Attenuation of adhesion formation after cardiac surgery with a chymase inhibitor in a hamster model

OBJECTIVE: Chymase is one of the inflammatory mediators and is released from mast cells, which are closely associated with adhesion formation. Chymase also activates transforming growth factor beta1, which promotes tissue fibrosis. However, the role of chymase in cardiac adhesion formation has not yet been elucidated. We have assessed whether a specific chymase inhibitor, Suc-Val-Pro-Phe(p) (OPh)(2), prevents postoperative cardiac adhesions in hamsters. METHODS: In 66 hamsters the epicardium was abraded, and then either chymase inhibitor or placebo was injected into the left thoracic cavity, leaving the pericardium open. Cardiac chymase activity, the level of transforming growth factor beta1 in the pleural fluid, and the density of epicardial mast cells were measured 3 days postoperatively. The degree of adhesion formation was evaluated macroscopically and histologically 2 weeks postoperatively by using a grading score ranging from 0 (no adhesions) to 4 (severe adhesions). RESULTS: The cardiac chymase activity and level of transforming growth factor beta1 were lower in the chymase inhibitor-treated group compared with in the placebo-treated group (45.8 +/- 18.7 vs 79.7 +/- 13.7 microU/mg protein [P <.025] and 15.6 +/- 6.5 vs 33.2 +/- 9.8 microg/mL [P <.01], respectively). The density of mast cells was higher in the placebo-treated group, and there was suppression to 60% of this value in the chymase inhibitor-treated group. The adhesion scores were lower in the chymase inhibitor-treated group compared with in the placebo-treated group (1.3 +/- 1.3 vs 3.0 +/- 1.1, P <.01). CONCLUSION: Use of a chymase inhibitor suppresses not only cardiac chymase activity but also the level of transforming growth factor beta1, and this results in a reduction in postoperative cardiac adhesion.     

The effects of ACE inhibition on serum angiotensin II concentration following cardiac transplantation

AIMS: ANGII mediates vascular neointimal formation through smooth muscle cell stimulation and enhanced production of growth factors leading to increased arterial medial layer thickness, which is a characteristic of transplant arteriosclerosis. ACE inhibition is known to be of benefit to patients with cardiovascular risk factors. We aimed to determine the effect of ACE inhibitor therapy on ACE enzymatic activity and serum ANGII levels following cardiac transplantation. METHODS: A total of 43 serum samples from eight transplant recipients were used for analysis. Samples were taken monthly from the date of transplant for the initial 6 months. ANGII was measured using sandwich ELISA. ACE enzymatic activity was measured using spectrophotometric kinetic analysis. RESULTS: There was a significant reduction in ACE enzymatic activity among individuals treated with ACE inhibitor therapy (18.0 +/- 16.6 vs 31.8 +/- 23.4, P = .008). We found significantly higher ANGII serum levels in patients receiving ACE inhibitor therapy compared to those not (2.4 +/- 2.1 vs 8.0 +/- 7.4, P = .002). There was also a significant positive correlation between ACE enzymatic activity and ANGII serum level (coefficient 0.332, P = .03). CONCLUSIONS: Our results suggest an effective ACE independent pathway for ANGII conversion. Chymase can convert ANGI with higher affinity than ACE. Also, chymase is stored in mast cells, which infiltrate the myocardium following transplantation. This data indicate that pharmacological chymase inhibition may be a possible therapeutic strategy following transplantation.     

Chymase inhibitor,BCEAB, suppressed peritoneal adhesion formation in hamster

BACKGROUND: Mast cells are closely related to adhesion formation, while it has been unclear which factor in mast cells plays an important role in the development of adhesion formation. To clarify the role of chymase produced from mast cells in adhesion formation, we investigated the preventive effect of a specific chymase inhibitor, BCEAB, on adhesion formation in a hamster experimental model. MATERIALS AND METHODS: Hamsters were administered orally once daily with 100 mg/kg of BCEAB or placebo from the operated day to 1 week after the operation. The uterus was grasped and denuded by a swab. RESULTS: One week after the operation, the scores for adhesion formation in the chymase inhibitor-treated group were significantly decreased in comparison with those in the placebo-treated group (placebo-treated group, 2.80 +/- 0.20; chymase inhibitor-treated group 1.60 +/- 0.31: P < 0.01). The chymase activity in the injured uterus was also significantly suppressed in the chymase inhibitor-treated group (placebo-treated group, 17.3 +/- 2.69 mU/mg protein; chymase inhibitor-treated group 9.60 +/- 0.89: P < 0.05). After scraping the utelus, the level of transforming growth factor-beta in the peritoneal fluid was significantly increased in the placebo-treated group, while it was suppressed to 70% by the treatment with BCEAB. CONCLUSIONS: The specific chymase inhibitor BCEAB may be a useful drug for prevention of adhesion formation.     

