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PubMed1990

Interaction of plasminogen and fibrin in plasminogen activation.

Glu1-, Lys77-, miniplasminogens, kringle 1-3, kringle 1-5A, and kringle 1-5R were able to bind with fibrin, while microplasminogen and kringle 4 did not bind significantly. Kringle 1-5A, but not kringle 1-3, effectively inhibited the binding of Glu1-, Lys77-, and miniplasminogens with fibrin. Miniplasminogen also inhibited the binding of Glu1-plasminogen with fibrin. The binding of kringle 1-3 with fibrin was blocked by mini- or Glu1-plasminogen. It is therefore evident that there are two fibrin-binding domains in plasminogen and that the one in kringle 5 is of higher affinity than that in kringle 1-3. CNBr cleavage products of fibrinogen effectively enhanced the activation of Glu1-, Lys77-, or miniplasminogens, but not microplasminogen, by tissue-type plasminogen activator. Kringle 1-5, but not kringle 1-3, dose-dependently inhibited the enhancement by fibrinogen degradation products of Glu1-plasminogen activation by the activator. Lysine and epsilon-aminocaproic acid could inhibit the binding of plasminogens and plasminogen derivatives with fibrin and block the enhancement effect of fibrinogen degradation products on plasminogen activation. The data clearly illustrate that the binding of plasminogen with fibrin, mainly determined by kringle 5, is essential for effective activation by tissue-type plasminogen activator. However, the presence of kringle 1-4 in the plasminogen molecule is required for the full enhancing effect since the kcat/Km of miniplasminogen activation in the presence of fibrinogen degradation products was 8.2 microM-1 min-1 which is significantly less than 52.0 microM-1 min-1 of Glu1-plasminogen.

Aminocaproic Acid↗
PubMed1987

Zinc alters fibrin ultrastructure.

Turbidimetric studies indicate that Zn(II) accelerates fibrin gelation [decreases clotting time (CT)] and increases maximal fibrin clot turbidity. For any given level of fibrinogen (0.2-2.6 mg/ml), the relative fibrin turbidity of thrombin-induced clots increases with Zn(II) in a concentration dependent manner. Zinc-associated turbidity increases are also observed in the presence of 2 mM (Ca(II). With citrate, similar turbidity increases are observed, though at higher cation levels. Thus, turbidimetry indicates that the gel formed with Zn(II) is coarser, or has thicker fibre strands. SEM micrographs confirm that fibre thickness ranges from 260 A to 2600 A, when Zn(II) levels range from 0-50 uM. With citrate, TEM micrographs reveal a more than 20 X fold increase in fibre diameter (100 A- greater than 2000 A) with higher Zn(II) (less than 1 mM) levels. Based on a fibrin monomer cross-section of approximately 60 A, the electron micrographs indicate that depending on the Zn(II) levels, fibrin strands are composed of between 2 to 40 monomeric fibrin molecules. Thus, at physiologically relevant levels, Zn(II) can drastically modulate fibrin ultrastructure.

Fibrin↗
PubMed1996

Conjunctive administration of intravenous heparin attenuates cross-linked fibrin degradation in patients treated with streptokinase.

Increases in thrombin activity occur in patients treated with streptokinase, but conjunctive therapy with intravenous heparin does not appear to improve either the rate of early infarct artery patency or survival in patients with acute myocardial infarction. In a recent study we found that concentrations of fibrinopeptide A, a marker of thrombin-mediated fibrin formation, were lower in the first 3 h in patients treated with intravenous heparin (5000 U bolus followed by a fixed-dose 1000 U/h infusion, n = 14) compared with subcutaneous (12,500 U every 12 h, started 4 h after streptokinse, n = 14) administration, but were increased in both groups of patients, consistent with persistent thrombin activity. To determine whether the differential effects of the intensity of heparinization on thrombin formation were reflected in differences in fibrin degradation, we measured cross-linked fibrin degradation products (XL-FDP) before and 1, 2, 3, 8, 12, and 24 h after streptokinase in the same cohort of patients, with a new ELISA with a D-dimer-specific capture antibody (MAb 3B6) and a fibrin-specific tag antibody (MAb 1D2, Agen, Brisbane, Australia). The incidence of early coronary recanalization assessed by creatine-kinase MM isoforms (increase in activity > or = 0.18%/min), was similar in both groups (79 vs 86%). Concentrations of XL-FDP were similar in patients with and without recanalization, but were lower in patients treated with intravenous compared with subcutaneous heparin at 8 h, but the results did not reach statistical significance (627 +/- 151 ng/ml versus 1007 +/- 157 ng/ ml, p = 0.06), and were significantly lower at 12 h (327 +/- 72 versus 781 +/- 162 ng/ml, p = 0.03 at 12 h) (mean +/- SEM). Concentrations of cross-linked fibrin degradation products were also lower in patients in whom the activated partial thromboplastin time was greater than two times the control, compared with those with inadequate anticoagulation (498 +/- 105 versus 1084 +/- 179 ng/ml; p = 0.02) (mean +/- SEM). Thus, more effective inhibition of thrombin with conjunctive intravenous heparin therapy results in less cross-linked fibrin turnover in the first 12 h after thrombolysis with streptokinase. This probably reflects decreased fibrin formation with therapeutic anticoagulation.

