Development of peritoneal adhesions in macrophage depleted mice

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Phosphatidylcholine prevents postoperative peritoneal adhesions: an experimental study in the rat

Phosphatidylcholine (PC) is the main constituent of the surface-active material coating peritoneal mesothelium. It may prevent postoperative adhesion formation through production of a lubricant film on mesothelial defects. We therefore examined the effect of its soluble form on surgically induced intraabdominal adhesions in rats. The adhesions were induced at laparotomy by any of four different operative models. PC was administered intraperitoneally (20 mg/rat) or intravenously (20 mg/rat or 50 mg/rat) at the end of the operation and on the second and third postoperative day. It was found that the degree of postoperative adhesion formation was significantly reduced by the intraperitoneal injection of PC in all 4 models. In contrast, no effect was achieved by the intravenous injection of PC, not even at a very high dose level. Our results suggest that soluble PC administered intraperitoneally might be a potent adjunct in postoperative adhesion prevention.     

Role of aminophylline and allopurinol in the reformation of peritoneal adhesions

The role of aminophylline in the re-formation of peritoneal adhesions was considered in 23 rats. Since the adhesions were obtained, the animals were subsequently divided into three groups, the first one containing seven units, the others containing eight animals each. During the four days prior the surgery, allopurinol at the dose of 50 mg/kg/die was added to the regular ground laboratory chow in the animals of the second group; aminophylline at the dose of 40 mg/kg/die was administered four hours and immediately prior the surgery, to the animals of the third group. The adhesions that we observed, were graded and evaluated assigning them a score. At the moment of the lysis of adhesions, we observed the score of 2.71 +/- 1.11 in the first group, 3.12 +/- 1.13 in the second group, and 2.75 +/- 1.03 in the third one. Matching each group one another no statistically significant difference was found. At the end the experiment, we observed a score of 3.71 +/- 0.49 for the adhesions in the first group, 2 +/- 0.75 in the second group, and 3.87 +/- 0.35 in the third one. Matching these scores with those observed at the moment of their lysis, they appeared significantly higher in the animals of the first group (p less than 0.02) and of the third group (p less than 0.05), but they were lower in the second group (p less than 0.05). Such results indicate that the re-formation of peritoneal adhesions following their lysis is constant, that allopurinol decreases the intensity of the process, while aminophylline increases it.     

In situ cross-linkable hyaluronan hydrogels containing polymeric nanoparticles for preventing postsurgical adhesions

OBJECTIVE: To develop a combined barrier method and drug delivery system ("hybrid system") for preventing postoperative peritoneal adhesions, which could combine the biocompatibility and ease of application of in situ cross-linkable hydrogels with the controlled release features of polymeric nanoparticles. METHODS: Poly(lactic-co-glycolic acid) nanoparticles were dispersed in aldehyde- and hydrazide-modified hyaluronic acids (HA), then combined via a double-barreled syringe. The material was subjected to mechanical testing and was assayed for in vitro cytotoxicity to murine mesothelial cells. Subsequently, it was tested for biocompatibility by intraperitoneal injection in mice. The hybrid's effectiveness in preventing postsurgical adhesions was assessed using a rabbit sidewall defect-cecum abrasion model, where it was applied to both injured surfaces. RESULTS: The in situ hybrid gel system formed a flexible and durable hydrogel in less than 10 seconds. It had low in vitro cytotoxicity. In the mouse, the cross-linked HA maintained the polymeric nanoparticles in the peritoneum for 1 week, which we had previously shown would have cleared in less than 2 days, and no animals developed adhesions. Notably, the hybrid gel, even in the absence of encapsulated drug, was highly effective in preventing peritoneal adhesions in the rabbit model employed. Animals treated with the hybrid (n = 8) had no adhesions in 62.5% of cases, and none had adhesions that could only be separated by sharp dissection. In contrast, only 4.2% of untreated animals (n = 24) had no adhesions, and 58.3% developed adhesions requiring sharp dissection. CONCLUSIONS: The hybrid cross-linked HA-nanoparticle system described here appears to be a biocompatible and highly effective adhesion barrier, which could also deliver antiadhesion drugs.     