Association between the expression of mast cell chymase and intraperitoneal adhesion formation in mice

BACKGROUND: Adhesion formation is a major source of postoperative morbidity and mortality. Mast cells and their major protease, chymase, have been shown to participate in the healing process as well as in tissue remodeling. We aimed to identify the role of mast cells in intraperitoneal adhesion formation and to assess whether there is an association between the expression of mast cell chymase and adhesion formation. MATERIALS AND METHODS: Both mast cell-deficient W/W(V) mice and congenic +/+ mice received a standardized lesion produced by cecal scraping and the application of 95% ethanol. Adhesions were assessed blindly 1 week later using a standardized scale. In addition, histamine content, mast cell numbers, and chymase activity in cecum as well as at the healing sites were evaluated before and 7 days after surgical injury. RESULTS: A significant reduction in adhesion formation was seen in mast cell-deficient W/W(V) mice (P < 0.05). In the normal cecum, histamine content did not significantly differ between W/W(V) and +/+ mice. Chymase activity in cecum was detected in control +/+ mice, but not in W/W(V) mice. Mast cell numbers and chymase activity levels at the healing sites of +/+ mice were significantly increased 7 days after surgery. CONCLUSIONS: Our results indicate that mast cells contribute to intraperitoneal adhesion formation in mice, and suggest that chymase originating from mast cells is important in the development of adhesions.     

Long-term evaluation of laser-treated silicone (LTS) membrane as a pericardial substitute: in vivo study

OBJECTIVE: The purpose of this study was prevention of adhesion formation in reoperative cardiac surgery using laser-treated silicone (LTS) membrane as a new pericardial substitute in the sheep model. METHODS: Thirty ewes (35-45 kg) were used and categorized into two groups including test and control groups. In test group (n = 18), the pericardium was excised, and the LTS membrane was implanted as a pericardial substitute. In the control group (n = 12), the pericardium was excised without LTS membrane implantation. During follow-up ranging from 3 to 28 months, animals were observed for any clinical sign of postoperative problems. Thirty reoperations were performed in both test and control groups to evaluate adhesion formation. RESULTS: In the control group, dense adhesions were observed, while in the study group adhesion formation was reduced at all sites covered by LTS membrane (p < 0.03), and no infection or other complications were observed. CONCLUSIONS: The LTS membrane is safe and efficacious in the reduction of pericardial adhesion formation and might be used in patients undergoing cardiac surgery who need reoperation.     

Repeat sternotomy after reconstruction of the pericardial sac with glutaraldehyde-preserved equine pericardium

The risk of repeat sternotomy is higher than that of the initial sternotomy, especially if the pericardial sac was left open at the first intervention. In 200 consecutive patients with a pericardial defect after open heart operations, the pericardium was closed with a glutaraldehyde-preserved equine pericardial patch. Precardiac adhesions at reoperation were assessed in four groups of patients on a scale of 6, ranging from 0 (no adhesions) to 5 (calcified or ossified adhesions). Group I comprised 13 patients in whom the pericardium was left open at the first operation and an equine pericardial patch was implanted at reoperation. Group Ia included the first five Group I patients who underwent reoperation less than 1 year (early reoperation) after the initial procedure. Group Ib included the other eight patients of Group I, who underwent reoperation more than 1 year (late reoperation) after the first procedure. Group II comprised nine patients who were reoperated on after reconstruction of the pericardial sac with a glutaraldehyde-preserved equine pericardial patch. After a mean follow-up of 20.2 months, the incidence of patch-related complications was 1%. Statistical analysis shows less severe adhesions on reoperation in Group II patients (pericardial defect patched) than in Group I patients (pericardial defect left open): mean grade of adhesions 1.6 +/- 0.9 (Group II) versus 3.2 +/- 0.6 (Group I), p less than 0.001. Precardial adhesions with the pericardium left open were similar in patients having early and late reoperations: mean grade of adhesions 3.0 +/- 0.7 (Group Ia) versus 3.4 +/- 0.5 (Group Ib), no significant difference. Therefore, the glutaraldehyde-preserved equine pericardial patch can be considered a suitable material for primary closure of the pericardial sac in patients with inadequate autologous pericardium.     

