Peritoneal Adhesion Formation Research Articles

Enteric bacteria and their antigens may stimulate postoperative peritoneal adhesion formation

Intraabdominal sepsis causes exuberant inflammation, which results in dense adhesions. Translocation of enteric bacteria and/or their antigens after laparotomy may therefore also affect peritoneal healing by promoting local release of proinflammatory cytokines. Our hypothesis was that targeted counter therapy could be beneficial if such contamination was to augment postoperative adhesion formation. Two endotoxin-hyposensitive mouse strains (C3H/HeJ and C57BL/10ScCr) and their syngeneic counterparts (C3H/HeN and C57BL10/ScSn, respectively) underwent reproducible adhesion-inducing operation (AIO) (n=10/group) with sacrifice and blinded adhesion grading 14 days later. In addition, CD-1 mice were gavaged with fluorescein isothiocyanate labeled-lipopolysaccharide (FITC-LPS) prior to either AIO or sham laparotomy and had both peritoneal macrophages and circulating monocytes assessed by flow cytometry afterward. The cytokine-release response of resident peritoneal cells to LPS stimulation was assessed in vitro (murine peritoneal mast cell cultures) and in vivo (unoperated CD-1 mice administered LPS intraperitoneally [10 & 50 microg/mouse]). Finally, CD-1 mice (n=10/group) had AIO and received either bactericidal/permeability increasing protein (rBPI, 2 mg/mouse) or vehicle solution in the early postoperative period with assessment of adhesion formation 2 weeks later. Both HeJ and ScCr mice had less adhesions than their controls (P=.0015 and .0001, respectively, Mann Whitney U test). FITC-LPS uptake by peritoneal macrophages was striking after AIO. Intraperitoneal LPS provoked significant local vascular endothelial growth factor (VEGF) release as did the process of AIO. In vitro, LPS induced significant interleukin-(IL)-6 release from isolated mast cells. Intraperitoneal administration of rBPI to CD-1 mice early after AIO markedly attenuated subsequent adhesion formation (P=.0003). Peritoneal adhesion formation is exacerbated by peritoneal contamination due to translocation after laparotomy and may be attenuated by therapeutic antagonism.

Experimental Adhesion Model: Effect of Viscosities of Fluids Put in the Peritoneal Cavity on Preventing Peritoneal Adhesions

In this study we assessed the effectiveness of fluid viscosities placed in the peritoneal cavity to prevent postoperative peritoneal adhesions. Thirty-six Wistar albino female rats (average weight: 160 +/- 30 g, average age: 6.5 months) were divided into three groups of equal number. A standard adhesion pattern was formed in each group. Then, 3 ml isotonic sodium chloride solution (relative viscosity value: 1) was added into the peritoneal cavity of group 1; 3 ml standard 6% hydroxy ethyl starch solution (HES) (relative viscosity value: 2.9) was added into the peritoneal cavity of group 2; and a standard HES solution that was concentrated by dehydration (relative viscosity value: 249.7) was added into the peritoneal cavity of group 3. All rats were sacrificed on postoperative day 10 and the adhesions that formed were graded. In group 1, grade-3 adhesions developed in 9 (75%) rats, and grade-2 developed in 3 (25%) rats. In group 2, grade-3 adhesions developed in 1 (8.3%) rat, grade-2 developed in 6 (50%) rats, and grade-1 developed in 5 (41.6%) rats; in group 3, grade-3 adhesions developed in 9 (75%) rats, and grade-2 developed in 3 (25%) rats. The adhesion scores of group 3 and group 1 were equal to each other (P=1), while the adhesion score of group 2 was significantly less (chi(2): 18.23, P<0.001). Increasing the viscosity of fluids that are inserted in the peritoneal cavity may reduce the formation of postoperative peritoneal adhesions till a critical value of unknown viscosity is achieved. The mechanism behind this process remains unclear.

Evaluation of topical application of honey in prevention of post-operative peritoneal adhesion formation in dogs

*Summary The objective of this study was to determine the effectiveness of topical administration of honey in prevention of or reduction in post-surgical peritoneal adhesions in dog. The study was conducted on 18 adult female mixed-breed dogs with a mean ± SD weight of 20 ± 4.25 kg. A standardized surgical trauma (serosal trauma model) was made in the dogs’ descending colon to induce adhesion formation. The control group (n = 9) received saline treatment. In the experiment group (n = 9), the lesions were covered with honey. Three weeks after laparotomy, the dogs were sacrificed and the adhesions were graded according to the Evans’s scoring system. Overall, 67% (n = 6) of the control and 22% (n = 2) of the experiment animals presented with moderate (grade-2) and severe (grade-3) adhesions. In the control group, there were 3 (33%) dogs with grade-0 or grade-1 adhesions, while in the experiment group there were 7 (78%) dogs with the same grades of adhesions. The difference between the two groups was significant (P<0.05). It was concluded that honey is a useful covering for damaged peritoneal surfaces and has high effectiveness in reducing post-operative adhesions.

