fibrin and Carotid-Artery-Diseases

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies.. Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment.

Topics: Atherosclerosis; Carotid Arteries; Carotid Artery Diseases; Endothelium, Vascular; Fibrin; Forecasting; Humans; Lipids; Macrophages; Magnetic Resonance Angiography; Molecular Imaging; Molecular Probes; Neovascularization, Pathologic; Peptide Hydrolases; Plaque, Atherosclerotic; Vascular Remodeling

Carotid atherosclerosis is a leading cause of cerebrovascular events. The control of cardiovascular risk factors, i.e. tobacco smoking, alcohol abuse, hypertension, dyslipidemia, diabetes and obesity proved to reduce number of fatal and non-fatal strokes but failed to prevent important number of them. Screening for biomarkers in individuals at high risk of symptomatic vascular disease helped to identify some of them. However, as disease is by its nature multifocal, global testing for biomarkers may have limited practical application. New imaging techniques, including direct visualization of artery metabolism, by 18-FDG-PET, has brought new tools to study local atherosclerosis progression and individual plaque metabolic activity. Advances in molecular biology helped to identify inflammatory genes and its strong link to angiogenesis. The later, is thought to play a key role in the transformation to unstable plaque. Studies of the complex role that plays angiogenesis in plaque development will help in future to design effective therapies addressed at the individual cell level. The purpose of the review is to bring new insights into complicated pathophysiology of carotid atherosclerosis.

Topics: Biomarkers; C-Reactive Protein; Carotid Artery Diseases; Endothelium, Vascular; Fibrin; Fibrinogen; Humans; Inflammation; Neovascularization, Pathologic; Stroke; Tunica Intima

Topics: Arteriosclerosis; Carotid Artery Diseases; Coronary Disease; Endothelium, Vascular; Fibrin; Humans; In Vitro Techniques; Lipoprotein(a); Monocyte Chemoattractant Proteins; Risk Factors; Transforming Growth Factor beta

It is known that both platelets and coagulation strongly influence infarct progression after ischemic stroke, but the mechanisms and their interplay are unknown. Our aim was to assess the contribution of the procoagulant platelet surface, and thus platelet-driven thrombin generation, to the progression of thromboinflammation in the ischemic brain.. We present the characterization of a novel platelet and megakaryocyte-specific TMEM16F (anoctamin 6) knockout mouse. Reflecting Scott syndrome, platelets from the knockout mouse had a significant reduction in procoagulant characteristics that altered thrombin and fibrin generation kinetics. In addition, knockout mice showed significant defects in hemostasis and arterial thrombus formation. However, infarct volumes in a model of ischemic stroke were comparable with wild-type mice.. Platelet TMEM16F activity contributes significantly to hemostasis and thrombosis but not cerebral thromboinflammation. These results highlight another key difference between the roles of platelets and coagulation in these processes.

Topics: Animals; Anoctamins; Blood Coagulation; Blood Platelets; Carotid Artery Diseases; Disease Models, Animal; Encephalitis; Fibrin; Hemostasis; Infarction, Middle Cerebral Artery; Kinetics; Megakaryocytes; Mice, Inbred C57BL; Mice, Knockout; Phosphatidylserines; Phospholipid Transfer Proteins; Platelet Activation; Signal Transduction; Thrombin; Thrombosis

