dismutase, myeloperoxidase (MPO), and nitrite/nitrate in human normal peritoneal and adhesion fibroblasts. PCB treatment reduced inducible nitric oxide synthase (iNOS) expression as well as levels of nitrite/nitrate in both cell lines. Although there was no difference in iNOS expression between the two cell lines, adhesion fibroblasts manifested lower basal levels of MPO compared to normal peritoneal fibroblasts. There was a reduction in MPO expression and its activity in response to PCB treatment in normal peritoneal fibroblasts; however, this effect was minimal in adhesion fibroblasts. Moreover, adhesion fibroblasts manifested higher levels of LPO compared to normal peritoneal fibroblasts, whereas PCB treatment increased LPO levels in both cell types. We conclude that PCBs promote the development of the adhesion phenotype by generating an oxidative stress environment. This is evident by lower iNOS, MPO, and nitrite/nitrate and a simultaneous increase in LPO. Loss of MPO activity, possibly through a mechanism involving MPO heme depletion and free iron release, is yet another source of oxidative stress.

Hypoxia induces transforming growth factor beta 1 (TGFβ1) in human macrophages through a hypoxia inducible factor 1α (HIF-1α) – dependent mechanism

OBJECTIVE: Hypoxia is a main trigger in the development of post-operative adhesions. Exposure of normal peritoneal fibroblasts to hypoxia induces the adhesion phenotype, which is characterized by increased levels of TGFβ1 and Collagen-I (Col-I). Hypoxia exerts its effects, in part by, a HIF1α-dependent mechanism. The role of macrophages in the development of the adhesion phenotype is not well understood. Therefore, the objective of this study is to determine whether hypoxia induces the expression of TGFβ1 in human macrophages in a mechanism involving HIF1α.

Prevention of Postoperative Peritoneal Adhesions by Administration of Estrogen

Aim: Postoperative abdominal adhesions represent one of the most common causes of intestinal obstruction in surgical patients. In this study, the effects of intraperitoneal administration of estrogen on the development of postoperative intraabdominal adhesions and peritoneal leucocytes in a rat adhesion model were investigated. Methods: Sixty Wistar albino rats were divided into three groups. Group 1 (control group) had their abdomen closed after surgery without administration of any material or drug. Group 2 (saline group) received 2 ml of 0.9% NaCl, and group 3 (estrogen group) animals received a single intraperitoneal dose of 2 cc (1 mg) estrogen (Estradiol propionate, 50.000U, Akrofilline®, Biofarma, Turkey). All the groups were exposed to the same adhesion-creating procedure (Swolin K. Experimental studies on the prevention of intra-abdominal adhesions. Studies on rats with an emulsion of lipid and prednisolone. Acta Obstet Gynecol Scand. 1966;45:473–498.). After 7–42 days, all animals were sacrificed. Adhesions were scored and peritoneal leucocytes were counted. Results: The adhesion formation and peritoneal leucocyte count of the estrogen group were significantly less than the control and saline groups and a statistically significant difference was determined in comparison of those groups (p <. 05). Conclusion: We concluded that intraperitoneal estrogen decreases the incidence of postoperative intraabdominal adhesion formation in rat adhesion model.

Administration of honey to prevent peritoneal adhesions in a rat peritonitis model

Aim We investigated the effects of intraperitoneal honey on the development of postoperative intra-abdominal adhesions and oxidative stress in a model of bacterial peritonitis. Methods Bacterial peritonitis was induced in 18 rats by cecal ligation and puncture. The rats were randomly assigned to three groups. Group 1 ( n = 6) received honey intraperitoneally, group 2 ( n = 6) received 5% dextrose intraperitoneally, and the third group received no fluid or medicine intraperitoneally one day after cecal ligation and puncture procedure. All animals were killed 14 days later so we could assess the adhesion score. Tissue antioxidant levels were measured in 1-g tissue samples taken from the abdominal wall. Results Adhesion scores of honey treated group were significantly lower according to the control group ( P < 0.05) and statistically significant. Adhesion scores of honey were lower from 5% dextrose but not statistically significant ( P > 0.05). Malondialdehyde values of honey group were significantly lower from the control group ( P < 0.05) and levels in 5% dextrose group was higher than the honey group. Catalase levels were high in control and 5% dextrose groups. Superoxide dismutase levels were higher in the control group than the honey group (statistically significant). Conclusions Intraperitoneal honey decreased the formation of postoperative intra-abdominal adhesions without compromising wound healing in this bacterial peritonitis rat model. Honey also decreased the oxidative stress during peritonitis.