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.     

The role of feces, necrotic tissue, and various blocking agents in the prevention of adhesions.

Ischemic tissue and intraperitoneal bacteria have been ascribed an etiologic role in the production of intra-abdominal adhesions. To further elucidate the role of these stimuli and to evaluate the potential protective effect of various agents, peritonitis was induced in 160 Sprague-Dawley rats. The experiment was stratified into those animals with peritonitis plus necrotic tissue, solid feces, both, or neither. The agents tested were a nonsteroidal anti-inflammatory (ibuprofen), free radical scavenger (SOD), and an anticoagulant (heparin). Death was less likely to occur in animals treated with heparin (3 of 40 vs. 12 of 40, p less than 0.01) or SOD (4 of 40 vs. 12 of 40, p less than 0.05). Ibuprofen did not increase survival in this model. Heparin protected against adhesions in animals with an ischemic ileum of limb and without solid feces. In animals with a nonischemic isolated segment of ileum and solid feces, adhesion formation was increased in both the ibuprofen and the heparin treatment groups (p less than 0.05).     

Modulation of the macrophage respiratory burst by an acidic environment: the critical role of cytoplasmic pH regulation by proton extrusion pumps

Within the acidic milieu of an abscess or tumor, macrophages must be able to maintain their cytoplasmic pH (pHi) close to the physiologic range to ensure optimal cell function. Our recent studies have demonstrated that a proton-extrusion mechanism with the characteristics of an H+ adenosine triphosphatase mediates pHi recovery in acid-loaded macrophages. These studies were designed to examine the role of these H+ pumps in maintaining cell function in an acidic extracellular environment. Peritoneal macrophages were tested for superoxide production in response to phorbol myristate acetate at either physiologic or acidic extracellular pH (pHo; 7.35 or 6.70, respectively). pHi was measured with the fluorescent dye 2',7'-biscarboxy-ethyl-5(6)-carboxy-fluorescein. Bafilomycin A1, a specific H+ adenosine triphosphatase inhibitor, was used to examine the contribution of the H+ pump to pHi regulation and cell function. At pHo 7.35, bafilomycin A1 had no effect on pHi or phorbol myristate acetate-stimulated superoxide production. However, at pHo 6.70, bafilomycin A1 reduced pHi to 6.61 +/- 0.01 versus 6.79 +/- 0.01 in control cells (p less than 0.001) and caused a concomitant reduction in superoxide production to 4.8 +/- 1.2 versus 13.0 +/- 1.2 nmol/10(6) cells/40 min in control cells (p less than 0.001). To determine whether the observed reduction in superoxide formation was the result of the pHi reduction, superoxide production was measured in cells whose pHi was pharmacologically clamped at various levels according to the K+/nigericin method. Lowering pHi from 6.80 to 6.60 caused a significant reduction in superoxide production from 13.1 +/- 1.8 to 7.5 +/- 0.9 nmol/10(6) cells/40 min (p less than 0.01). Thus H+ extrusion pumps are important to maintenance of macrophage pHi at low pHo, permitting continued superoxide production under these conditions. By keeping pHi close to the physiologic range, these pumps serve to optimize cell function in an acidic extracellular environment.     

1,25-Dihydroxycholecalciferol and peritoneal macrophage chemotaxis in patients on continuous ambulatory peritoneal dialysis.

Single graded doses of 1,25-dihydroxycholecalciferol of 2 and 4 micrograms were added intraperitoneally into the overnight 1.5% glucose dialysate of 6 patients on continuous ambulatory peritoneal dialysis. The effect on peritoneal macrophage chemotaxis and random migration was studied and compared with the baseline when no 1,25-(OH)2D3 was added. No consistent effect on peritoneal macrophage chemotaxis was observed. Random migration was significantly depressed at 4 micrograms when compared with baseline (5.4 +/- 1.9 vs. 12.2 +/- 3.7 cells/high-power field, p less than 0.05). The potential clinical role of 1,25-(OH)2D3 as an immune modulator requires further study.     