Coagulation factor XI is proposed as therapeutic target for anticoagulation. However, it is still unclear whether the antithrombotic properties of factor XI inhibitors influence atherosclerotic disease and atherothrombosis. Our aim is to investigate whether factor XI antisense oligonucleotides could prevent thrombus formation on acutely ruptured atherosclerotic plaques.. Atherosclerotic plaques in the carotid arteries of Apoe(-/-) mice were acutely ruptured using ultrasound. The subsequent thrombus formation was visualized and quantified by intravital microscopy and immunohistochemistry. Mice were pretreated with either factor XI antisense or nonsense oligonucleotides (50 mg/kg) to lower factor XI plasma levels. A tail bleeding assay was used to determine the safety. On plaque rupture, initial platelet adhesion and platelet plug formation were not impaired in animals treated with factor XI antisense oligonucleotides. However, the ensuing thrombus formation and fibrin deposition were significantly lower after 5 to 10 minutes (P<0.05) in factor XI antisense oligonucleotide-treated animals without inducing a bleeding tendency. Furthermore, thrombi from antisense-treated animals were less stable than thrombi from placebo-treated animals. Moreover, macrophage infiltration and collagen deposition were lower in the carotid arteries of factor XI antisense-treated animals. No neutrophils were present.. Factor XI antisense oligonucleotides safely prevent thrombus formation on acutely ruptured atherosclerotic plaques in mice. Furthermore, perturbed carotid arteries from factor XI antisense-treated animals show a less severe inflammatory response.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Blood Coagulation; Blood Platelets; Carotid Arteries; Carotid Artery Diseases; Cholesterol, Dietary; Collagen; Disease Models, Animal; Factor XI; Fibrin; Inflammation; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligonucleotides, Antisense; Plaque, Atherosclerotic; Platelet Adhesiveness; Platelet Aggregation; Rupture, Spontaneous; Thrombosis; Time Factors

Epidemiological, biological and clinical links between periodontal and cardiovascular diseases are now well established. Several human studies have detected bacterial DNA corresponding to periodontal pathogens in cardiovascular samples. Intraplaque hemorrhage has been associated with a higher risk of atherosclerotic plaque rupture, potentially mediated by neutrophil activation. In this study, we hypothesized that plaque composition may be related to periodontal pathogens.. Carotid culprit plaque samples were collected from 157 patients. Macroscopic characterization was performed at the time of collection: presence of blood, lipid core, calcification and fibrosis. Markers of neutrophil activation released by carotid samples were quantified (myeloperoxidase or MPO, cell-free DNA and DNA-MPO complexes). PCR analysis using specific primers for Porphyromonas gingivalis, Aggregatibacter actinomycetemcommitans, Treponema denticola, Prevotella intermedia and Tannerella forsythia was used to detect DNA from periodontal pathogens in carotid tissues. In addition, bacterial lipopolysaccharide (LPS) and Immunoglobulins G against T. forsythia were quantified in atherosclerotic carotid conditioned medium.. Intraplaque hemorrhage was present in 73/157 carotid samples and was associated with neutrophil activation, reflected by the release of MPO, cell-free DNA and MPO-DNA complexes. LPS levels were also linked to intraplaque hemorrhage but not with the neutrophil activation markers. Seventy-three percent of the carotid samples were positive for periodontal bacterial DNA. Furthermore, hemoglobin levels were associated with the detection of T. forsythia and neutrophil activation/inflammation markers.. This study suggests a potential role of periodontal microorganisms, especially T. forsythia, in neutrophil activation within hemorrhagic atherosclerotic carotid plaques.

Topics: Aged; Aged, 80 and over; Antibodies, Bacterial; Bacteroidaceae; Carotid Artery Diseases; Carotid Artery Thrombosis; Dental Plaque; DNA, Bacterial; Endarterectomy, Carotid; Extracellular Traps; Female; Fibrin; Hemorrhage; Humans; Lipids; Male; Middle Aged; Neutrophil Infiltration; Neutrophils; NF-kappa B; Periodontitis; Peroxidase; Plaque, Atherosclerotic; Respiratory Burst