Postoperative Adhesions: From Formation to Prevention

Postoperative intra-abdominal and pelvic adhesions are the leading cause of infertility, chronic pelvic pain, and intestinal obstruction. It is generally considered that some people are more prone to develop postoperative adhesions than are others. Unfortunately, there is no available marker to predict the occurrence or the extent and severity of adhesions preoperatively. Ischemia has been thought to be the most important insult that leads to adhesion development. Furthermore, a deficient, suppressed, or overwhelmed natural immune system has been proposed as an underlying mechanism in adhesion development. The type of surgical approach (laparoscopy or laparotomy) and closure of peritoneum in gynecologic surgeries and cesarean section have been debated as important factors that influence the development and extent of postoperative adhesions. In this article, we have reviewed the current state of adhesion development and the effects of barrier agents in prevention of postoperative adhesions.

Effects of pyrolytic carbon on postoperative adhesion formation in rats

Peritoneal adhesion is a consequence of wound healing that sometimes causes severe postoperative complications. Despite all the preventive measures and agents, adhesions have still not been eliminated completely. The aim of this study was to evaluate the effects of pyrolytic carbon on the development of postoperative peritoneal and uterine tube adhesions. Twenty female Wistar-Albino type rats were used in this study. The rats were divided into two groups: treatment and control groups. After ketamine anaesthesia (50 mg/kg IM), a lower midline abdominal incision was performed and a standard uterine lesion was created by electrocauterization. In the study group, pyrolytic carbon was applied to the surface of the uterus and no additional procedure was applied in the control group. After 2 weeks, all of the rats were killed and uterine adhesions were staged according to the Leach scoring system. In the control group, the total adhesion score was 8.8 +/- 0.42. In the study group, the total adhesion score was 3.3 +/- 1.49, significantly lower than that in the control group (P < 0.001). Pyrolytic carbon significantly reduces the prevalence of peritoneal and uterine tube adhesion formation in rats. However, further more detailed investigations are needed before this material is used in clinical practice.

Influencing factors of adhesion development and the efficacy of adhesion-preventing agents in patients undergoing laparoscopic myomectomy as evaluated by a second-look laparoscopy

To examine the factors influencing the development of adhesions after laparoscopic myomectomy (LM) and the efficacy of adhesion-preventing agents. Prospective nonrandomized study. University-affiliated hospital. Three hundred seventy-two patients who underwent LM alone by the same surgeon between 2000 and 2005 were included for the analysis in this study. Video tape recording was performed during the second-look laparoscopy (SLL) to evaluate the postoperative uterine wound adhesions and adhesions around the uterine adnexa. Statistical workup was conducted using logistic regression analysis. Evaluation of adhesions at the uterine wound and of de novo adhesions of the uterine adnexa by SLL. The SLL revealed uterine surgical wound adhesions in 141 patients (37.9%) and de novo adhesions of the uterine adnexa in 33 patients (8.9%). The results of analysis to determine the factors influencing the development of postoperative adhesions revealed that the diameter of the largest myoma, number of myomas, and type of adhesion-preventing agent used (except for fibrin sheath, which had no effect) influenced the incidence of postoperative adhesions at the surgical wound, but only the diameter of the largest myoma influenced the incidence of de novo adhesions of the uterine adnexa. Development of surgical wound adhesions after LM can be prevented by the use of an appropriate adhesion-preventing agent.

Adenovirus-mediated expression of cyclooxygenase-2 antisense reverse abnormal genetic profile of human adhesion fibroblasts