Cohort Studies↗
PubMedDate not supplied

Closure of mucosal defects over exposed mandibular plates using fibrin glue.

BACKGROUND: Mandibular plates may become exposed following radiation therapy, infection, and mucosal necrosis. This may lead to early removal of the mandibular plates with subsequent instability of bone fragments. OBJECTIVE: To compare fibrin glue, a bioadhesive, with traditional sutures in closing mucosa over exposed mandibular plates in a cat. DESIGN: Prospective matched-pairs analysis. SUBJECTS: Nine cats were used, and each cat served as its own control. INTERVENTION: Bilateral mandibular plates were fixed on the buccal side of the mandible of 9 cats. The surgical defects over the plates were left uncovered. After 4 days, the plates on the right side were covered with a mucosal graft fastened with fibrin glue, and on the left side the grafts were secured with sutures. After 10 days, the grafts were excised and a histological examination was performed. RESULTS: The mean operative time for coverage was 2 minutes 11 seconds for the fibrin glue and 12 minutes 48 seconds for the sutures (P < .001). Gross examination revealed granulation or ulceration in 3 of the fibrin and 9 of the suture specimens (P < .005). All specimens displayed mild-to-moderate acute and chronic inflammation. All sutured specimens showed focal foreign body-type giant cells surrounding fragments of bone and suture. Two mandibular plates were partially exposed on the fibrin glue side. CONCLUSIONS: The use of fibrin glue to cover exposed mandibular plates is safe and well tolerated in cats. Glue application requires a shorter operative time and is associated with fewer occurrences of granulation and ulceration when compared with suture fixation. Further studies are indicated to titrate the concentration of fibrin glue and to prevent plate exposure.

Animals↗
PubMed2000

Argatroban inhibits intraocular fibrin formation after vitrectomy in rabbits.

OBJECTIVES: To examine whether the specific thrombin inhibitor argatroban can prevent anterior chamber, pupillary area, and anterior vitreous fibrin formation after vitrectomy and lensectomy in rabbits. METHODS: Argatroban was infused into the vitreous cavities of Japanese albino rabbits for 5 minutes after pars plana vitrectomy and lensectomy. Slitlamp microscopy and indirect ophthalmoscopy were performed at postoperative hours 0.5, 1, 2, 3, and 6, and at postoperative days 1, 2, 3, and 7, and the amounts of fibrin formation in the anterior chamber, pupillary area, and anterior vitreous were scored from grade 0 to 4. RESULTS: Argatroban prevented fibrin formation from 0.5 hours postoperatively in a dose-dependent manner. In the eyes treated with 0.01% argatroban, the median score for postoperative fibrin formation was significantly less than that in control eyes between hours 1 and 3 (hour 1, P =.02; hour 2, P =.005; and hour 3, P =.003); the eyes treated with 0.003% argatroban also had significantly less fibrin than control eyes between 1 and 2 hours (hour 1, P =.005; hour 2, P =.03). CONCLUSION: These results indicate that argatroban inhibits intraocular fibrin formation in an experimental rabbit model. CLINICAL RELEVANCE: Argatroban may be useful clinically in cases that often produce fibrin postoperatively, such as proliferative vitreoretinopathy and proliferative diabetic retinopathy.

Animals↗
PubMed1988

Fibrin sealant in high-risk colonic anastomoses.