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.     

Role of mast cells and myofibroblasts in human peritoneal adhesion formation

OBJECTIVE: To study fibroblasts and mast cells in human peritoneal adhesions and to evaluate whether their interaction plays a role in adhesion development. SUMMARY BACKGROUND DATA: Myofibroblasts play a critical role in wound repair/fibrosis. Mast cells influence the formation of peritoneal adhesions in a rat model, and they are modulators of fibroblast functions. METHODS: Peritoneal adhesion biopsies were processed for either histology (H&E, toluidine blue) or immunohistochemistry (tryptase, laminin, collagen type IV and VIII, and alpha-SMA) or grown as explants for obtention of fibroblasts. The effects of mast cell (HMC-1) sonicate and selected mast cell mediators and cytokines on fibroblast proliferation ([ (3)H]thymidine) and collagen synthesis ([ (3)H]proline) and on fibroblast contractile activity (tridimensional collagen lattice) were evaluated. Mast cell mediators influencing fibroblast proliferation were partially characterized by enzymatic susceptibility and FPLC gel filtration column chromatography. RESULTS: Most of the fibroblasts in peritoneal adhesions were identified as alpha-SMA-positive myofibroblasts. Mast cell hyperplasia was observed and more than one third of the mast cells were degranulated. Few mast cells showed a faint staining for laminin or collagen type IV and VIII. Mast cell sonicate increased fibroblast proliferation and contractile activity while decreasing collagen synthesis. Mast cell sonicate proliferating activities were found to be proteinase-sensitive with a molecular weight of more than 158 kd, of approximately 40 kd, and of less than 10 kd. TGF-beta and tryptase enhanced collagen synthesis; TNF-alpha and chymase decreased it. None of the selected mediators increased fibroblast proliferation. CONCLUSIONS: Myofibroblasts are the main connective tissue cells present in human peritoneal adhesions, and mast cells play a direct role in peritoneal adhesion formation.     

Combined Application of Acellular Bovine Pericardium and Hyaluronic Acid in Prevention of Postoperative Pericardial Adhesion

An experiment was designed to find the suitable acellular bovine pericardium (ABP) patch in pericardial cavity reconstruction and to evaluate the effect of sodium hyaluronic acid (NaHA) on inflammatory reaction in prevention of pericardial adhesions. The pericardial adhesion model was established in 20 rabbits, weighing from 3.2 to 3.6 kg. Groups were classified as follows: Group A (n = 5), the control group, the pericardium was directly closed; Group B (n = 5), 0.15% glutaraldehyde‐treated ABP (low cross‐link degree); Group C, 0.3% glutaraldehyde‐treated ABP (middle cross‐link degree); Group D, 0.15% glutaraldehyde‐treated ABP + NaHA solution. Blood samples were collected at 6 h, 24 h, 3 days, and 5 days, to assay postoperative inflammatory reaction. The tenacity and severity of adhesions were evaluated 2 months after operation, by macroscopic and microscopic examinations, and Q‐PCR (real‐time quantitative polymerase chain reaction) test was used to quantitatively analyze the associated genes with adhesion. Pericardium regeneration was demonstrated by immunohistochemical technique to identify mesothelial cells. In Group D, the serum concentration of tumor necrosis factor‐α (TNF‐α) was significantly lower in the early postoperative period, and the mean adhesion score (adhesion between the epicardium and ABP) was significantly lower compared with the control group (Groups D vs. A: 0.20 ± 0.45 vs. 2.00 ± 0.71, P = 0.009*). The signs of degradation of the ABPs were observed 2 months postoperation in Groups D and B. Immunohistochemically, the positive cytokeratin AE1 staining results demonstrated the relatively total regeneration of the pericardium in Group D. Signs of regeneration were observed in Group D. Compared with the control group, the level of TGF‐β2 in Group D was significantly lower (0.00132 ± 0.00114, P = 0.022*). The TGF‐β3 level was statistically significant, being highest in Group D (0.00805 ± 0.00136, P = 0.029*). The mean quantity of Smad6 in Group D was also lower than the other groups. Low cross‐link degree ABP may be an efficient physical block between the epicardium and the sternum and also an ideal scaffold for pericardial tissue regeneration, whereas combined use with NaHA may significantly reduce postoperative pericardial adhesions. The signal transduction pathway of transforming growth factor‐β (TGF‐β) and Smad6 may play a key role in the formation of pericardial adhesion.     