To determine the effects of blocking the translation of cyclooxygenase-2 (COX-2) mRNA on the mRNA levels of type I collagen, type III collagen, fibronectin, and transforming growth factor-beta (TGF-beta1) in fibroblasts obtained from normal peritoneal and adhesion tissues. Prospective experimental study. University medical center. Fibroblasts established from peritoneal and adhesion tissue of the same patients. Adenovirus with COX-2 treatment of the primary cultured fibroblasts. Fibroblasts of normal peritoneal and adhesion tissues were isolated from the same patients. Adhesion and normal peritoneal fibroblasts were transfected with an adenovirus COX-2 mRNA in sense or antisense orientation. RNA was extracted from each treatment and subjected to real time reverse transcriptase-polymerase chain reaction to quantify change in mRNA levels of type I collagen, type III collagen, fibronectin, and TGF-beta1. Type I collagen, type III collagen, fibronectin, and TGF-beta1 mRNAs were present in both normal peritoneal and adhesion fibroblasts with significantly higher levels in adhesion fibroblasts. Normal fibroblasts transfected with the COX-2 sense virus exhibited an elevated mRNA level in those molecules that reached the mRNA levels seen for adhesion fibroblasts. There were no effects seen on the mRNA levels in those molecules when adhesion fibroblasts were transfected with COX-2 sense virus. Normal fibroblasts transfected with COX-2 antisense virus exhibited no difference in mRNA levels in those molecules as compared with untransfected controls. In contrast, adhesion fibroblasts transfected with COX-2 antisense exhibited markedly reduced mRNA levels in those molecules to levels that were seen in normal peritoneal fibroblasts. Our data suggest that inhibition of COX-2 may reduce the development of postoperative adhesions by preventing the formation of the adhesion phenotype.

The effect of resveratrol on prevention of the development of postoperative adhesions in a rat model

Objective. Our aim was to investigate the anti-adhesion potential of resveratrol, a phytoestrogen naturally found in wine, in a rat uterine horn model.Methods. Lesions were created by laparotomy in the uterine horn of 70 rats, randomized before the operation into seven groups consisting of ten animals each: (1) control group, no adjuvant therapy; (2) intraperitoneal (IP) application of the resveratrol dilution vehicle, 10 mg/kg, before closing the laparotomy; (3) subcutaneous (SC) injection of dilution vehicle, 10 mg/kg, 30 min before the operation; (4) IP application of resveratrol, 10 mg/kg, before closing the laparotomy; (5) SC injection of resveratrol, 10 mg/kg, 30 min before the operation; (6) IP application of resveratrol, 10 mg/kg, before closing the laparotomy and continued SC daily for 5 days; and (7) SC injection of resveratrol, 10 mg/kg, 30 min before the operation and continued SC daily for 5 days. On the 14th postoperative day adhesion scores were determined. Levels of thiobarbituric acid-reactive substances and total antioxidant capacity (TAC) were also measured.Results. In animals treated with repeated SC resveratrol, adhesions were graded as significantly less severe than in the vehicle control group or the groups treated with resveratrol IP or IP plus SC. TAC of control group rats was significantly lower than that of animals treated with repeated SC resveratrol.Conclusion. Repeated SC resveratrol significantly reduces adhesion formation.

Intraperitoneal Tenoxicam to Prevent Abdominal Adhesion Formation in a Rat Peritonitis Model

We investigated the effects of intraperitoneal tenoxicam on the development of postoperative intra-abdominal adhesions and oxidative stress in a model of bacterial peritonitis. Bacterial peritonitis was induced in 24 rats by cecal ligation and puncture. The rats were randomly assigned to one of three groups. Group 1 (n = 8) received 2 ml saline intraperitoneally, group 2 (n = 8) received 2 ml (0.5 mg/kg) tenoxicam (Oksamen) intraperitoneally, and group 3 (n = 8) was a control, which did not receive any injection. All animals were killed 14 days later so we could assess the adhesion score and measure anastomotic bursting pressures. Tissue antioxidant levels were measured in 1-g tissue samples taken from the abdominal wall. The adhesion score was significantly lower in the tenoxicam group than in the saline and control groups. The anastomotic bursting pressures were higher in the saline and tenoxicam groups than in the control group. The catalase (CAT) levels were higher in the saline and tenoxicam groups than in the control group. The malondialdehyde (MDH) levels were higher in the saline group than in the tenoxicam and control groups. Intraperitoneal tenoxicam inhibited the formation of postoperative intra-abdominal adhesions without compromising wound healing in this bacterial peritonitis rat model. Tenoxicam also decreased the oxidative stress during peritonitis.

