fibrin and Constriction--Pathologic

The biophysics of blood flow can dictate the function of molecules and cells in the vasculature with consequent effects on hemostasis, thrombosis, embolism, and fibrinolysis. Flow and transport dynamics are distinct for (i) hemostasis vs. thrombosis and (ii) venous vs. arterial episodes. Intraclot transport changes dramatically the moment hemostasis is achieved or the moment a thrombus becomes fully occlusive. With platelet concentrations that are 50- to 200-fold greater than platelet-rich plasma, clots formed under flow have a different composition and structure compared with blood clotted statically in a tube. The platelet-rich, core/shell architecture is a prominent feature of self-limiting hemostatic clots formed under flow. Importantly, a critical threshold concentration of surface tissue factor is required for fibrin generation under flow. Once initiated by wall-derived tissue factor, thrombin generation and its spatial propagation within a clot can be modulated by γ'-fibrinogen incorporated into fibrin, engageability of activated factor (FIXa)/activated FVIIIa tenase within the clot, platelet-derived polyphosphate, transclot permeation, and reduction of porosity via platelet retraction. Fibrin imparts tremendous strength to a thrombus to resist embolism up to wall shear stresses of 2400 dyne cm(-2) . Extreme flows, as found in severe vessel stenosis or in mechanical assist devices, can cause von Willebrand factor self-association into massive fibers along with shear-induced platelet activation. Pathological von Willebrand factor fibers are A Disintegrin And Metalloprotease with ThromboSpondin-1 domain 13 resistant but are a substrate for fibrin generation due to FXIIa capture. Recently, microfluidic technologies have enhanced the ability to interrogate blood in the context of stenotic flows, acquired von Willebrand disease, hemophilia, traumatic bleeding, and drug action.

Topics: Animals; Blood Coagulation; Blood Flow Velocity; Blood Platelets; Constriction, Pathologic; Diffusion; Factor IXa; Factor VIIIa; Fibrin; Fibrinolysis; Hemostasis; Humans; Mice; Platelet Activation; Platelet Adhesiveness; Platelet-Rich Plasma; Polyphosphates; Porosity; Rheology; Stress, Mechanical; Thrombin; Thromboplastin; Thrombosis; von Willebrand Factor

Fibrin sheath formation around venous access devices (VADs) frequently leads to persistent withdrawal occlusion (PWO). PWO is a common problem encountered with VADs. Although PWO is often easily managed with small doses of thrombolytic therapy (e.g., urokinase), it could result in a more serious complication, such as chemotherapy extravasation. Careful assessment of all VADs is important to identify complications such as fibrin sheath formation, which can potentially lead to extravasation. To rule out fibrin sheath formation, catheter dye studies need to be obtained when fibrinolytic therapy has failed to restore catheter function. The purpose of this paper is to illustrate a retrospective case report demonstrating drug extravasation caused by the development of fibrin sheath formation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Catheterization, Central Venous; Catheters, Indwelling; Constriction, Pathologic; Cyclophosphamide; Equipment Failure; Extravasation of Diagnostic and Therapeutic Materials; Female; Fibrin; Humans; Infusions, Intravenous; Middle Aged; Paclitaxel; Plasminogen Activators; Urokinase-Type Plasminogen Activator

Formation of intravenous catheter-related thrombosis leads to central venous stenosis in patients requiring renal replacement therapy or chemotherapy infusion, yet the triggers or mechanisms remain unclear, especially in patients without symptoms of infection. In this study, we found that neutrophil extracellular traps (NETs) could be detected in the fibrin sheaths from dialysis patients without clinical manifestations of infection. Confocal microscopy revealed bacteria imbedded in NETs in the fibrin sheaths. Thirty-nine of 50 (78%) fibrin sheath specimens contained bacteria detectable by 16S ribosomal RNA genome typing with a predominance of

Topics: Animals; Bacteremia; Catheters, Indwelling; Constriction, Pathologic; Extracellular Traps; Fibrin; Neutrophils; Rats; Staphylococcus aureus; Thrombosis; Venous Thrombosis