Novel Role for Mast Cells in Omental Tissue Remodeling and Cell Recruitment in Experimental Peritoneal Dialysis

Because of its dynamic structure, the omentum plays a key role in the immunity of the peritoneal cavity by orchestrating peritoneal cell recruitment. Because mast cells accumulate in the omentum upon experimental peritoneal dialysis (PD) and may produce angiogenic/profibrotic factors, it was hypothesized that mast cells mediate omental tissue remodeling during PD. Daily treatment with conventional PD fluid (PDF) for 5 wk resulted in a strong omental remodeling response, characterized by an approximately 10-fold increase in mast cell density (P < 0.01), an approximately 20-fold increase in vessel density (P < 0.02), an approximately 20-fold increase in the number of milky spots (P < 0.01), and a four-fold increase in submesothelial matrix thickness (P < 0.0003) in wild-type rats. In contrast, all PDF-induced omental changes were significantly reduced in mast cell-deficient Ws/Ws rats or in wild-type rats that were treated orally with a mast cell stabilizer cromoglycate. A time-course experiment showed mast cell accumulation immediately before the formation of blood vessels and milky spots. Functionally, PDF evoked a peritoneal cell influx, which was significantly reduced in Ws/Ws rats (P < 0.04) and in wild-type rats that were treated with cromoglycate (P < 0.03). Cromoglycate treatment also completely prevented PDF-induced omental adhesions to the catheter tip (P = 0.0002). Mesothelial damage, angiogenesis, and fibrosis of mesentery and parietal peritoneum as well as glucose absorption rate and ultrafiltration capacity proved to be mast cell independent. Data strongly support the hypothesis that mast cells mediate PDF-induced omental tissue remodeling and, subsequently, peritoneal cell influx and adhesion formation, providing therapeutic possibilities of modulating omental function.

Peritoneal Fibrinolytic Response to Various Aspects of Laparoscopic Surgery: A Randomized Trial

Peritoneal fibrinolysis is important in peritoneal wound healing processes and adhesion formation. The peritoneal fibrinolytic response to laparoscopy is merely unknown. In the present study we investigate the effect of short-term laparoscopy on the peritoneal fibrinolytic response and the influence of intra-abdominal pressure, light intensity and choice of dissection device on this response. There were 50 patients scheduled for laparoscopic cholecystectomy randomized in five groups operated with various pressures, light intensities, and dissection devices. Peritoneal biopsies were taken at the beginning and the end of the procedure. Tissue concentrations of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1), and the tPA-activity were measured using ELISA techniques. There were no differences in tPA antigen, tPA-activity, uPA antigen, or PAI-1 antigen concentrations in biopsies taken at the beginning compared to samples taken at the end of the operation. Different intra-abdominal pressures, light intensities and the choice dissection device did not affect any of the measured parameters. Short-term laparoscopy does not affect the peritoneal fibrinolytic activity. The used intra-abdominal pressure, light intensity and choice of dissection device do not affect peritoneal activity during short-term laparoscopy.

Sildenafil reduces postoperative adhesion formation in a rat uterine horn model

Objective The purpose of this experimental study was to evaluate the effect of oral sildenafil on postoperative adhesion formation in rats. Study design Thirty-two Wistar Albino rats were subjected to standardized lesion by cauterization of the uterine horn and abrasion of the adjacent parietal peritoneum. They were randomized to receive sildenafil at a daily dose of 15 mg/kg, 7.5 mg/kg and 3.75 mg/kg or placebo. Sildenafil was administered by gavage 1 h before the operation and daily for 5 days after the procedure. The extent and severity of adhesions were assessed on the 14th postoperative day. Result(s) The severity but not extent of adhesions in rats given 15 mg/kg sildenafil was significantly less when compared with the other groups (<0.001). Conclusion Sildenafil diminishes peritoneal adhesion formation in rat.