The Effect of Opioids on the Development of Postoperative Intra-Abdominal Adhesions

People addicted to opium rarely develop intra-abdominal adhesions after abdominal surgery. We aimed to evaluate the effect of opium or morphine on preventing postoperative adhesions in rats. Sixty-three rats were randomly divided into a control group, opium-addicted group, and morphine-addicted group in a double-blind study. Drug dependency was checked by using naloxone. Animals were then operated on and the cecum was abraded. At reoperation 3 weeks later the magnitude of adhesions was evaluated by a scoring system. There was a significant difference between the control, opium-addicted, and morphine-addicted groups with regard to the length (P < .001), thickness (P < .05), and severity of adhesions (P < .05). Opium or morphine reduces the severity of postoperative adhesions. Elucidation of the opioid receptor(s) involved in this process would enable the use of selective ligands and offer a pharmacologic strategy in preventing adhesion formation.

Experimental study of starch-induced intraperitoneal adhesions

The effects of starch on the development of postoperative adhesions were examined in 144 Sprague Dawley rats. Groups of rats were injected intraperitoneally with suspensions of washings from starched gloves, starch-free gloves and starch-poor washed gloves, and after operative manipulation of the bowel. The incidence of adhesions was greatest (78 per cent) after laparotomy and injections of starch-rich washings and least when starch-poor (33 per cent) or starch-free glove suspensions (37 per cent) were used, confirming an advantage for washing gloves or switching to starch-free products.

The aetiology of post-operative abdominal adhesions. An experimental study.

This experimental study was designed to test the hypothesis that it is not serosal integrity but tissue ischemia which is the important etiological factor in the development of fibrous postoperative adhesions and that these adhesions represent not scar tissue but vascular grafts from adjacent healthy organs into a devascularized substrate. Experiments were performed on male albino rats. The experiments included the following: mesenteric division experiments polyurethane-wrap experiments omental graft experiments and adhesion formation in relation to the parietal peritoneum. The findings indicate that fibrous adhesions developed in relation to areas of ischemia induced either in the small intestine or on the parietal peritoneal wall of rats. The adhesions seemed to be vascular grafts from adjacent viable structures and could provide sufficient blood supply to their host tissues to maintain viability. The nature of the stimulus which provokes adhesions to form to ischemic tissue remains a subject for speculation. In terms of operative procedures there is at present nothing to indicate that reperitonealization prevents the development of postoperative adhestions.

Evaluation of implant/host tissue interactions following intraperitoneal implantation of porcine dermal collagen prosthesis in the rat

An ideal prosthesis for ventral hernia repair should minimize development of postoperative adhesions. This study evaluates adhesion formation following intraperitoneal implantation of acellular porcine dermal collagen (PDC) and polypropylene (PP) mesh in 16 rats. Implant placement alternated left/right. Sacrifice (4 or 12 weeks) was randomized. Methods included adhesion grading (extent, severity, required dissection method) and histological evaluation. At 4 weeks, 7 of 8 PDC specimens and 0 of 8 PP implants were adhesion-free; results were identical at 12 weeks. Four-week adhesions were less developed than 12-week adhesions. Histology showed mononuclear cell foreign body reaction and disorganized collagen deposition for PPs compared to infiltration with neovascular channels and qualitatively less intense foreign body reaction for PDCs. PDC exhibits fewer adhesions and more favorable cellular response than PP in the rat.

Possible Role of Natural Immune Response Against Fibroblasts in the Development of Post-Operative Adhesions

Intraperitoneal adhesion development following abdominal surgery is a prevalant complication. Fibroblasts obtained from the adhesion tissue (AT) differ from normal peritoneal (NP) fibroblasts in several aspects. Innate immune responses, executed partially by lymphocytes, participate in the elimination of altered cells for the homeostasis of the body. In this study, we investigated NP and AT fibroblast expression patterns of immune response-related markers and lymphokine-activated killer (LAK) cell-mediated fibroblast elimination in vitro.

Three-layered synthetic pericardial substitutes reduce postoperative pericardial adhesions