Proteins are major plaque components, and their degradation is related to the plaque instability. We sought to assess the feasibility of magnetization transfer (MT) magnetic resonance (MR) for identifying fibrin and collagen in carotid atherosclerotic plaques ex vivo.. Human carotid artery specimens (n = 34) were obtained after resection from patients undergoing endarterectomy. MR was completed within 12 hr after surgery on an 11.7T MR microscope prior to fixation. Two sets of T1W spoiled gradient echo images were acquired with and without the application of a saturation pulse set to 10 kHz off resonance. The magnetization transfer ratio (MTR) was calculated, and the degree of MT contrast was correlated with histology.. MT with appropriate calibration clearly detected regions with high protein density, which showed a higher MTR (thick fibers (collagen type I) (54 ± 8%)) compared to regions with a low amount of protein including lipid (46 ± 8%) (p = 0.05), thin fibers (collagen type III) (11 ± 6%) (p = 0.03), and calcification (6.8 ± 4%) (p = 0.02). Intraplaque hemorrhage (IPH) with different protein density demonstrated different MT effects. Old (rich in protein debris) and recent IPH (rich in fibrin) had a much higher MTR 69 ± 6% and 55 ± 9%, respectively, compared to fresh IPH (rich in intact red blood cells)(9 ± 3%).. MT MR enhances plaque tissue contrast and identifies the protein-rich regions of carotid artery specimens. The additional information from MTR of IPH may provide important insight into the role of IPH on plaque stability, evolution, and the risk for future ischemic events.

Topics: Aged; Analysis of Variance; Biomarkers; Boston; Carotid Arteries; Carotid Artery Diseases; Collagen; Endarterectomy, Carotid; Feasibility Studies; Female; Fibrin; Fibrosis; Humans; Lipids; Magnetic Resonance Imaging; Male; Middle Aged; Predictive Value of Tests

Atherosclerosis involves all the layers of the artery wall, but the events involving the intimal portion are fundamental to understand the evolution and gravity of lesions. This study shows that scanning microscopy is instrumental for better understanding the physiopathology of this disease.

Topics: Basement Membrane; Carotid Arteries; Carotid Artery Diseases; Disease Progression; Endothelial Cells; Fibrin; Foam Cells; Humans; Microscopy, Electron, Scanning; Plaque, Atherosclerotic; Tunica Intima

Urokinase plasminogen activator (uPA) is strongly expressed in atherosclerotic lesions, but the overall effect of the protease on plaque composition and growth remains controversial. In the present study, apolipoprotein E-deficient (apoE(-/-)) mice were intercrossed with mice which were lacking the uPA gene (doubleknockout; DKO). In ferric chloride-induced carotid artery lesions in chow-fed mice, uPA deficiency increased neointimal size (P = 0.015) and luminal stenosis (P = 0.014), while reducing media thickness (P = 0.002). A lack of uPA also increased the size of and the luminal obstruction from atherosclerotic plaques at the coronary and brachiocephalic arteries of apoE(-/-) mice. Plaques were characterised by a higher fibrinogen/fibrin content and a decrease in cellularity and collagen content. When apoE(-/-) and DKO mice were analysed as a single group, a significant correlation was found between the alpha-actin (smooth muscle cell) and collagen content of atherosclerotic lesions (r = 0.554; P < 0.05), and a negative correlation existed between the alpha-actin and fibrin/fibrinogen immunopositive area (r = -0.791; P < 0.001). Further analysis of brachiocephalic atherosclerosis, a predilection site for plaque rupture in the apoE(-/-) mouse, revealed signs of plaque vulnerability, including a reduced cap-to-intima ratio (0.21 +/- 0.04 vs. 0.37 +/- 0.05; P = 0.03) and more frequent detection of intraplaque haemorrhage (56% vs. 13%; P < 0.01) and buried fibrous caps (1.8 +/- 0.5 vs. 0.5 +/- 0.2; P = 0.02) in DKO compared to apoE(-/-) mice. These results indicate that, at least at (patho)physiologic concentrations, uPA is essential for maintaining the cellularity and collagen content and, possibly, the stability of lesions, both by preventing excessive intramural fibrin accumulation and by facilitating cell migration and invasion.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Carotid Artery Diseases; Cell Movement; Collagen; Disease Progression; Fibrin; Hemorrhage; Mice; Mice, Knockout; Urokinase-Type Plasminogen Activator