Angiogenic factors in peritoneal adhesion formation

Abdominal surgery is considered as the leading cause of peritoneal adhesions and almost universally as adhesiogenic. Peritoneal injury at the time of surgery initiates an inflammatory reaction determining fibrin deposition on the wound surface. Depending on the balance between the different components of the plasminogen system, this fibrin can be either lysed, leading to normal peritoneal healing, or organised, serving as a scaffold for fibroblast ingrowth, extracellular matrix deposition and angiogenesis, leading to adhesion formation. The mechanism underlying the predisposition to form adhesions in some patients and in some specific anatomic sites and not in others after similar surgical procedures remains unknown. In spite of the many attempts proposed over the years for reducing the incidence of adhesion formation, peritoneal adhesions remain a major clinical problem, inducing intestinal obstruction, pelvic pain, female infertility and difficulties at the time of re-operation. The available evidence indicates that understanding the adhesion formation process at the molecular level is essential for developing successful strategies for preventing adhesions. Fortunately, the advancement in molecular biology during the last years has led to the identification of many molecules with the potential of regulating inflammatory and immune responses, tissue remodelling and angiogenesis, key events in peritoneal healing and adhesion formation. This review focuses on the role of angiogenesis and angiogenic factors in peritoneal adhesion formation.

Time to reconsider saline as the ideal rinsing solution during abdominal surgery

Background Peritoneal mesothelial cells lining the peritoneal cavity play a primary role in prevention of formation of peritoneal adhesions, which depends mainly on their fibrinolytic activity. During surgical procedures, the abdominal cavity is in most cases rinsed with normal saline solution, which may modify the fibrinolytic activity of the peritoneal mesothelium and predispose to formation of adhesions. The goal of our experiments was to evaluate how normal saline and other solutions affect the fibrinolytic properties of the peritoneal mesothelial cells. Material and methods Experiments were performed on in vitro cultures of human peritoneal mesothelial cells. Mesothelial monolayers were exposed during 6 hours to the following solutions: culture medium (control), .9% NaCl, Hanks solution, Earles solution, new peritoneal dialysis fluid with low glucose degradation products (GDP) concentration (PDF), and peritoneal dialysis fluid with high concentration of GDP (PDF-GDP). Afterwards, morphology of the cells as well as leakage of lactate dehydrogenase (LDH) from their cytosol were evaluated. During the next 24 hours when the cells were cultured in standard medium synthesis of interleukin-6 (IL-6), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were studied. Results Mesothelial monolayers exposed to .9% NaCl or to PDF-GDP showed destruction of their morphology after 6 hours incubation and in case of PDF-GDP release of LDH from the cytosol was increased by 275% versus the control ( P < .05). During subsequent culture of all cells in standard medium, the release of IL-6 was decreased in cases of cells pretreated with .9% NaCl (−58%, P < .05) or PDF-GDP (−93%, P < .001). The release of t-PA was also reduced from cells pretreated with .9% NaCl (−71%, P < .01) or with PDF-GDP (−74%, P < .01) but increased after exposure of these cells to PDF (+35%, P < .05). Statistically significant decrease of PAI-1 synthesis was observed in cells preexposed to .9% NaCl (−69%, P < .01) or to PDF-GDP (−82%, P < .05). When changes in the PAI-1/t-PA ratio were calculated, a strong tendency for increase of that value was seen in cells pretreated with .9% NaCl or Earles salts solution but not with PDF. However, in cases of Hanks solution, a significant increase in the PAI-1/t-PA ratio was observed (+104%, P < .01). Conclusion Exposure of the peritoneal mesothelial cells to .9% NaCl, Hanks, Earles salts solution, or PDF-GDP results either in reduction of their viability or in loss of their fibrinolytic activity. Peritoneal dialysis fluid with a low content of glucose degradation products appears to be the optimal solution causing the least damage to mesothelial cells and therefore may be the ideal solution for rinsing the abdominal cavity with low risk of inducing deterioration of the mesothelial cells fibrinolytic activity and formation of adhesions. We postulate therefore that such hypertonic peritoneal dialysis fluids should be used not only during peritoneal dialysis but also for rinsing the abdominal cavity during any surgical procedures.