Quantitative peritoneal lavage in the assessment of intraperitoneal inflammatory processes

Quantitative peritoneal lavage in order to assess the volume of the intraperitoneal fluid was performed in 34 female patients with acute abdominal pain and signs of peritoneal irritation. The peritoneal lavage was done using the dye-dilution technique with Evans-Blue Human Serum Albumin Complex (EBA) as a marker. In 22 patients with intraperitoneal inflammatory process the mean volume of exudate in the peritoneal cavity was 585.1 ml while in patients without any intraperitoneal inflammatory process the mean volume of the intraperitoneal fluid was 128.7 ml. This difference between the volumes was statistically significant (p less than 0.05). It is felt that an intraperitoneal fluid volume of above 250 ml is a highly suggestive indicator of an intraperitoneal inflammatory process. A quantitative peritoneal lavage with EBA as a marker can therefore be used as a diagnostic tool in the evaluation of patients with acute abdominal pain.     

Effect of intraperitoneal administration of oxygen on the course of experimentally induced peritonitis

Over the first 3 days of experimentally induced peritonitis, 40 rabbits were given oxygen intraperitoneally (IP) up to a pressure of 3 to 5 mm Hg in the peritoneal cavity at 12-hour intervals. Compared with a control group, significant differences were recorded in the mortality rate within the studied 7-day period of peritonitis (p less than 0.05). In 29 rabbits with intraperitoneal administration of oxygen, the size of the area that formed the inner wall of the abscess cavity was significantly smaller (p less than 0.01) on day 7 of peritonitis than in the control group. The number of samples obtained from the abscesses positive for Clostridium perfringens (p less than 0.05) and for Staphylococcus aureus (p less than 0.001) was significantly lower in rabbits that had received intraperitoneal oxygen than in the control group. The number of samples from the abscesses positive for Escherichia coli and Streptococcus faecalis was significantly lower in the control group than in the group with intraperitoneal administration of oxygen (p less than 0.05). These results indicate that intraperitoneal administration of oxygen has an effect on the mortality rate associated with peritonitis, the size of the intraperitoneal abscess, and the bacterial composition of these abscesses.     

Indomethacin decreases carrageenan-induced peritoneal adhesions

For evaluation of a rat intra-abdominal adhesion model, 48 study rats were each given an intraperitoneal injection of 1 ml of 1.5% carrageenan solution and 48 control rats were each given 1 ml of sterile saline solution. Thereafter, 6 control and 6 study rats were killed on days 2, 3, 4, 5, 7, 9, 14, and 21 for assessment of the temporal nature of adhesion formation. No peritoneal reaction or adhesions occurred from saline solution. Carrageenan induced a generalized peritonitis between days 2 and 7. The frequency of adhesions from day 5 onward was 66%. The effects of celiotomy and of systemic indomethacin on carrageenan-induced adhesion formation were then examined. Rats underwent a standardized celiotomy and, on closure of the abdomen, received either an intraperitoneal injection of saline solution (n = 72) or an intraperitoneal injection of carrageenan solution (n = 96). Both groups were then randomized to receive either no indomethacin (IND-0), a single preoperative dose of indomethacin (IND-1), or four perioperative doses of indomethacin (IND-4). Then, 2, 5, 14, and 21 days later, rats from each group were killed, the extent of intraperitoneal adhesions was assessed, and the nature of any adhesions was histologically examined. Celiotomy plus intraperitoneal saline solution produced no adhesions. Celiotomy plus intraperitoneal carrageenan solution (IND-0) significantly increased adhesions to 83%. Preoperatively and perioperatively administered indomethacin significantly decreased the adhesion formation rate to 49%.     