The efficacy of thrombolysis is inversely correlated with thrombus age. During early thrombogenesis, activated factor XIII (FXIIIa) cross-links α2-AP to fibrin to protect it from early lysis. This was exploited to develop an α2-AP-based imaging agent to detect early clot formation likely susceptible to thrombolysis treatment. In this study, this imaging probe was improved and validated using 111In SPECT/CT in a mouse thrombosis model. In vitro fluorescent- and 111In-labelled imaging probe-to-fibrin cross-linking assays were performed. Thrombus formation was induced in C57Bl/6 mice by endothelial damage (FeCl3) or by ligation (stenosis) of the infrarenal vena cava (IVC). Two or six hours post-surgery, mice were injected with 111In-DTPA-A16 and ExiTron Nano 12000, and binding of the imaging tracer to thrombi was assessed by SPECT/CT. Subsequently, ex vivo IVCs were subjected to autoradiography and histochemical analysis for platelets and fibrin. Efficient in vitro cross-linking of A16 imaging probe to fibrin was obtained. In vivo IVC thrombosis models yielded stable platelet-rich thrombi with FeCl3 and fibrin and red cell-rich thrombi with stenosis. In the stenosis model, clot formation in the

Topics: Animals; Constriction, Pathologic; Disease Models, Animal; Fibrin; Mice; Mice, Inbred C57BL; Thrombosis; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Venous Thrombosis

The development of venous thromboembolism (VTE) is associated with high mortality among gastric cancer (GC) patients. Neutrophil extracellular traps (NETs) have been reported to correlate with the prothrombotic state in some diseases, but are rarely reported in GC patients.. To investigate the effect of NETs on the development of cancer-associated thrombosis in GC patients.. The levels of NETs in blood and tissue samples of patients were analyzed by ELISA, flow cytometry, and immunofluorescence staining. NET generation and hypercoagulation of platelets and endothelial cells (ECs). NETs were likely to form in blood and tissue samples of GC patients compared with healthy individuals.. GC-induced NETs strongly increased the risk of VTE development both

Topics: Animals; Constriction, Pathologic; Endothelial Cells; Extracellular Traps; Fibrin; Mice; Neutrophils; Stomach Neoplasms; Thrombophilia; Thrombosis; Venous Thromboembolism

A novel stent retriever device for in vivo mechanical thrombectomy for acute cerebral infarction has been developed. In this study, we compared the thrombus removal capacity, potential complications, and extent of vessel wall damage of this novel device with those of the Solitaire FR device by performing a histopathologic analysis using an autopsied canine model. Through this experimental evaluation, we aimed to assess the safety and efficacy of the newly developed thrombus removal device for cerebral infarction. Blood clots (autologous thrombus) were injected into 12 canines. Mechanical thrombectomy was performed in six canines using the newly developed Tromba thrombectomy device (experimental group) and in the other six canines using the Solitaire FR thrombectomy device (control group). Angiographic and histopathologic evaluations were performed 1 month after the blood vessels underwent mechanical thrombectomy. In the experimental group, the reperfusion patency was classified as "no narrowing" in five cases and "moderate narrowing (25%-50% stenosis)" in one case. In the control group, the reperfusion patency was classified as "no narrowing" in four cases, "moderate narrowing (25%-50% stenosis)" in one case, and "slight narrowing (less than 25% stenosis)" in one case. In the experimental group, intimal proliferation was observed in only two cases, endothelial loss was observed in two cases, and device-induced medial injury was observed in one case. In the control group, intimal proliferation was observed in two cases, endothelial loss was observed in one case, and thrombosis (fibrin/platelet) was observed in one case. The Tromba thrombectomy device showed no significant difference to the conventional Solitaire device in angiographic and histopathologic evaluations after thrombus removal. The stability and efficiency of the newly developed Tromba device are considered to be high and comparable to those of Solitaire.

Topics: Animals; Cerebral Infarction; Constriction, Pathologic; Dogs; Fibrin; Stents; Stroke; Thrombectomy; Thrombosis; Treatment Outcome