Adenoviral-mediated gene expression of hepatocyte growth factor prevents postoperative peritoneal adhesion in a rat model

Mesothelial cell proliferation and migration play important roles in reducing formation of postoperative peritoneal adhesions. Hepatocyte growth factor (HGF) is a multifunctional cytokine that stimulates proliferation and migration of various cell types, including mesothelial cells. We investigated the effect of adenovirus-mediated HGF gene expression on the proliferation and migration of mesothelial cells and evaluated its preventive effects on postoperative formation of peritoneal adhesions. Rat mesothelial cells were isolated and characterized by expression of cytokeratin and vimentin. Immunohistochemical staining showed that these cells expressed c-Met, the receptor for HGF. Adenoviral-mediated HGF gene transfer into mesothelial cells resulted in high expression of HGF and enhanced migration. To evaluate the preventive effects of adenoviral-mediated HGF gene transfer on the formation of postoperative peritoneal adhesion, we employed a rat model of cecum abrasion-induced adhesion formation in which 80% of the rats developed postoperative peritoneal adhesions. Local application of recombinant adenovirus carrying the HGF gene reduced adhesion formation in 16 of 20 control rats compared with 7 of 20 treated rats in this model. These results suggest that adenoviral-mediated HGF gene transfer may be a novel strategy for preventing postoperative peritoneal adhesions.

Transplantation of an Autologous Mesothelial Cell Sheet Prepared from Tunica Vaginalis Prevents Post-Operative Adhesions in a Canine Model

Post-operative adhesions often cause severe complications such as bowel obstruction and abdominopelvic pain. Previously, we reported that transplantation of a mesothelial cell sheet is effective for preventing adhesion in rat model. We also proposed a new technique for harvesting autologous mesothelial cells from tunica vaginalis without intra-abdominal maneuvers. In this study, we examined whether an autologous mesothelial cell sheet can prevent post-operative peritoneal adhesions in a canine adhesion model. Mesothelial cells were isolated from the tunica vaginalis of male beagles. Isolated cells were cultured on fibrin gel. We named this construct the "mesothelial cell sheet." Animals underwent surgery to induce peritoneal adhesion formation and were then transplanted with the mesothelial cell sheets (sheet group, n = 4), fibrin gel (fibrin group, n = 4), or no materials (sham group, n = 4). Four weeks after the transplantation, we evaluated adhesion formation and scored adhesion levels. The abdominal wall transplanted with the mesothelial cell sheet was covered with mesothelium. The total adhesion score of the sheet group was significantly lower than that of the fibrin group and the sham group. These results indicated that transplantation of an autologous mesothelial cell sheet is effective for preventing post-operative adhesion formation in the canine adhesion model. Our mesothelial cell sheet has the potential to be a powerful adhesion prophylactic material in surgery.

Response of human peritoneal mesothelial cells to inflammatory injury is regulated by interleukin‐1b and tumor necrosis factor‐a

Peritoneal injury is often associated with alterations of the mesothelium, resulting in peritoneal healing and adhesion formation. We analyzed the effects of pro-inflammatory cytokines on cell morphology and proliferation of human peritoneal mesothelial cells (HPMC). After 48 hours, HPMC formed a confluent layer with cell volumes of 2,662+/-111 fL. Treatment of HPMC with interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) induced mesothelial disintegration and alterations in mesothelial cell morphology, which were associated with an interleukin-1beta-triggered increase in cell volume (3,028+/-118 fL; p<0.05) and exfoliation of cells into the supernatants of cell cultures (p<0.05). Whereas TNF-alpha arrested HPMC in the G0/G1 phase (p<0.05), interleukin-1beta caused an increase of cells into the S phase of the cell cycle. In addition, interleukin-1beta and interferon-gamma exerted a proliferative effect on HPMC. These changes were independent from mesothelial Na+/H+ antiporter-1 expression. Our data indicate that the response of HPMC to inflammatory injury is regulated by interleukin-1beta and TNF-alpha reflecting their putative role in peritoneal wound healing and adhesion formation.

A neurokinin‐1 receptor antagonist (NK‐1RA) that reduces postoperative adhesions decreases markers of oxidative stress in the peritoneum