Surgical glove powder and intraperitoneal adhesion formation. An appeal for the use of powder-free surgical gloves.

Intraperitoneal adhesion formation is a major cause of infertility and/or intestinal obstruction. Among the many well-known aetiological factors responsible for peritoneal inflammatory reaction is surgical glove powder; for example, cornstarch powder. A study was undertaken on 30 rats to determine whether cornstarch powder caused intraperitoneal adhesions. The rats were randomised into two groups under laboratory conditions. Laparotomies were performed on all the rats and trauma inflicted to the right uterine horn. The study group received cornstarch powder suspended in normal physiological salt solution intraperitoneally, and the control group received only normal physiological salt solution. Peritoneal adhesions were evaluated after 2 weeks and statistically analysed with a t-test and 95% confidence intervals. The study group showed a statistically significantly higher incidence of intraperitoneal adhesions (P = 0.0003). It is concluded that cornstarch, as used on surgical gloves, caused peritoneal adhesions and should therefore be removed before surgery. Powder-free gloves are more suitable for preventing adhesion formation.     

Reduction of primary postoperative adhesion formation under calcium channel blockade in the rabbit

Preliminary studies in a hamster model have demonstrated calcium channel blocking agents to be potent inhibitors of primary post-traumatic peritoneal adhesion formation. The present investigation was designed to extend these observations to an extensively studied model, the rabbit, and to evaluate the optimal route of administration of these drugs for intraabdominal surgery. Rabbits were subjected to a standardized traumatic lesion of the left uterine horn. Subsequently, animals were divided into the following treatment groups: subcutaneous vehicle control (n = 7), intraperitoneal (ip) vehicle control (n = 8), subcutaneous verapamil treatment (n = 6), low-dose (2.5 micrograms/kg/hr) ip verapamil treatment (n = 10), and high-dose ip (25 micrograms/kg/hr) verapamil treatment (n = 6). All animals were reexplored at 1 week postop for evaluation of adhesion formation (scale: 0 to 4+). Calcium channel blockade-treated animals formed significantly fewer adhesions (0.45) than controls (3.93) (P less than 0.01). There was no significant difference between animals treated with sc with verapamil sc and those treated with low- or high-dose verapamil ip (0.33 vs 0.20 vs 1.0). These data confirm our preliminary results, suggesting that calcium channel blockade potently modulates peritoneal healing and regeneration. Furthermore, intraperitoneal delivery and systemic administration appear equipotent in this model. Further study of these agents as potential adjuvants for intraperitoneal surgery is indicated.     

Noxytiolin and peritoneal adhesion formation.

Clinical and experimental studies have suggested that intraperitoneal noxytiolin prevents adhesion formation. A reliable experimental animal model was therefore established and the effect of noxytiolin on adhesion formation was evaluated in a controlled trial using 80 rats. All 40 rats given Ringer solution developed adhesions, whereas in 7 out of 40 given noxytiolin no adhesions were found (P less than 0-02). Noxytiolin reduced both the total and the mean number of adhesions formed (P less than 0-2) and their mean length of attachment (P less than 0-05). The anti-adhesive effect of noxytiolin may be due to its anticoagulant, cytotoxic or antibacterial properties.     

Reduced human peritoneal plasminogen activating activity: possible mechanism of adhesion formation

A unifying pathophysiological hypothesis states that the plasminogen activating activity (PAA) of the peritoneal mesothelium determines whether the fibrin which forms after peritoneal injury is either lysed or organized into permanent fibrous adhesions. The PAA of human peritoneal biopsies was measured using a fibrin plate lysis technique to assess the changes that occur in inflammation and ischaemia, conditions which both produce fibrous adhesions. Activity was found in all biopsies from normal parietal and visceral (appendix, bowel and omentum) peritoneum with no significant site-to-site variation. Inflamed peritoneum (parietal, appendicular and mesenteric) had significantly less PAA compared with normal peritoneum; visceral ischaemia also resulted in a significant decrease of PAA. These reductions in human peritoneal PAA observed in inflammation and ischaemia support the view that mesothelial PAA plays a key part in the prevention of events leading to the production of fibrous adhesions.     