The use of fibrin sealant has been advocated to enhance the healing of high-risk intestinal anastomoses. Colonic anastomoses were performed in 162 rats randomly assigned to four groups: control animals with or without fibrin sealant applied to the anastomosis and steroid-treated animals with or without fibrin sealant. At five days postoperatively, the use of steroids alone significantly reduced the anastomotic bursting pressure (ABP) and enhanced abscess and adhesion formation. The addition of fibrin sealant to the anastomosis in steroid-treated animals did not improve ABP and, in fact, further increased abscess formation. In control animals, the use of fibrin sealant also reduced ABP and enhanced abscess and adhesion formation. By ten days, there was no difference in ABP among the groups, and the rate of abscess formation was reduced in all groups. These findings indicated that short-term treatment with steroids delayed colonic anastomotic healing. Fibrin sealant did not enhance the integrity of these high-risk anastomoses. The present data do not support the use of fibrin sealant in high-risk colonic anastomoses.

Abscess↗
PubMed1992

Decreased wound contraction with fibrin glue--treated skin grafts.

Skin grafts can be used effectively to inhibit wound contraction. A critical element of this inhibition is the adherence of the graft to the wound bed. Fibrin glue has been shown to increase the adherence of skin grafts to wound beds. We therefore devised an experiment to determine the effect of fibrin glue on skin graft inhibition of wound contraction. Two 2.5 x 2.5-cm full-thickness defects were created on the dorsa of 15 Sprague-Dawley rats. Thirty partial-thickness grafts were harvested from isogeneric donor animals using a brown dermatome. Prior to grafting, one full-thickness defect, each animal received 0.2 mL of fibrin glue (Immuno AG, Vienna, Austria). The adjacent wound served as the control and received 0.2 mL of normal saline. Grafts were applied, sutured, and protected with an occlusive dressing. The size of graft sites treated with fibrin glue or normal saline was determined at the time of graft application and thereafter at 3-day intervals for 21 days using standardized photographic techniques. The percentage of change from initial wound size at each point was recorded for each group. Graft sites treated with fibrin glue contracted less than the controls from the ninth postgraft day to the completion of the study. The mechanism by which fibrin glue inhibits wound contraction may be related to increased adherence of grafts to the underlying wound bed. As an adjunct in skin grafting, fibrin glue may offer certain advantages that are not achieved by suturing alone.

Animals↗
PubMed1995

Fibrin glue sealing for the prevention of pancreatic fistulas following distal pancreatectomy.

OBJECTIVE: To evaluate the use of fibrin glue sealing of the pancreatic stump for the prevention of postoperative pancreatic fistulas. DESIGN: A prospective, randomized clinical trial. PATIENTS AND METHODS: Fibrin glue is a biologic adhesive consisting of highly concentrated human fibrinogen, thrombin, and factor VIII. Twenty-six of 56 patients who underwent distal pancreatectomy for gastric cancer or pancreatic disease were randomly assigned to the fibrin glue group. Fibrin glue was applied to the suture line of the pancreatic stump with the ligated main pancreatic duct. Pancreatic fistula was defined as a pancreatic fluid discharge for over 7 post-operative days diagnosed by local findings, with amylase concentration in the discharge fluid more than three times the serum amylase concentration, a level low enough that even a small pancreatic leakage could be diagnosed. RESULTS: The overall incidence of pancreatic fistula was 28.6%. Postoperative pancreatic fistulas occurred in four patients (15.4%) in the fibrin glue group and 12 (40.0%) in the control group (P = .04). The lower pancreatic fistula rate was seen in the fibrin glue group also when analyzing patients with gastric cancer or pancreatic disease only, although there was no statistically significant difference. CONCLUSIONS: Intraoperative use of fibrin glue following distal pancreatectomy could prevent pancreatic fistula formation. This method was feasible, safe, and reliable and will complement other prophylactic methods.

Adult↗
PubMed1998

Addition of fibrin sealant to ceramic promotes bone repair: long-term study in rabbit femoral defect model.

Despite their impact on the healing of soft connective tissue, fibrin sealants have not been shown conclusively to have an important role in the healing of bone defects. We report the positive influence of fibrin sealants on repair of cancellous bone cavities filled with a porous, resorbable ceramic. We studied two fibrin sealants: Autocolle and Tissucol. Autocolle is enriched in platelet factors during its preparation. Tissucol is a commercially available fibrin glue prepared from pooled human plasma that has no enrichment in platelet factors. Cavities 10 mm in depth and 5 mm in diameter were drilled in lateral condyles of 45 New Zealand rabbits. These defects were filled with either coral granules or a mixture of fibrin sealant (Autocolle or Tissucol) and coral granules or left empty. At 1 month addition of a fibrin sealant (Autocolle or Tissucol) to the coral led to a significant increase in bone formation in comparison to coral alone. At 2 months significant fibrin sealant mediated enhancement of bone repair was observed with Autocolle only. At 6 months bone formation was similar to the adult bone amount in nonoperated animals, whatever the initial material. Control cavities, on the other hand, were invaded with fibrous tissue only at each time period.