Quantitative relationships between the extent of injury and thrombus formation in vivo are not well understood. Moreover, it has not been investigated how increased injury severity translates to blood-flow modulation. Here, we investigated interconnections between injury length, clot growth, and blood flow in a mouse model of laser-induced thrombosis. Approach and Results: Using intravital microscopy, we analyzed 59 clotting events collected from the cremaster arteriole of 14 adult mice. We regarded injury length as a measure of injury severity. The injury caused transient constriction upstream and downstream of the injury site resulting in a 50% reduction in arteriole diameter. The amount of platelet accumulation and fibrin formation did not depend on arteriole diameter or deformation but displayed an exponentially increasing dependence on injury length. The height of the platelet clot depended linearly on injury length and the arteriole diameter. Upstream arteriolar constriction correlated with delayed upstream velocity increase, which, in turn, determined downstream velocity. Before clot formation, flow velocity positively correlated with the arteriole diameter. After the onset of thrombus growth, flow velocity at the injury site negatively correlated with the arteriole diameter and with the size of the above-clot lumen.. Injury severity increased platelet accumulation and fibrin formation in a persistently steep fashion and, together with arteriole diameter, defined clot height. Arterial constriction and clot formation were characterized by a dynamic change in the blood flow, associated with increased flow velocity.

Topics: Abdominal Muscles; Animals; Arterioles; Blood Coagulation; Blood Flow Velocity; Blood Platelets; Constriction, Pathologic; Disease Models, Animal; Fibrin; Intravital Microscopy; Male; Mice; Microscopy, Fluorescence; Severity of Illness Index; Thrombosis; Time Factors; Vascular System Injuries

Covered stents have been demonstrated to reduce restenosis; however, the membrane's limited biocompatibility can still lead to thrombus formation. To obtain optimal surface hemocompatibility, endothelialization of the luminal surface has been proposed. However, the effect of delivery procedures, such as crimping and balloon dilatation, on the endothelial layer has not been quantified. This study investigated the impact of such procedures on endothelialized covered stents in vitro.. Using an injection molding technique, bare metal stents were covered with fibrin subsequently, endothelialized and conditioned in a bioreactor under arterial pressure (80-120 mmHg) and shear stress (1 Pa). For each set of experiments, three covered stents were prepared, one being subjected to crimping alone, one to crimping followed by balloon dilatation and one serving as control. The experiment was repeated three times. The endothelial coverage was quantified by scanning electron microscopy (SEM). The functionality of the endothelium after exposure to platelet-rich plasma was evaluated by immunohistochemistry and SEM.. The mean endothelial coverage of control, crimped, crimped and balloon-dilated stents was 87.6, 80.1 and 52.1%, respectively, indicating that endothelial cells detached significantly not after crimping (P = 0.465) but following balloon dilatation (P < 0.001). The cells present on the stent's surface, either after crimping or crimping followed by balloon dilatation, expressed eNOS and CD31 and exhibited no platelet adhesion.. The simulated delivery procedure resulted in the retention of viable cells on more than half of the luminal surface. The main damage to the layer occurred during balloon dilatation.

Topics: Alloys; Angioplasty, Balloon; Animals; Biocompatible Materials; Constriction, Pathologic; Dilatation; Endothelium, Vascular; Fibrin; Gels; Humans; In Vitro Techniques; Microscopy, Electron, Scanning; Models, Cardiovascular; Self Expandable Metallic Stents; Thrombosis

This study sought to compare the effect of paclitaxel-coated balloon (PCB) concentration on tissue levels and vascular healing using 3 different PCB technologies (In.Pact Pacific = 3 μg/mm(2), Lutonix = 2 μg/mm(2) and Ranger = 2 μg/mm(2)) in the experimental setting.. The optimal therapeutic dose for PCB use has not been determined yet.. Paclitaxel tissue levels were measured up to 60 days following PCB inflation (Ranger and In.Pact Pacific) in the superficial femoral artery of healthy swine (18 swine, 36 vessels). The familial hypercholesterolemic swine model of superficial femoral artery in-stent restenosis (6 swine, 24 vessels) was used in the efficacy study. Two weeks following bare-metal stent implantation, each in-stent restenosis site was randomly treated with a PCB or an uncoated control balloon (Sterling). Quantitative vascular analysis and histology evaluation was performed 28 days following PCB treatment.. All PCB technologies displayed comparable paclitaxel tissue levels 4 h following balloon inflation. At 28 days, all PCB had achieved therapeutic tissue levels; however, the In.Pact PCB resulted in higher tissue concentrations than did the other PCB groups at all time points. Neointimal inhibition by histology was decreased in all PCB groups compared with the control group, with a greater decrease in the In.Pact group. However, the neointima was more mature and contained less peri-strut fibrin deposits in both 2-μg/mm(2) PCB groups.. Compared with the clinically established PCB dose, lower-dose PCB technologies achieve lower long-term tissue levels but comparable degrees of neointimal inhibition and fewer fibrin deposits. The impact of these findings in restenosis reduction and clinical outcomes needs to be further investigated.