Increased risk of thrombosis, with propitious conditions for fibrin deposition, along with upregulation of inflammation, are important factors that enhance plaque formation in atherosclerosis. Evidence supporting the role of anticoagulant protein C (PC) as an inflammatory agent has emerged, supplementing its well-known function as an anticoagulant. Thus, we sought to examine whether a PC deficiency would lead to an enhanced response to an acute arterial hyperplasic challenge. The presentation of early arterial inflammation was studied using a copper/silicone arterial cuff model of accelerated focal neointimal remodeling in mice with a heterozygous total deficiency of PC (PC+/-). Increased inflammation, cell proliferation, cell migration, fibrin elevation, and tissue necrosis were observed in the treated arteries of PC+/- mice, as compared to arteries of equally challenged age- and gender-matched WT mice. These results indicate that PC+/- mice subjected to this challenge displayed enhanced focal arterial inflammation and thrombosis, leading to larger neointimas and subsequent localized occlusion, as compared to their WT counterparts.

Topics: Animals; Arteritis; Carotid Arteries; Carotid Artery Diseases; Cell Movement; Cell Proliferation; Copper; Disease Models, Animal; Fibrin; Fibrinogen; Mice; Mice, Transgenic; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Necrosis; Protein C; Protein C Deficiency; Time Factors; Tunica Intima

Unstable atherosclerotic plaques exhibit microdeposits of fibrin that may indicate the potential for a future rupture. However, current methods for evaluating the stage of an atherosclerotic lesion only involve characterizing the level of vessel stenosis, without delineating which lesions are beginning to rupture. Previous work has shown that fibrin-targeted, liquid perfluorocarbon nanoparticles, which carry a high payload of gadolinium, have a high sensitivity and specificity for detecting fibrin with clinical (1)H MRI. In this work, the perfluorocarbon content of the targeted nanoparticles is exploited for the purposes of (19)F imaging and spectroscopy to demonstrate a method for quantifiable molecular imaging of fibrin in vitro at 4.7 T. Additionally, the quantity of bound nanoparticles formulated with different perfluorocarbon species was calculated using spectroscopy. Results indicate that the high degree of nanoparticle binding to fibrin clots and the lack of background (19)F signal allow accurate quantification using spectroscopy at 4.7 T, as corroborated with proton relaxation rate measurements at 1.5 T and trace element (gadolinium) analysis. Finally, the extension of these techniques to a clinically relevant application, the evaluation of the fibrin burden within an ex vivo human carotid endarterectomy sample, demonstrates the potential use of these particles for uniquely identifying unstable atherosclerotic lesions in vivo.

Topics: Arteriosclerosis; Biotinylation; Carotid Artery Diseases; Contrast Media; Emulsions; Endarterectomy, Carotid; Fibrin; Fluorine; Gadolinium DTPA; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Nanostructures; Particle Size; Sensitivity and Specificity

Elevated plasma levels of plasminogen activator inhibitor type 1 (PAI-1) are associated with myocardial infarction, atherosclerosis, and restenosis. PAI-1 is increased in atherosclerotic arteries and failed vein grafts. No experimental data, however, support a causal relationship between elevated PAI-1 expression and vascular lesions. Paradoxically, data generated in PAI-1 knockout mice suggest that PAI-1 might decrease lesion formation after arterial injury and that PAI-1 gene transfer might prevent restenosis.. Using the rat carotid balloon injury model and a PAI-1-expressing adenoviral vector, we tested whether elevated arterial PAI-1 expression would alter neointima formation. Compared with control-transduced arteries, neointima formation in PAI-1-transduced arteries was initially retarded. By 14 days, however, the intimas of PAI-1-transduced arteries were significantly larger than intimas of control-transduced arteries (1.6+/-0.1x10(5) versus 1.2+/-0.1x10(5) micrometer(2), n=18 to 19, P<0.03). PAI-1 expression in individual arteries correlated with increased cell proliferation at 4 and 8 days after injury (R=0.6, P<0.02 and P<0.006). PAI-1 expression also correlated with fibrin(ogen) accumulation (R=0.77, P<0.001), and fibrin(ogen) accumulation correlated strongly with proliferation (R=0.86, P<0.00001).. Increased expression of PAI-1 in the artery wall promotes neointima growth after balloon injury. Therefore, despite encouraging data generated in other animal models, PAI-1 is not a promising agent for gene therapy to prevent restenosis. Moreover, our data associate elevated PAI-1 expression with fibrin(ogen) accumulation and increased cell proliferation. These data suggest a mechanism to explain the association between elevated PAI-1 expression and the progression of arterial disease.