Animals↗
PubMed1999

Attachment of periosteal grafts to articular cartilage with fibrin sealant.

Favorable results using fibrin sealants in vascular surgery and soft tissue reconstruction have prompted investigation of these biologic adhesives for orthopedic applications. One important recent application was as a sealant for periosteal grafts applied to defects in articular surfaces, a procedure that contained injected chondrocytes cultured in vitro. The low and variable adhesive strength of autologous fibrin substances prompted our investigation of allogeneic fibrin. An in vitro test method was developed to investigate the use of a fibrin sealant for attaching periosteal (bovine) patches to articular cartilage (bovine). Dermis-dermis (porcine) adhesion also was evaluated. In tests of the periosteum-to-cartilage bond performed in a physiological environment, we determined the effects of the following variables on the adhesive shear strength: set time, source of fibrinogen (bovine versus human), and fibrinogen concentration. A specially designed test rig was developed to avoid nonshear force components. Adhesive shear strength increased with fibrin set time for both fibrinogen concentrations and sources (p <.03). The 30-min set time yielded data with less variance than the 5-min set time in all cases except with the higher human fibrinogen concentration (50-80 mg/mL). While there was a trend at each set time towards greater shear strength with increased protein concentration (50-80 mg/mL versus 25-40 mg/mL), only the 5-min trial of the bovine product provided a significant advantage (p <.006). There was no significant difference in adhesive strength between the fibrin products produced with human and bovine fibrinogen. The periosteum-cartilage adhesive strengths obtained in our model were comparable to values recorded for the dermis-dermis bonding. The greater strength at the 30-min set time suggests that a certain time period of joint immobilization might be beneficial in procedures in which grafts are glued to articular cartilage. This study has shown that adhesive strengths achieved with fibrin glues in treating skin wounds also can be achieved in the attachment of periosteal grafts to articular cartilage.

Animals↗
PubMed2006

Kinetics of the interaction of desAABB-fibrin monomer with immobilized fibrinogen.

The soluble and stable fibrin monomer-fibrinogen complex (SF) is well known to be present in the circulating blood of healthy individuals and of patients with thrombotic diseases. However, its physiological role is not yet fully understood. To deepen our knowledge about this complex, a method for the quantitative analysis of interaction between soluble fibrin monomers and surface-immobilized fibrinogen has been established by means of resonant mirror (IAsys) and surface plasmon resonance (BIAcore) biosensors. The protocols have been optimized and validated by choosing appropriate immobilization procedures with regeneration steps and suitable fibrin concentrations. The highly specific binding of fibrin monomers to immobilized fibrin(ogen), or vice versa, was characterized by an affinity constant of approximately 10(-8)M, which accords better with the direct dissociation of fibrin triads (KD approximately 10(-8) -10(-9) M) (J. R. Shainoff and B. N. Dardik, Annals of the New York Academy of Science, 1983, Vol. 27, pp. 254-268) than with earlier estimations of the KD for the fibrin-fibrinogen complex (KD approximately 10(-6) M) (J. L. Usero, C. Izquierdo, F. J. Burguillo, M. G. Roig, A. del Arco, and M. A. Herraez, International Journal of Biochemistry, 1981, Vol. 13, pp. 1191-1196).

Biopolymers↗
PubMed2005

Bone repair with a form of BMP-2 engineered for incorporation into fibrin cell ingrowth matrices.