Topics: Animals; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Disease Models, Animal; Endovascular Procedures; Femoral Artery; Fibrin; Hyperlipoproteinemia Type II; Metals; Neointima; Paclitaxel; Peripheral Arterial Disease; Radiography; Stents; Swine; Tissue Distribution; Vascular Access Devices; Wound Healing

To evaluate the effect of a polymer-free Biolimus A9-eluting stent [BioFreedom (BF)], compared with that of a biodegradable polymer-based Biolimus A9-eluting stent [BioMatrix Flex (BMF)] and a bare metal stent (BMS) in balloon denuded and radiated hypercholesterolemic rabbit iliac arteries.. Rabbits were fed with 1% cholesterol diet (n = 14) for 14 days, both iliac arteries were balloon denuded and radiated, and then rabbits were switched to 0.15% cholesterol diet. After 4 weeks, BF (n = 8), BMF (n = 8), and BMS (n = 8) were deployed in denuded and radiated areas. Four weeks later animals were euthanized, arterial segments were processed for morphometry.. The neointimal area in vessels implanted with BF stents was significantly less than that seen in vessels implanted with BMS (0.90 mm(2) ± 0.14 vs. 1.29 mm(2) ± 0.23, P <0.01). Percent fibrin and fibrin score were higher with BMF stents compared to BMS (P <0.03 and <0.04) and giant cell number was significantly higher with both BMF and BF stents (P < 0.01 for both). Percent endothelialization was significantly higher and % uncovered struts were lower with BMS compared to either BMF or BF stents (P < 0.05 for both).. This study demonstrates that compared to BMS, BF stents significantly decreased neointimal hyperplasia.

Topics: Absorbable Implants; Angioplasty, Balloon; Animals; Atherosclerosis; Cardiovascular Agents; Constriction, Pathologic; Disease Models, Animal; Drug-Eluting Stents; Fibrin; Hypercholesterolemia; Hyperplasia; Iliac Artery; Inflammation; Male; Metals; Neointima; Plaque, Atherosclerotic; Polymers; Prosthesis Design; Rabbits; Sirolimus; Stents; Time Factors

Peripheral nerve injury is followed by Wallerians degeneration (WD) and degradation and regeneration of the extracellular matrix (ECM) are very important events in these processes. We tested fibrinolytic activities and the expression level of tPA and uPA levels in chronic constriction injury (CCI) model. The presented data demonstrates that in the injury nerve of CCI model, the fibrinolytic activities is upregulated and main caused by the upregulation of tPA expression. We also find that the activities of tPA and MMP-9 are co-upregulated post-CCI, both at CCI site and proximal site. These results indicate that tPA activity may regulate the MMP-9 activity in injury nerve post-CCI.

Topics: Animals; Constriction, Pathologic; Fibrin; Male; Matrix Metalloproteinase 9; Pain; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Tissue Plasminogen Activator; Up-Regulation; Urokinase-Type Plasminogen Activator

Topics: Blood Vessels; Constriction, Pathologic; Drug-Eluting Stents; Fibrin; Humans; Hypersensitivity; Myocardial Infarction; Patient Selection; Platelet Aggregation Inhibitors; Prosthesis Design; Risk Factors; Thrombosis; Wound Healing

Topics: Catheterization, Central Venous; Constriction, Pathologic; Drug-Related Side Effects and Adverse Reactions; Fibrin; Humans; Peripheral Vascular Diseases; Prognosis; Vena Cava, Superior; Venous Thrombosis