Topics: Adenoviridae; Angioplasty, Balloon; Animals; Carotid Artery Diseases; Cell Division; Disease Models, Animal; Disease Progression; Fibrin; Genetic Vectors; Immunohistochemistry; Plasminogen Activator Inhibitor 1; Rats; Transduction, Genetic; Tunica Intima; Tunica Media

Dissolution of the fibrin blood clot is regulated in large part by plasminogen activator inhibitor-1 (PAI-1). Elevated levels of plasma PAI-1 may be an important risk factor for atherosclerotic vascular disease and are associated with premature myocardial infarction. The role of the endogenous plasminogen activation system in limiting thrombus formation following atherosclerotic plaque disruption is unknown. This study found that genetic deficiency for PAI-1, the primary physiologic regulator of tissue-type plasminogen activator (tPA), prolonged the time to occlusive thrombosis following photochemical injury to carotid atherosclerotic plaque in apolipoprotein E-deficient (apoE(-/-)) mice. However, anatomic analysis revealed a striking difference in the extent of atherosclerosis at the carotid artery bifurcation between apoE(-/-) mice and mice doubly deficient for apoE and PAI-1 (PAI-1(-/-)/apoE(-/-)). Consistent with a previous report, PAI-1(+/+)/apoE(-/-)and PAI-1(-/-)/apoE(-/-) mice developed similar atherosclerosis in the aortic arch. The marked protection from atherosclerosis progression at the carotid bifurcation conferred by PAI-1 deficiency suggests a critical role for PAI-1 in the pathogenesis of atherosclerosis at sites of turbulent flow, potentially through the inhibition of fibrin clearance. Consistent with this hypothesis, intense fibrinogen/fibrin staining was observed in atherosclerotic lesions at the carotid bifurcation compared to the aortic arch. These observations identify significant differences in the pathogenesis of atherosclerosis at varying sites in the vascular tree and suggest a previously unappreciated role for the plasminogen activation system in atherosclerosis progression at sites of turbulent flow. (Blood. 2000;96:4212-4215)

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Apolipoproteins E; Arteriosclerosis; Carotid Artery Diseases; Carotid Artery Injuries; Carotid Artery, Common; Carotid Stenosis; Disease Progression; Fibrin; Fibrinogen; Hemorheology; Male; Mice; Mice, Knockout; Photochemistry; Plasminogen; Plasminogen Activator Inhibitor 1

Mechanical denudation of the endothelium of the carotid artery in animals produces a nonocclusive thrombus, but the brains of these animals have not been examined for the presence of embolic stroke.. The endothelium of the right carotid artery of 16 Wistar rats was denuded using a balloon catheter. Phosphotungstic acid hematoxylin (PTAH) staining and scanning electron micrographs of the nonocclusive thrombi in the carotid arteries were compared with those produced by photochemical methods, and brains were examined for infarcts.. Although nonocclusive thrombi were present in the carotid arteries of 4 of 4 rats killed at 4 hours and in 8 of 12 killed at 24 hours, neither cerebral infarcts nor emboli were seen in the 14 brains evaluated by light microscopy. PTAH demonstrated a high fibrin content in the thrombus produced by the endothelial denudation, with almost no fibrin seen in photochemically induced thrombi. Scanning electron microscopy confirmed dense networks of fibrin in the thrombi produced by balloon denudation.. The composition of a nonocclusive thrombus may determine the embolic potential of this thrombus. A low fibrin content in a nonocclusive platelet thrombus may enhance the embolic potential. This suggests that platelet inhibition may also be indicated in patients with carotid artery disease who are being treated with anticoagulant.