Most growth factors naturally involved in development and regeneration demonstrate strong binding to the extracellular matrix and are retained there until being locally mobilized by cells. In spite of this feedback between cell activity and growth factor mobilization in the extracellular matrix, this approach has not been extensively explored in therapeutic situations. We present an engineered bone morphogenetic protein-2 (BMP-2) fusion protein that mimics such function in a surgically relevant matrix, fibrin, incorporated into the matrix until it is locally liberated by cell surface-associated proteases. A tripartite fusion protein, denoted TG-pl-BMP-2, was designed and produced recombinantly. An N-terminal transglutaminase substrate (TG) domain provides covalent attachment to fibrin during coagulation under the influence of the blood transglutaminase factor XIIIa. A central plasmin substrate (pl) domain provides a cleavage site for local release of the attached growth factor from the fibrin matrix under the influence of cell-activated plasmin. A C-terminal human BMP-2 domain provides osteogenic activity. TG-pl-BMP-2 in fibrin was evaluated in vivo in critical-size craniotomy defects in rats, where it induced 76% more defect healing with bone at 3 weeks with a dose of 1 mug/defect than wildtype BMP-2 in fibrin. After a dosing study in rabbits, the engineered growth factor in fibrin was evaluated in a prospective clinical study for pancarpal fusion in dogs, where it induced statistically faster and more extensive bone bridging than equivalent treatment with cancellous bone autograft. The strong healing response shown by fibrin including a bound BMP-2 variant suggests that with the combination of bound growth factor and ingrowth matrix, it may be possible to improve upon the natural growth factor and even upon tissue autograft.

Animals↗
PubMed2007

Fibrin gel improved the spatial uniformity and phenotype of human chondrocytes seeded on collagen scaffolds.

A scaffold made of equine collagen type I based material has been assessed for its use in the preparation of tissue-engineered cartilage implants with human articular chondrocytes. Improvements of cell-seeding efficiency and specific gene expression were studied by combining solid scaffold with fibrin glue or human blood plasma. Following 3 weeks of static culture, mRNA expression levels of collagen type I, collagen type II, aggrecan and versican were analyzed by real-time quantitative PCR and compared to those in native cartilage and monolayer cell cultures. Constructs prepared with fibrin glue or plasma showed higher cell seeding efficiencies than those prepared without gel. Chondrocytes seeded directly onto a collagen scaffold appeared fibroblastic in shape while those encapsulated in fibrin gel were spherical. The presence of fibrin glue positively influences on mRNA levels of collagen type II and aggrecan, while blood plasma enhanced only the level of collagen type II expression. Levels of collagen type I and versican decreased in presence of fibrin glue. In orthopaedics, the combination of solid collagen fleece with fibrin gel for implant preparation is seen to be preferred over solid material or even cells in a suspension, since fibrin gel improves seeding capacity of the scaffold, supports equal distribution of cells and stimulates higher chondrogenic phenotype expression.

Adult↗
PubMed1988

Apatite-wollastonite containing glass ceramic-fibrin mixture as a bone defect filler.

The purpose of this study was to evaluate the usefulness of a mixture of apatite-wollastonite containing glass ceramic (A-W.GC, 42-60 mesh in granule size) with fibrin as a bone defect filler. A bone defect was drilled in the proximal metaphysis of the rat tibia and was filled with (1) fibrin glue, (2) A-W.GC granules, or (3) A-W.GC-fibrin mixture. Nothing was placed in the defect of the controls. The animals were serially sacrificed until 8 weeks after the operation, and the defect site was histologically examined and histomorphometrically analyzed for quantitative evaluation of newly formed bone and blood vessels. The use of fibrin glue as the binder markedly increased the ease of handling the A-W.GC granules. In the controls, little trabecular regeneration was observed in the defect site. Early vascularization (confirmed by microangiography) increased and the repairing process was accelerated in the defects filled with fibrin. In these defects filled with A-W.GC granules, good bone formation was observed around the granules. Bone formation was accelerated in the defects filled with A-W.GC fibrin mixture. Thus, the mixture showed good osteoconductive potential as well as acceleration of the repair process. Therefore, A-W.GC-fibrin mixture is considered to be a useful bone defect filler.

Animals↗
PubMed1989

Cultures of fibroblasts in fibrin lattices: models for the study of metabolic activities of the cells in physiological conditions.

Two techniques for fibroblast culture in three-dimensional fibrin matrices (fibrin lattices) were used to study the behavior and metabolism of cells in this physiological support. When the fibrin lattices were prepared in silicone-coated glass petri dishes, fibroblasts induced retraction of lattices to an extent dependent on both cell density and serum concentration, the cells stopped dividing, and their protein and collagen syntheses proceeded at a lower rate, like that in collagen lattices. When fibrin lattices were prepared in plastic petri dishes, the matrix attached to the walls, there was no retraction, and the protein synthesis was very active even as regards collagen. The optimal concentration of ascorbic acid in nonretracting fibrin lattices was lower (10 micrograms/ml) than in monolayers (50 micrograms/ml). The comparison of collagen and fibrin lattices showed that the collagenic nature of the lattice was not compulsory for supporting the phenomenon of retraction and that fibroblasts, when exposed to a stress in a fibrin matrix prevented from retracting, secreted far more collagen.