The use of an artificial pericardium with a total artificial heart

Postoperative adhesions following open heart surgery enhance the risks and increase the time of subsequent reoperation. When possible, primary closure of the natural pericardium is recommended, particularly in those cases that are more likely to be reoperated upon. The use of a total artificial heart (TAH) as a bridge to transplantation makes reoperation mandatory. If the pleura is left open to accommodate the ventricles, the risk of adhesion is considerable. To address this question, gluteraldehyde-fixed pericardial allografts were evaluated in calves undergoing TAH replacement. Eight animals were implanted with 3 different types of TAHs and survived from 12 to 108 days (mean 52.8 +/- 14.5). The pericardial substitute was wrapped around the TAH and the vascular grafts and cuffs. Two different surgical techniques were evaluated. At the time of autopsy, the presence of adhesions and gross epicardial reaction was macroscopically characterized and classified according to a standardized scale. Bacterial cultures were taken and tissue submitted for histology. The animals implanted with pericardial allografts for periods greater than 3 weeks were observed to have greater adhesions than those implanted for periods less than 3 weeks (p = 0.006). Pericardial cultures were negative in all cases and neovascularization and fibroplasia of the underlying tissues occurred in all cases. Leukocyte infiltration was minimal in the shorter term implant animals. Degeneration of a portion of the pericardium occurred in only 2 cases after 90 days. Minor calcification of the artificial pericardium was noted, but only in the longer term implant animals. The artificial pericardium reduced adhesion, thus facilitating reoperation in implants lasting up to a month.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of chymase inhibition on the arteriovenous fistula stenosis in dogs

It was hypothesized that chymase may participate in hemodialysis vascular access dysfunction, as chymase has been known to be an effective enzyme in the conversion of angiotensin I (Ang I) to Ang II and in the latent TGF-beta1 to the active form. An arteriovenous (AV) fistula was created between the brachial artery and vein in dogs. In the AV anastomosis, when the walls of the venous and arterial sides were compared, the eccentric neointimal formation was most evident in the venous wall. Compared with the venous side downstream of the AV anastomosis, a severe neointimal hyperplasia was found in the venous side upstream of the AV anastomosis (intima/media, 153 +/- 25%). The chymase- and TGF-beta-positive mast cells were markedly accumulated in the proliferous neointima and media. In association with the reduction of chymase expression, a marked decrease in Ang II-, AT(1) receptor-, and TGF-beta-positive areas was achieved by NK3201 (a chymase inhibitor) treatment, and the neointima formation (intima/media: region A, 53 +/- 9%, P < 0.001; region B, 54 +/- 14%, P < 0.001) was also significantly suppressed in this group. Although lisinopril treatment also provided some beneficial effects with regard to the prevention of neointimal formation, the degree was less than that seen with chymase inhibition. These findings indicate that mast cell-derived chymase plays an essential role in the pathogenesis of the AV fistula access failure and that chymase inhibition may be a therapeutic target for the treatment of hemodialysis vascular access dysfunction in clinic settings.     

Immediate hemodynamic effects of pericardial closure after open-heart surgery

Acute hemodynamic effects of a routine pericardial closure after cardiopulmonary bypass was studied in 29 patients undergoing cardiac surgery. Clinically, the pericardial closure was well tolerated. Pericardial closure resulted in an 8% decrease of cardiac output (p less than 0.01) while cardiac index remained normal (2.9 l/min/m2 +/- 0.6 SD). The effect of the pericardium on pulmonary arterial and wedge pressures, and on systemic arterial pressure was not significant. Central venous pressure increased from 8 +/- 2 mmHg to 9 +/- 3 mmHg (p less than 0.05) after pericardial closure and decreased to 7 +/- 3 mmHg (p less than 0.05) when the pericardium was reopened. Left ventricular end-diastolic cavity diameter by echocardiography decreased in 19 of the patients studied from 46 +/- 6 mm to 41 +/- 5 mm (p less than 0.01) when the pericardium was closed, and increased to 45 +/- 6 mm (p less than 0.01) after re-opening of the pericardiotomy incision. The hemodynamic effects of pericardial closure seem to result from limited ventricular filling.     