Topics: Animals; Carotid Arteries; Carotid Artery Diseases; Endothelium, Vascular; Fibrin; Intracranial Embolism and Thrombosis; Male; Rats; Rats, Wistar; Thrombosis

The T2G1s monoclonal antifibrin antibody binds specifically to fibrin but not to fibrinogen.. In a canine model of acute arterial thrombosis, we determined the feasibility of imaging thrombi using a 99mTc-labeled Fab' fragment. In 14 dogs, 10 carotid and 13 femoral artery thrombi were produced using 2-hour temporary occlusion, crush injury, and local thrombin injection methods. A sham-operated carotid artery served as control. Antifibrin antibody was injected intravenously at the end of temporary occlusion. Serial planar radionuclide images were obtained immediately and at 1 and 2 hours. Following killing the dogs at 2 hours, we measured antibody uptake ex vivo in 5-mm-long segments of thrombus, the adjacent injured artery, and a control artery. Antibody was cleared from the blood with a mean +/- SD t1/2 of 121 +/- 23 minutes. The thrombi weighed 218 +/- 140 mg. Antibody uptake in the thrombi was patchy, and the thrombi were closely adherent to the injured arterial wall. In the segment with maximal ex vivo antibody uptake, the ratio of control artery to blood counts/g/sec was 0.65 +/- 0.46, the injured artery-to-blood ratio was 2.35 +/- 1.01 (p less than 0.0001 versus control), and the thrombus-to-blood ratio was 4.24 +/- 2.58 (p less than 0.0001 versus control). In three dogs, an isotype-matched ovarian tumor antibody labeled with 111In was injected with T2G1s but was not taken up in the thrombus or the adjacent arterial wall. Visual analysis of the in vivo carotid radionuclide images showed uptake by 2 hours in all 10 carotid thrombi. Quantitative image analysis, measured as the thrombus-to-opposite carotid artery ratio, showed increasing uptake over time with ratios of 1.1 +/- 0.3, 1.6 +/- 2.0, and 2.2 +/- 1.3 on the immediate, 1-hour, and 2-hour images, respectively. All quantitative ratios of 1.3 or greater were visually identified.. 99mTc-labeled Fab' fragments of the T2G1s antibody are taken up specifically by acute arterial thrombi after intravenous injection. Uptake is progressive over a 2-hour period, and all thrombi are detected by radionuclide imaging at 2 hours. These results show that it is feasible to noninvasively detect arterial thrombi within 2 hours of formation.

Topics: Animals; Antibodies, Monoclonal; Carotid Arteries; Carotid Artery Diseases; Dogs; Femoral Artery; Fibrin; Radionuclide Imaging; Technetium; Thrombosis

We evaluated 40 consecutive carotid endarterectomy specimens for the presence of fibrin. Intraplaque hemorrhage was noted in 93% of specimens. At the plaque surface, there were two patterns of fibrin distribution. Type I, suggesting a lumen thrombus, was found in 7 specimens. Type II, suggesting an intraplaque hemorrhage at the lumen surface, was found in 15 specimens. These changes were not significantly associated with the presence of ischemic symptoms or the use of antiplatelet or anticoagulant medications. All specimens with Type I change had arteriographic evidence of at least 70% diameter stenosis. The frequent lack of fibrin at the plaque surface suggests that there may be inherent limitations of standard medical treatment for carotid artery disease.