Ascorbic Acid↗
PubMed1992

Use of fibrin glue to minimize bleeding of microvascular repairs in hypertensive rats.

The purpose of this study is to describe our technique of applying fibrin glue at the microvascular anastomotic site and to evaluate the effect of fibrin glue on anastomotic hemostasis and patency under various high pressure states using dopamine-induced acute hypertension in rats. A total of 72 male Wistar Kyoto rats, 10 weeks old, were used in this study. Under urethane anesthesia, end-to-end anastomosis of the left femoral artery was performed using 10-0 nylon suture by the standard interrupted suture technique. Pasteurized fibrin glue was then topically applied upon the suture line of the anastomosis. Thirty-six normotensive rats were divided into three groups based on the number of sutures (4, 6, or 8) used to complete the anastomosis. Groups were subdivided, half receiving fibrin glue application and half without. Thirty-six dopamine-induced acutely hypertensive rats were divided into three groups based on the blood pressure levels of 150, 200, and 250 mmHg, respectively. These groups were again subdivided, with half receiving glue applications. Microvascular anastomosis was performed using 6 nylon sutures. Patency rates and anastomotic bleeding were evaluated. The results revealed that successful anastomoses could be performed with fewer sutures when fibrin glue was used as a reinforcement at the anastomosis. Fibrin glue was also effective at the maximum blood pressure (250 mmHg) with no anastomotic leakage and no decrease in postoperative patency rate. These results suggest that conventional microsurgical suturing technique combined with fibrin glue would be effective in the prevention of leakage in microsurgical repairs, even under conditions of high blood pressure.

Anastomosis, Surgical↗
PubMed1994

Fibrinolysis-resistant fibrin deposits in minor labial salivary glands of patients with Sjögren's syndrome.

Minor labial salivary glands obtained at biopsy from 12 patients with Sjögren's syndrome were investigated by immunomorphological methods for the presence of fibrinolysis-resistant fibrin deposition. Fibrin could be found in extracellular localization between individual inflammatory cells infiltrating minor salivary glands. In the areas surrounding mononuclear infiltrations the labeling for fibrin showed an essentially fibrillar pattern. Staining for factor XIII A was observed over fibrin deposits and in large, stellate cells not showing reaction for fibrin. Here it is demonstrated that factor XIII A+ tissue macrophages are in an intimate relationship with fibrin deposits. The authors suggest that tissue macrophages may play a regulatory role in fibrin accumulation in association with autoimmune inflammation and consequently in demarcation of the inflamed tissue.

Adult↗
PubMed1994

How to improve the uterotomy healing. I. Effects of fibrin and tumor necrosis factor-alpha in the rat uterotomy model.

Suboptimal uterotomy healing following cesarean delivery or metroplastic operations may lead to considerable complications. New insights in the biology of wound healing and the availability of a variety of biologic response modifiers open the possibility to modulate the process of wound healing in order to gain clinical benefits. Can uterotomy healing be improved by local application of biosubstances? We developed an uterotomy model in the rat and measured the bursting pressure at defined times postwounding as a functional parameter of wound healing. In addition, the healing process was assessed by serial light microscopic histology. Uterotomy healing was investigated in the presence of fibrin alone or with fibrin containing tumor necrosis factor-alpha (TNF-alpha-fibrin) compared to controls. The fibrin matrix incorporated into rat uterotomies reduced wound hemorrhage and led to a 45% increase of early (Day 3) bursting pressure (not significant). With 20 micrograms TNF-alpha in the fibrin matrix, Day 3 bursting pressure was elevated by more than 100% (P < 0.05). Histologically, inflammation and granulation tissue formation was markedly enhanced. Two micrograms of TNF-alpha/wound did not show any effect and 200 micrograms TNF-alpha even led to a decrease in early bursting strength. After 1 week, no differences in bursting pressure or wound histology could be detected between uterotomies treated with fibrin or TNF-alpha-fibrin compared to controls. The rat uterotomy model appears to be suitable for investigating new biological means to improve uterine wound healing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