Can angiotensin converting enzyme inhibitors prevent postoperative adhesions?

BACKGROUND: Peritoneal adhesions are pathological fibrotic bands developing after mesothelial damage. Transforming growth factor beta-1 (TGF-beta1) has mitogenic activities for macrophages and fibroblasts. Over-expression of TGF-beta1 has been implicated in the pathogenesis of several fibrotic disorders. Angiotensin II increases the expression of the TGF-beta1 in fibroblasts. The aim of the study was to investigate the effect of angiotensin converting enzyme inhibitor (ACE) on intraperitoneal adhesions. MATERIALS AND METHODS: Thirty male Wistar albino rats were divided into two groups. In the first procedure, laparotomy was performed through a 3-cm midline incision. Ileum was divided above 10 cm from ileocecal valve and a single-layer ileoileal anastomosis was performed. Although no treatment was given to rats in group 1, lisinopril (an ACE inhibitor) was given to rats in group 2 for postoperative 7 days in drinking water. Estimated amount of supplied lisinopril was 6.5 mg/kg/day. On postoperative 8th day, relaparotomy was performed and adhesions were evaluated. At the same time, blood samples were taken for TGF-beta1 measurements. RESULTS: Adhesion severity was significantly less in the ACE inhibitor group (P < 0.001). While mean TGF-beta1 level was 860.3 +/- 108.1 pg/dl (mean +/- SD) in control group, it was 335.8 +/- 52.4 pg/dl in ACE inhibitor group (P < 0.001). There was a significant correlation between serum TGF-beta1 levels and grade of adhesions (r = 0.948). CONCLUSION: It was concluded that ACE inhibitors might be useful for preventing peritoneal adhesions.     

Evaluation of a bioabsorable polylactide film in a large animal model for the reduction of retrosternal adhesions

Objectives

An adult pig model of retrosternal adhesion formation via an inferior hemisternotomy was used to evaluate the formation and development of pericardial and retrosternal adhesions, as well as adhesion reduction using two thicknesses of a bioabsorbable polylactide film.

Materials and methods

Twenty-five adult female pigs (70 kg) were allocated to either a control group or four different treatments using two thicknesses (0.02 or 0.05 mm) of a polylactide film. In each animal, the film was placed either inside the pericardium or inside and outside the pericardium.

Results

All animals demonstrated adhesions between the posterior and lateral surfaces of the heart and pericardium. Thick fibrous retrosternal adhesions and pericardial adhesions were noted in the control animals with complete obliteration of the anatomical plane. The polylactide films preserved the anatomical planes and reduced the adhesion response.

Conclusions

A reproducible animal model was used to examine the formation and reduction of retrosternal and pericardial adhesions. A polylactide film placed inside the pericardium or between the heart and sternum was able to limit adhesion formation and maintain the anatomical planes, which would facilitate reentry.     

Angiotensin converting enzyme-independent angiotensin ii production by chymase is up-regulated in the ischemic kidney in renovascular hypertension

BACKGROUND: Tissue angiotensin II (ANG II) levels are elevated in both kidneys in renovascular hypertension (RVH). It has been demonstrated previously that intrarenal ANG II is augmented by an angiotensin converting enzyme (ACE) dependent mechanism in the non-ischemic kidney, but the role of ACE-independent production of ANG II in the kidney by the enzyme chymase is unknown. This study tested the hypothesis that intrarenal chymase activity is up-regulated in RVH. METHODS: A two-kidney, one-clip (2K1C) rat model was used to induce RVH (n = 6 rats/group). Regulation of intrarenal chymase activity by plasma ANG II was investigated using an ANG II-infusion model. At sacrifice 14 days post-operatively, steady-state ANG II levels in plasma and kidney were quantified by radioimmunoassay. ANG II production was quantified in kidney homogenates by incubating at 37 degrees C for 60 min with enzyme substrate (200 microm ANG I) alone or substrate containing the chymase inhibitor chymostatin. ANG II was separated and quantitated by HPLC. Chymase activity was defined as the fraction of ANG II production inhibited by Chymostatin. RESULTS: 2K1C and ANG II-infused rats developed significant hypertension, compared to control rats (P = 0.0001 and P = 0.001, respectively). Chymase-dependent ANG II production was increased in the ischemic kidney, but not the non-ischemic kidney, of 2K1C rats compared to control animals (*P < 0.05). Intrarenal chymase activity was unchanged by ANG II infusion (P = NS). CONCLUSIONS: Chymase activity is up-regulated in the ischemic kidney of 2K1C rats. Plasma ANG II does not appear to regulate intrarenal chymase activity, suggesting that ischemia per se up-regulates chymase activity in the kidney. ACE-independent ANG II production by chymase may provide a mechanism for augmenting intrarenal ANG II in the ischemic kidney in RVH.     