Topics: Arteriosclerosis; Carotid Arteries; Carotid Artery Diseases; Carotid Artery Thrombosis; Endarterectomy; Female; Fibrin; Hemorrhage; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prospective Studies

Four cases of high-flow carotid-cavernous sinus fistula (CCF), three of them posttraumatic and one spontaneous, have been treated by a direct surgical approach to the cavernous sinus. The CCF's were obliterated by the introduction into the cavernous sinus of muscle fragments and/or fibrin sealant. In the three cases with a preoperatively patent internal carotid artery (ICA), the CCF was occluded and the ICA flow preserved. One of these also had a posttraumatic false aneurysm that enclosed the two avulsed ends of a transected intracavernous ICA. This was treated by cervical ICA ligation following resolution of the CCF. A fourth patient, who had previously undergone an unsuccessful ICA trapping procedure elsewhere, also obtained a good result. The case histories and the surgical technique are presented. Direct intracavernous obliteration with muscle fragments and fibrin sealant fulfills the criteria for treatment of high-flow CCF's: occlusion of the arteriovenous fistula and preservation of the ICA circulation. While this surgical technique is a therapeutic option in some cases, it appears to have precise indications in others.

Topics: Adult; Arteriovenous Fistula; Carotid Artery Diseases; Cavernous Sinus; Female; Fibrin; Fibrin Tissue Adhesive; Humans; Male; Middle Aged

The author used a two-component adhesive (homologous fibrinogen and thrombin) to develop a medium with controllable rate and extent of setting and coagulation. After mixing with the radiopaque substance metrizamide, the material meets the criteria postulated for an endoarterial embolization medium: variable and controllable viscosity, elasticity after setting, absence of toxicity, radio-opacity, and adequate sterilizability. After setting, the fibrin medium is a clear, solid, but soft elastic substance clearly visible on the X-ray film even in fine structures.

Topics: Arteriovenous Fistula; Carotid Artery Diseases; Cavernous Sinus; Embolization, Therapeutic; Fibrin; Humans; Viscosity

Topics: Animals; Anti-Inflammatory Agents; Arteriosclerosis; Aspirin; Blood Platelets; Blood Vessels; Carotid Artery Diseases; Coronary Disease; Dipyridamole; Female; Fibrin; Humans; Male; Prostaglandins; Sex Factors; Sulfinpyrazone; Thrombosis

Clinical experiences in a timespan of two and a half years with a human fibrinogen concentrate in head and neck surgery are reported. In 49 patients with different bleeding disorders tonsillectomies, adenectomies and nasal dermoplasties (Osler's disease) were carried out. In these cases primary hemostasis due to the fibrin adhesive combined with an allogenic collagen implant could be obtained without any subsitution of the deficient blood clotting factors. In all these cases no complications could be observed. In other 193 cases which underwent a surgical treatment in the head and neck region (frontobasal and laterobasal fractures, rupture of the carotid artery, closure of perforations of the nasal septum and oroantral fistulas, different methods of skinmucosa- and nerve-grafting) the fibrin adhesive was successfully used.

Topics: Carotid Artery Diseases; Carotid Artery Injuries; Collagen; Fibrin; Head; Hemostasis; Humans; Nasal Septum; Neck; Nose Diseases; Oroantral Fistula; Rupture; Skin Transplantation; Skull Fractures; Tissue Adhesives; Tonsillectomy; Transplantation, Autologous; Tympanoplasty

Topics: Animals; Blood Coagulation Tests; Carotid Artery Diseases; Endopeptidases; Fibrin; Fibrinogen; Fibrinolytic Agents; Injections, Intravenous; Prothrombin; Rats; Snake Venoms; Thrombosis

Topics: Animals; Blood Platelets; Carotid Arteries; Carotid Artery Diseases; Carotid Artery Injuries; Electric Injuries; Fibrin; Male; Methods; Microscopy, Electron; Rabbits