Comparison of blood and peritoneal neutrophil activity in rabbits with and without peritonitis

The neutrophil (polymorphonuclear cell, or PMN) function is an essential component of the host defense against infection. However, infection itself may alter PMN activity. To investigate both the effects of infection on PMN activity and PMN activity on survival, we evaluated control and infected blood and peritoneal PMN phagocytosis, chemotaxis, and superoxide anion production in rabbits with and without peritonitis. Control blood and peritoneal PMNs were obtained from noninfected rabbits which were subjected to intraperitoneal infusion of sterile hypertonic saline. Infected blood and peritoneal PMNs were obtained from rabbits which had undergone appendiceal devascularization and ligation 18 hr earlier. Phagocytosis was similar in all groups except for a threefold increase in normal peritoneal PMNs. Chemotaxis was inhibited by infection in the blood and peritoneal PMNs. Normal peritoneal PMNs also had decreased chemotaxis. Superoxide anion production was comparable in the infected and control blood; however, both control and infected peritoneal PMNs had elevated superoxide anion production. Of the infected rabbits, four died in 5 days or less. Of the six that lived, two developed intraabdominal abscesses. Blood and peritoneal PMN activity was similar in all rabbits despite their outcome. We conclude that (1) blood and peritoneal PMNs have different basal activities and responses to infection; (2) the milieu of the peritoneal cavity appears to alter the PMNs present; and (3) PMN activity did not predict morbidity or mortality.     

Effects of surgical gloves on postoperative peritoneal adhesions and cytokine expression in a rat model

BACKGROUND: Postoperative intraperitoneal adhesions are a major cause of morbidity. We studied the effects of synthetic and latex gloves, and their powders, on postoperative adhesions and cytokine expression in a rat model. METHODS: Rats underwent laparotomy and cecal abrasion. Rats were grouped based on the glove type used: synthetic powder-free (SPF), synthetic powdered (SP), latex powder-free (LPF), and latex powdered (LP). Serum cytokine (tumor necrosis factor [TNF], interleukin-1 [IL-1], and IL-6) levels were measured. Animals were killed and peritoneal adhesions were graded. RESULTS: The SPF group had no adhesions. Adhesions were increased similarly in the SP and LPF groups, and further increased in the LP group. Postoperative serum cytokine levels showed a similar pattern of increases. CONCLUSIONS: The presence of latex or powder on surgical gloves promoted increased adhesions. Serum cytokine levels correlated with the degree of adhesion formation. Strategies to use latex-free, powder-free gloves and/or limit cytokine expression may decrease peritoneal adhesions in the clinical setting.     

Prevention of postoperative adhesions with the chitin derivative N-O-carboxymethylchitosan

The ideal barrier agent for the prevention of surgical adhesions has remained elusive. We have examined the ability of a new hydrogel N-O-carboxymethylchitosan, a derivative of chitin with properties similar to the extracellular matrix, to prevent adhesions when applied topically to traumatized mesothelial surfaces. In two rodent adhesion models (pericardial and peritoneal), the application of N-O-carboxymethylchitosan significantly prevented or minimized the formation of scar and fibrosis. According to a scoring system from 0 to 3 (0 = no adhesions and 3 = severe dense adhesions), control groups in each model consistently produced severe dense adhesions (2.9 +/- 0.2, 2.7 +/- 0.3). All treated groups consistently scored less than 1.0, indicating minimal or no fibrosis. The differences between the control and treated groups were statistically significant (p < 0.05). Thus, the application of N-O-carboxymethylchitosan to traumatized mesothelial surfaces may have significant potential in the prevention of postoperative adhesion formation.     