Background The development of postoperative pericardial adhesions increases the risk of cardiac reoperations. The purpose of this study was to test a new pericardial substitute (UBE sheet; UBE Industries, Ltd, Tokyo, Japan) that consists of 3 layers, namely, a middle layer of polyester inserted between 2 layers of silicone-urethane copolymer. Methods Before implantation into the animals, platelet adhesion to the UBE sheet was evaluated in vitro. In the canine model, the UBE sheet (group I; n = 6) was implanted for 3 months. The development of adhesions, epicardial reactions, the shrink ratio of the patch, and macrophage infiltration to the epicardium with histologic examination were evaluated. As a control, an expanded polytetrafluoroethylene sheet (group II; n = 5) was implanted in the same manner. Results Scanning electron microscopy of the platelets adhered to the sheet showed that the UBE sheet was superior in biocompatibility compared with the expanded polytetrafluoroethylene sheet. In the canine study, group I showed fewer adhesions than group II (median [25th percentile, 75th percentile]: 0.0 [0.0, 0.0] vs 1.0 [1.0, 2.3]; P = .003; Mann-Whitney U test), fewer epicardial reactions (1.75 [1.0, 3.0] vs 3.0 [3.0, 3.0]; P = .034), and a smaller shrink ratio (8.0% [5.5%, 12.4%] vs 31.7% [30.0%, 44.8%]; P = .006). Immunohistologic studies showed fewer macrophage infiltrations (86 [56.8, 139.3] vs 201 [161.0, 276.5] in 3 fields; P = .045) into the epicardium of group I. Conclusions The new 3-layered pericardial substitute clearly reduced adhesion formation. We concluded that this sheet may cause fewer adhesions and a less severe inflammatory reaction after cardiac surgery, thereby facilitating safe adhesiolysis reoperation.

Regulation of expression of tissue plasminogen activator and plasminogen activator inhibitor-1 by dichloroacetic acid in human fibroblasts from normal peritoneum and adhesions

ObjectiveAs part of our ongoing studies to understand the biologic mechanisms of wound repair that lead to postoperative adhesions, we have identified characteristics of an adhesion phenotype that differs between fibroblasts that are obtained from human normal peritoneum and adhesions. In this study, we sought to examine whether stimulation of aerobic metabolism would alter differential expression of tissue plasminogen activator and plasminogen activator inhibitor–1, thereby creating a milieu likely to be less favorable to postoperative adhesion development. To examine this issue, we used a compound, dichloroacetic acid, that stimulates the pyruvate dehydrogenase complex, which causes pyruvate to be metabolized in the Kreb's cycle rather than being converted into lactate, thereby switching anaerobic to aerobic metabolism. Study designHuman fibroblasts from normal peritoneum and adhesions were cultured in the absence or presence of dichloroacetic acid (100 μg/mL) for 24 hours, under normal and hypoxic (2% 02) conditions. Real-time reverse transcriptase–polymerase chain reaction of tissue plasminogen activator, plasminogen activator inhibitor–1, and a housekeeping gene β-actin was performed with messenger RNA that was extracted from all treatment points. ResultsDichloroacetic acid stimulated normal peritoneal fibroblast tissue plasminogen activator messenger RNA expression under hypoxic conditions. In adhesion fibroblasts, dichloroacetic acid treatment enhanced tissue plasminogen activator messenger RNA expression under both normoxic and hypoxic conditions. Plasminogen activator inhibitor–1 messenger RNA expression was unaltered by dichloroacetic acid in normoxic normal peritoneal fibroblasts; but during culture under hypoxic conditions, dichloroacetic acid reduced plasminogen activator inhibitor–1 messenger RNA expression. Similarly, in adhesion fibroblasts, dichloroacetic acid reduced plasminogen activator inhibitor–1 messenger RNA expression under both normoxic and hypoxic conditions. As a result, in normal peritoneal fibroblasts under hypoxic conditions and in adhesion fibroblasts under normoxic and hypoxic conditions, dichloroacetic acid greatly increased the tissue plasminogen activator/plasminogen activator inhibitor–1 ratios. ConclusionThese findings confirm that fibroblasts from adhesions are characterized by reduced tissue plasminogen activator and increased plasminogen activator inhibitor–1 production. These observations are extended to show the stimulation of oxidative metabolism by dichloroacetic acid increases tissue plasminogen activator expression under hypoxic conditions. Dichloroacetic acid reduces plasminogen activator inhibitor–1 production by hypoxic normal peritoneal fibroblasts and adhesion fibroblasts under hypoxic conditions. The resultant increases in the tissue plasminogen activator/plasminogen activator inhibitor–1 ratios would favor the development of a fibrinolytic milieu, which would be expected potentially to limit postoperative adhesion development. Thus, regulation of metabolic activity of peritoneal cells may provide a target for future interventions for the reduction of the development of postoperative adhesions, particularly as intervention relates to the healing of peritoneal sites that previously had adhesions. (eg, sites of potential adhesion reformation).