To determine the incidence of pericatheter sleeve formation, thrombus formation, and stenosis of the central veins in hemodialysis patients with temporary catheters.. In this prospective study, 57 patients (40 males, 17 females) with temporary dialysis catheters had catheter venography by pulling back the catheter just before removal. Patient's age range was 25-87 years (mean age, 51 years). The venographic studies were evaluated for pericatheter sleeve formation, thrombus formation, and stenosis of the brachiocephalic vein (BCV) and the superior vena cava (SVC). The IJV could only be evaluated if there was adequate filling during contrast administration. In a subgroup of patients who had had only right IJV or only right SCV catheters, impact of these catheters on the central veins was compared.. The catheter location was right internal jugular vein (IJV) in 26 cases, right subclavian vein (SCV) in 27 cases, left IJV in 1 case, and left SCV in 3 cases. Thirty-two patients (56%) had had only one temporary catheter and the rest had had more than one inserted. The mean dwell time for the catheters was 21 days (range 7-59 days). A pericatheter sleeve was detected on venography in 32 (56%) patients and thrombus formation was noted in 16 patients (28%). A total of 41 patients (72%) exhibited pericatheter sleeve and/or thrombus formation. While 19 of the 32 patients (59%) without previous catheterization had a sleeve around the catheter, only 13 (52%) of 25 patients who had had multiple catheters inserted had a sleeve (P > 0.005). Of the eight patients (14%) with BCV stenosis, two had >50% stenosis. Only one patient (2%) had mild stenosis of the SVC. Three patients out of 15 (20%) who had diagnostic venography for the IJV had severe stenosis of the vein. Pericatheter sleeve formation was more frequent in women (P < 0.005). However, there were no statistical differences with respect to pericatheter sleeve formation, luminal filling defect and BCV stenosis when patients were grouped according to age, dwell time of the catheter, number of catheters inserted, and diameter of the SVC. Forty-two of the fifty-seven patients had had only right IJV (n =16) or right SCV (n = 26) catheters. There were no differences between these groups with respect to rates of pericatheter sleeve formation, thrombus formation, or BCV stenosis.. This study showed that even short-term catheters result in significantly high rates of pericatheter sleeve and thrombus formation which are two of the important causes of catheter malfunction. The IJV route is known to be much safer than the SCV route with respect to stenosis formation in the vein in which the catheter is inserted; however, the result showed no differences between the two routes with respect to frequencies of pericatheter sleeve formation, thrombus formation, and BCV stenosis. These findings remind us again that we should avoid unnecessary catheter insertion even for short-term in these chronically ill patients.

Topics: Adult; Aged; Aged, 80 and over; Brachiocephalic Veins; Catheterization, Central Venous; Catheters, Indwelling; Constriction, Pathologic; Contrast Media; Female; Fibrin; Foreign Bodies; Humans; Jugular Veins; Male; Middle Aged; Phlebography; Prospective Studies; Renal Dialysis; Sex Factors; Subclavian Vein; Time Factors; Vena Cava, Superior; Venous Thrombosis

Most animal models of venous thrombosis involve acute thrombosis with hypercoagulability in small rodents. To better replicate human disease, we developed two models in the pig, a species similar to humans in size and in vascular and coagulation reactivity. One model involves de-endothelialisation with 50% or 80% stenosis and the other replacement of a venous segment by a Gore-Tex vascular prosthesis. Both models were tested with and without acute induced hypercoagulability (thromboplastin infusion). Thrombi obtained without thromboplastin infusion were composed of a multilayered platelet and a fibrin meshwork structure similar to that usually found in humans. With thromboplastin infusion, the thrombi were homogeneous fibrin structures imprisoning red blood cells. The high incidence of thrombosis obtained with the 80% stenosis model would be useful for studying anticoagulant treatments, whereas the low incidence with 50% stenosis would be useful for evaluating procoagulant effects of conditions or treatments. These new models shed further light on the development of venous thrombi under conditions similar to those seen in humans and may prove useful for investigating anticoagulant and procoagulant effects.

Topics: Animals; Blood Vessel Prosthesis; Chronic Disease; Constriction, Pathologic; Disease Progression; Endothelium, Vascular; Fibrin; Hemorheology; Jugular Veins; Models, Animal; Swine; Thrombophilia; Thromboplastin; Venous Thrombosis

Topics: Animals; Aorta; Arterial Occlusive Diseases; Arteries; Blood Cells; Carotid Artery Injuries; Catheterization; Constriction, Pathologic; Fibrin; Immunohistochemistry; Rabbits; Rats; Rats, Wistar; Time Factors

The stentless xenograft with its favorable hemodynamic performance on the left side of the heart seems an attractive, readily available alternative for the reconstruction of the right ventricular outflow tract in children.. To assess its function in a preclinical animal investigation, we replaced the pulmonary root with a Freestyle stentless aortic xenograft in 18 piglets of 26.6 +/- 3.2 kg weight. The animals were allowed to grow as much as possible and slaughtered when symptoms of heart failure developed or body weight reached more than 160 kg. All valve explants were analyzed by gross examination and photography and, in 4 representative pigs, by histologic examination.. Fourteen animals died prematurely after 2 weeks to 11 months. Twelve xenograft explants showed thick, immobilized, large nodular structures as cuspal remnants causing significant stenosis. At microscopy, large cuspal masses of degenerating collagen and fibrin and various inflammatory cells were frequently found. In the growing pig, most of the xenografts implanted in the pulmonary position showed early degeneration causing severe stenosis.. Use of this valve for right ventricular outflow tract reconstruction in children cannot be recommended.