Alterations in chemotactic factor-induced responses of neutrophils and monocytes from chronic dialysis patients

Chronic renal failure patients on dialysis have an increased susceptibility to infection. Previous studies have demonstrated that these patients have a decreased in vitro neutrophil (PMN) chemotactic response and a reduction in C5a receptor availability on both PMN and monocytes. This study was designed to determine if other chemotactic factor-mediated responses of PMN and monocytes from hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients are abnormal. The responses investigated included in vitro chemotaxis, superoxide generation, H2O2 production, and myeloperoxidase (MPO) release. These studies showed that PMN from HD and CAPD patients are significantly decreased in their chemotactic response to both C5a and fMLP when compared to normal controls. The response of HD patient's PMN to C5a was decreased by an average of 55.1% (p less than 0.005) and for CAPD patients by 49.7% (p less than 0.01). Similarly, chemotactic responses to fMLP were decreased by an average of 44.7% (p less than 0.005) for HD patients and 36.3% (p less than 0.02) for CAPD patients. Superoxide anion production by PMN and monocytes from HD and CAPD patients in response to C5a and fMLP was also significantly decreased compared to controls. PMN superoxide production in response to C5a was decreased by an average of 36.5% (p less than 0.001) for HD patients and 32.0% (p less than 0.001) for CAPD patients. fMLP-stimulated production of superoxide was also decreased but to a lesser degree with a mean decrease of 18.0% (p less than 0.01) for HD patients and 24.1% decrease (p less than 0.01) for CAPD patients. This decreased responsiveness was restricted to C5a- and fMLP-stimulated superoxide production since phorbol myristate acetate (PMA)-stimulated responses were comparable to controls. A similar pattern of decreased superoxide production was found with monocytes from these patients. Comparable decreases in chemotactic factor-stimulated responses were also observed in a flow cytometric assay of H2O2 production in both PMN and monocytes and an in vitro assay of MPO release from PMN. Analysis of the binding of fluorescent C5a to PMN showed a direct correlation between decreased C5a binding and decreased O2- production and MPO release. Since all of these chemotactic factor-stimulated events are involved in the inflammatory process and the killing of microorganisms, alterations in these WBC functions in dialysis patients may contribute to their increased susceptibility to infection.     

A novel approach to reducing postoperative intraperitoneal adhesions through the inhibition of insulinlike growth factor I activity

HYPOTHESIS: Interference with insulinlike growth factor I (IGF-I) activity, both systemically and intraperitoneally, reduces postoperative intraperitoneal adhesion severity. SETTING: Experimental animal model. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Adult female rats were subjected to hypophysectomy, sham hypophysectomy (control), IGF binding protein 4 (IGFBP-4) treatment, or albumin treatment (control). All rats underwent laparotomy and uterine horn abrasion with adjacent parietal peritoneal trauma for the purpose of creating postoperative intraperitoneal adhesions. Glucocorticoids and thyroid hormone were replaced in the hypophysectomy group. On postoperative day 10, rats were weighed, subjected to phlebotomy, and killed. Postmortem laparotomies were performed and blinded observers scored uterine-peritoneal adhesions on a 0 to 3 scoring system. Plasma IGFBP-4 levels and organ weights were measured in the IGFBP-4 and albumin treatment groups. Blood samples in all rats were analyzed for IGF-I levels. RESULTS: Rats with low IGF-I levels (hypophysectomy) and inhibited IGF-I activity (IGFBP-4 treatment) formed significantly less severe adhesions than their control counterparts. As expected, rats in the hypophysectomy group displayed greater weight loss and lower plasma IGF-I levels than sham-treated rats. Rats treated with IGFBP-4 and those treated with albumin demonstrated no differences in body weight, organ weights, IGF-I levels, and IGFBP-4 levels. CONCLUSIONS: Both the reduction of systemic IGF-I levels via hypophysectomy and the inhibition of local intraperitoneal IGF-I activity via IGFBP-4 treatment resulted in diminished postoperative adhesion severity. Treatment with IGFBP-4 may play a role in postoperative adhesion prophylaxis in the future.