Postoperative oxidative stress may contribute to peritoneal adhesion formation. Substance P is known to increase reactive oxygen species (ROS) in inflamed tissues by binding the NK-1 receptor. We recently demonstrated in rats that a NK-1RA reduced adhesion formation. The aim of this study was to determine if administration of the NK-1RA affects oxidative stress in the postoperative peritoneum. Methods Adhesions were surgically induced in rats that received the NK-1RA (CJ-12,255, Pfizer) or vehicle. Peritoneal tissue was isolated at 1 and 7 days (D) for analysis of biomarkers of oxidative stress including 8-isoprostanes (8-IP), protein carbonyls, NADPH oxidase (NOX), myeloperoxidase (MPO) and ICAM-1 and VCAM-1 mRNA. Results Compared to non-operated control levels, 8-IP, NOX, MPO and VCAM-1 mRNA were elevated at 1 and 7 D. ICAM-1 mRNA was increased at 7 D and protein carbonyl did not change. The NK-1RA reduced 8-IP levels at 1 D, ICAM-1 mRNA at 7 D and protein carbonyl at 1 and 7 D, with no effect on NOX, MPO or VCAM-1 mRNA (Table). Conclusion These data suggest that oxidative stress may play a role in adhesion formation and that the NK-1RA may reduce adhesions, in part, by decreasing ROS in the postoperative peritoneum.

Pentoxifylline, a Methyl Xanthine Derivative, Reduces Peritoneal Adhesions and Increases Peritoneal Fibrinolysis in Rats

Peritoneum has an intrinsic fibrinolytic activity that breaks the peritoneal adhesions. Peritoneal injuries with ischemia interfere this fibrinolytic activity and cause adhesions. Pentoxifylline, a methyl xanthine derivative, improves blood flow by decreasing its viscosity and also increases fibrinolytic activity in plasma. We hypothesized that pentoxifylline would increase peritoneal fibrinolysis and ameliorate adhesions. A rat model of peritoneal adhesion (cecal abrasion with gauze, n = 15 for each group) was used to test this hypothesis and cardinal parameters of peritoneal fibrinolysis were measured in peritoneal samples. No medication was given in control animals, while pentoxifylline was administered intraperitonealy (IP) (25 mg/kg, before abdominal closure to whole abdomen) or intravenously (IV) (25 mg/kg, for 9 days after operation) in the experimental groups. At postoperative day 10, peritoneal biopsies were obtained and adhesions were graded qualitatively. Activities and concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), tPA/PAI-1 complex and hydroxyproline contents were determined. Total adhesion scores were decreased in both treated groups. Mean levels of tPA concentration and tPA activity were increased in the treated groups compared to controls (p < 0.001 and p = 0.001, respectively). The tPA/PAI-1 complex levels were similar among the three groups. PAI-1 levels were lower in animals receiving IP pentoxifylline compared to control animals and those treated with IV pentoxifylline (p = 0.048, p = 0.015, respectively). Peritoneal hydroxyproline levels were similar among the three groups. Our results suggest that pentoxifylline administration either through IV or IP may reduce peritoneal adhesion formation probably by altering peritoneal fibrinolytic activity.

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.

The effect of postoperative peritoneal lavage on survival, peritoneal wound healing and adhesion formation following fecal peritonitis: an experimental study in the rat.

Abstract The effect of postoperative peritoneal lavage on survival, peritoneal wound healing and adhesion formation has been studied in rats both with and without fecal peritonitis. Peritoneal lavage with both Hartmann's solution and noxytiolin through an indwelling peritoneal cannula resulted in a delay in peritoneal wound healing in the absence of fecal peritonitis. There was also an increase in the incidence of adhesions. Induction of a fecal peritonitis followed by operation 2½–3 hours later resulted in 100 per cent mortality within 24 hours. This mortality was reduced by 66 per cent following peritoneal lavage with Hartmann's solution alone, although this resulted in a delay in peritoneal wound healing. Peritoneal lavage with noxytiolin did not reduce the mortality rate.

Noxythiolin (Noxyflex), aprotinin (Trasylol) and peritoneal adhesion formation: An experimental study in the rat

Clinical and experimental studies have suggested that noxythiolin and aprotinin may prevent intraperitoneal adhesion formation. A comparison was therefore made of their efficacy in preventing the reformation of adhesions following surgical lysis in a controlled trial using rats. Neither noxythiolon nor aprotinin had any significant benefit over surgical lysis alone. The mortality rate was high in the noxythiolin-treated group.

The effect of tetracycline lavage and trauma on visceral and parietal peritoneal ultrastructure and adhesion formation.

The clinical efficacy of tetracycline lavage (1 mg/ml) in the management of abdominal sepsis has led to advocacy of its use in potentially contaminated cases. Yet at higher concentrations (6 mg/ml), tetracycline is a pleural sclerosant. The possibility of early ultrastructural peritoneal damage and later adhesion formation has been examined in syngeneic female Wag rats. At high concentration (10 mg/ml), tetracycline caused adhesions in the absence of peritoneal trauma and there was an associated loss of serosal microvilli. Lavage with low concentration tetracycline (1 mg/ml) or saline after clean abdominal surgery led to more adhesions than if no lavage was employed. There was an unexplained paradoxically low incidence of adhesions if prior mild contamination of the peritoneal cavity with 1 ml 10(5) E. coli had been performed.