Topics: Animals; Aortic Valve; Bioprosthesis; Body Weight; Calcinosis; Cardiac Output, Low; Cause of Death; Collagen; Constriction, Pathologic; Disease Models, Animal; Endocarditis; Fibrin; Growth; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Prosthesis Design; Prosthesis Failure; Pulmonary Valve; Surface Properties; Swine

Atherosclerotic plaque rupture may trigger the formation of mural thrombus. This thrombus formation is apparently affected by very high and complex shear conditions introduced by the luminal narrowing (stenosis) of the atheroma. To study the impact of such blood flow behaviour on thrombus formation we employed a model system where collagen-induced thrombogenesis is studied at the apex of well-defined eccentric stenoses. Thrombus formation in non-anticoagulated human blood drawn directly from an antecubital vein over the collagen coated stenosis apex for periods of 0.5, 1, 3 or 5 min was quantified by morphometry. The stenoses reduced the cross-sectional area of the blood flow channel by 60, 80 and 89%, which corresponded to apex wall shear rates of 2600, 10,500 and 32,000 s-1, respectively. Platelet-collagen adhesion decreased by increasing shear at the stenosis apex. The corresponding adhesion rates were highest at 1 min, then they gradually decreased upon prolongation of the perfusion time. The platelet thrombus volume increased in concert with increasing shear rate up to 10,500 s-1, whereas, at 32,000 s-1, the volume wa decreased. The corresponding growth rates and rates of thrombus occlusion at the apex levelled off at 3 min. Significant fibrin deposition was not observed before 3 min, and was most pronounced at 10,500 and 32,000 s-1. The plasma levels of fibrinopeptide A and beta-thromboglobulin increased in concert with increasing shear and perfusion time, particularly at the two highest shear conditions. Thus, hallmarks of thrombus formation at these stenoses with increasing shear are decreased platelet-collagen adhesion, and increased platelet-platelet interaction and fibrin deposition. A fibrin tail downstream to the collagen-attached platelet thrombus is regularly observed when thrombus occlusion exceeds 40%. However, the reduced thrombus growth at the most occlusive stenosis (89%) is presumably due to the high shear stresses which may reduce the rate of platelet incorporation into the thrombus and/or tear off thrombus fragments.

Topics: Analysis of Variance; Arteriosclerosis; beta-Thromboglobulin; Case-Control Studies; Collagen; Constriction, Pathologic; Fibrin; Fibrinopeptide A; Humans; Kinetics; Platelet Adhesiveness; Regional Blood Flow; Stress, Mechanical; Thrombosis

Balloon dilation is disappointing in maintaining patency of the arterial duct. In neonatal lambs, stent implantation in the arterial duct results in significantly larger ducts with greater pulmonary blood flow than balloon dilation. Little is known, however, about the duration of duct patency after stent implantation. The outcome of stent implantation into the arterial duct in 12 lambs was observed over a period of 1 to 24 months. Stents (Wallstent in 9, Tower stent in 3) were implanted after recanalizing the occluded duct at 2 to 7 days of age. Heparin was given only during the procedure, but no further anticoagulants were used. Angiographic or postmortem evaluations were made at 1, 1.5, 2, 3, 4, 6, 12, 16, and 21 months in a subgroup of 9 lambs who did not undergo reinterventions. The duct was patent in all these except for one studied at 16 months. Neointima initially developed in the center of the stent before extending toward the orifices, eventually burying the metal strands in contact with the wall. From 4 to 6 months onward stenoses were present inside some of the stents. When the stent did not protrude into the aorta, neointima extended over the duct orifice. Metal strands that were not in contact with the duct wall were incompletely covered with endothelial cells, platelets, and fibrin strands, but no thrombi were noted. Late balloon dilation of the stented duct was performed in two lambs increasing the pulmonary artery blood flow. In one lamb the neointimal lining was successfully removed at 14 months with an atherectomy catheter. Stent implantation into the arterial duct can maintain patency up to 21 months and could be considered as an alternative to neonatal systemic to pulmonary artery shunt operations. Neointimal proliferation and stenosis formation, however, is a major limitation that may eventually lead to a reduction in the pulmonary artery blood flow.