Regeneration of pericardial tissue on absorbable polymer patches implanted into the pericardial sac. An immunohistochemical, ultrastructural and biochemical study in the sheep.

A new absorbable polymer prepared from polyhydroxybutyrate (PHB) was inserted as a pericardial patch in sheep to serve as a temporary scaffold for regeneration of pericardial tissue. Postoperative adhesions were rare or absent. The present study focuses on characterization of the regenerated surface cells. The luminal surface of the regenerated tissue was covered with a complete layer of mesothelium-like cells which at light and scanning electron microscopy resembled those in native pericardium. Immunohistochemical stainings for cytokeratin and thrombomodulin were positive in these cells. Heparan sulfate proteoglycan was found in a basement-membrane-like structure beneath the surface cells, as in the normal pericardium. Transmission electron microscopy of the regenerated surface revealed cells with the characteristics of mesothelium. Prostacyclin production in the regenerated tissue was similar to that in native pericardium. The results indicate regeneration of a mesothelial layer with many of the important functions of native mesothelial cells. This may explain the presently and previously observed prevention of pericardial adhesions after cardiac surgery in this field. Clinical testing of PHB patches as pericardial substitutes is warranted in cardiac surgery when pericardial closure is desired.     

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.     

Effect of Chymase-Dependent Transforming Growth Factor β on Peritoneal Adhesion Formation in a Rat Model

Purpose To clarify the role of chymase produced from mast cells, which are closely related to adhesion formation, we investigated the preventive effect of a chymase inhibitor on adhesion formation in a rat model.Methods A lesion was created in rats by uterus scraping, and a chymase inhibitor, Suc-Val-Pro-Phe^p(OPh)₂ (10µM), or a placebo was injected into the abdomen. The level of transforming growth factor (TGF-) in the peritoneal fluid was also measured.Results By 2 weeks after the operation, the scores for adhesion formation in the chymase inhibitor-treated group were significantly lower than those in the placebo-treated group, at 1.64 ± 0.34 and 3.27 ± 0.19, respectively (P < 0.01). After scraping the uterus, the level of TGF- in the peritoneal fluid was significantly higher in the placebo-treated group, whereas it was significantly suppressed by the chymase inhibitor.Conclusions Chymase may play an important role in adhesion formation aided by TGF-.     

Prevention of postoperative pericardial adhesions by closure of the pericardium with absorbable polymer patches. An experimental study.

Pericardial adhesions after cardiac operations are a widely known phenomenon. They may severely complicate reoperations, making reentry hazardous, increasing bleeding, and prolonging the operation time. The anatomic orientation and visibility of both bypass grafts and coronary arteries are also impaired. With the aim of minimizing pericardial adhesions after cardiac operations, we studied the course of tissue regeneration after implantation of a new absorbable patch made from poly-hydroxy-butyrate. A total of 23 sheep were studied. Of these, 18 formed the test group and five served as control animals. The animals were killed at intervals of 2 to 30 months after the operation. In 14 of the 18 test animals no adhesions developed. In three animals loose adhesions were found, and in one with signs of postoperative infection there were moderate, generalized adhesions. All control sheep showed moderate adhesions; no infection was noted in this group. Light microscopy in the test group revealed a layer of mesothelium-like cells facing the epicardial side; this was already present in the early specimens. Poly-hydroxy-butyrate appeared to be slowly phagocytosed by polynucleated macrophages, which were still found occasionally in the late samples. Lymphocytes and platelets were rare. Scanning electron microscopy showed, on the epicardial side of the regenerated tissue, a mesothelium-like lining that completely covered the underlying collagen layer. The surface cell morphology grossly resembled that of native pericardium. It was concluded that in this animal model poly-hydroxy-butyrate pericardial patches decreased adhesions and preserved coronary anatomy. The findings in the control group demonstrated that pericardial surgery in the sheep was associated with adhesion formation.