Development of Peritoneal Adhesions in Macrophage Depleted Mice

We present a new mouse model for the study of peritoneal adhesions using macrophage Fas-induced apoptosis (Mafia) transgenic mice expressing a Fas-FKBP construct under control of the murine c-fms promoter. Mafia mice allow systemic macrophage depletion by dimerization of Fas with a synthetic dimerizer, AP20187. Results demonstrate that macrophage depletion in Mafia mice induces peritoneal adhesion formation when the peritoneal cavity is also exposed to an irritant. The Mafia mouse model presents a reproducible, non-surgical approach for research in adhesion formation and prevention. Mafia mice were treated with AP20187 using an intravenous (i.v.) or intraperitoneal (i.p.) injection. Control groups included mock-treated Mafia mice and both AP20187 and mock-treated wild type mice. Seven days after treatment, mice were observed for the presence of adhesions. After i.p. injection with AP20187, 76% of Mafia mice developed adhesions whereas none of the mock-treated Mafia or wild-type mice developed adhesions, and only one AP20187-treated wild-type mouse (5.8%) developed a mild adhesion. Mafia mice treated with AP20187 i.v. exhibited macrophage depletion not significantly different than i.p. treated mice, but did not develop adhesions. In contrast, Mafia mice treated with AP20187 i.v. developed adhesions when diluent was also injected into the peritoneal cavity, whereas i.p diluent alone had no effect. Macrophage depletion, combined with a peritoneal irritant, results in peritoneal adhesion formation in transgenic Mafia mice. Macrophages appear to play a protective role in the development and/or repair of peritoneal adhesions.

Coincidence of Connective Tissue Growth Factor Expression with Fibrosis and Angiogenesis in Postoperative Peritoneal Adhesion Formation

Purpose: To investigate the relationship between connective tissue growth factor (CTGF) and fibrosis and angiogenesis in postoperative peritoneal adhesion formation. Methods: Adhesions were performed in 35 rats by creation of a peritoneal patch. Animals were sacrificed at 7 different time-points over 3 weeks. Adhesions and uninjured peritoneum from all animals were assessed by Northern blotting for CTGF and collagen-I mRNA and by immunohistochemistry for CTGF localization, degree of fibrosis and angiogenesis. Results: Persistent adhesions formed in all animals. CTGF and collagen-I mRNA were increased in adhesions compared to uninjured peritoneum (p < 0.05 for both). The temporal expression pattern depicted delayed peak levels of collagen-I mRNA with increasing tendency for both transcripts at the end of the observation period. Fibrosis within adhesions correlated positively with time after surgery (r = 0.85; p < 0.001) and showed typical signs of chronic tissue fibrosis at later time points. Angiogenesis was detected in adhesions but not in uninjured peritoneum (p = 0.001) and coincided with the spatial and temporal expression of CTGF protein in fibroblasts and vascular endothelial cells. Conclusions: The co-expression of CTGF with increasing fibrosis and angiogenesis in postoperative peritoneal adhesions suggests a role for CTGF as critical molecule in fibrous adhesive disease and target for future adhesion prevention.

Is Normal Saline Harmful to the Peritoneum?

Normal saline (0.9% NaCl) is used during various abdominal surgical interventions and during peritoneal dialysis to rinse the peritoneal cavity. Although no clear clinical evidence exists for the bioincompatibility of normal saline, various experimental studies have suggested that 0.9% NaCl solution can initiate fibrosis of peritoneum. We review the data derived from in vitro and in vivo experimental studies demonstrating the cytotoxic effect of 0.9% NaCl and its ability to initiate peritoneal adhesions. Normal saline reduces the viability and fibrinolytic activity of peritoneal mesothelial cells. Use of normal saline to wash the peritoneal cavity during abdominal operations or after chronic peritoneal dialysis is more likely to produce adhesions than is no irrigation at all. Chronic exposure of the peritoneum to normal saline causes overgrowth of the connective tissue and formation of new blood vessels within that tissue. Normal saline is a bioincompatible solution that predisposes to the formation of peritoneal adhesions and fibrosis of the peritoneum. A 0.9% NaCl solution should therefore not be used to rinse the peritoneal cavity after interruption of peritoneal dialysis.