Topics: Animals; Animals, Newborn; Anticoagulants; Aorta; Atherectomy; Blood Platelets; Catheterization; Constriction, Pathologic; Ductus Arteriosus, Patent; Endothelium, Vascular; Equipment Design; Fibrin; Follow-Up Studies; Heparin; Pulmonary Artery; Radiography; Regional Blood Flow; Sheep; Stents; Thrombosis; Treatment Outcome; Tunica Intima; Vascular Patency

Cigarette smoking is a known risk factor for cardiovascular disease in men and women, and it has been suggested that this risk is linked to enhanced formation of platelet thromboxane A2 (TxA2). This led us to investigate the effect of cigarette smoking and TxA2 formation on collagen-induced thrombogenesis in flowing nonanticoagulated human blood. Thrombus formation in blood from smokers and nonsmokers was compared before and 2 hours after ingestion of a single oral dose of 990 mg aspirin, which is sufficient to block platelet TxA2 formation. Nonanticogulated blood was drawn directly from an antecubital vein over collagen fibrils in a parallel-plate perfusion chamber by a peristaltic roller pump placed distally to the chamber. Wall shear rates at the collagen surface were characteristic for medium-sized (650 s-1) and moderately stenosed (2600 s-1) arteries. Blood-collagen interactions were morphologically quantified, and markers of platelet release, beta-thromboglobulin (beta-TG), and activation of coagulation, fibrinopeptide A (FPA), were measured immediately distal to the perfusion chamber. The thrombus volume in blood from cigarette-smoking individuals was nearly twofold larger than in blood from nonsmokers at 2600 s-1 (37.4 and 19.4 microns 3/microns 2; P < .03). However, ingestion of aspirin reduced the thrombus volume in blood from smokers by 61.8% (P < .01), which was substantially more than the 37.6% reduction in blood from nonsmokers (P < .03). Neither cigarette smoking nor aspirin ingestion affected thrombus formation at 650 s-1. The plasma levels of FPA and beta-TG were slightly lower in nonsmokers and after aspirin ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Arteries; Aspirin; beta-Thromboglobulin; Blood Platelets; Cell Adhesion; Collagen; Constriction, Pathologic; Female; Fibrin; Fibrinopeptide A; Hematocrit; Humans; Male; Middle Aged; Platelet Count; Smoking; Thrombosis

A number of thrombotic mediators have been related to peripheral arterial disease in both epidemiological and pathological studies.. We measured preoperative levels of fibrinogen, cross-linked fibrin degradation products (FDP), and the endothelial markers, von Willebrand factor (vWF), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI), in the venous blood of 43 claudicants undergoing percutaneous transluminal angioplasty (PTA). Samples were repeated 4 months later, and changes in the levels of thrombotic mediators were compared with ten controls undergoing angiography alone. Additional perilesional arterial samples were obtained from 11 of the patients.. Arterial sampling indicated that successful PTA led to an immediate fall in tPA levels and a rise in arterial vWF (p < 0.05), together with a trend toward a significant rise in cross-linked FDP levels. Only the increase in FDP following successful PTA (36 cases) (p < 0.05) was observed in 4-month postangioplasty venous samples, whereas all variables remained unchanged in cases of restenosis (4 patients) and in controls (all comparisons made by Wilcoxon matched pairs test).. These findings suggest that successful PTA in patients with intermittent claudication results in acute endothelial disturbance and increased fibrin turnover at the site of angioplasty and in sustained increases in fibrin turnover (as reflected by FDP levels). The observation that this increase in fibrin turnover is absent in cases of restenosis within 4 months of PTA merits further study to determine whether increases in fibrin turnover are necessary to maintain patency following PTA.

Topics: Angioplasty, Balloon; Arterial Occlusive Diseases; Constriction, Pathologic; Endothelium, Vascular; Female; Femoral Artery; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Iliac Artery; Intermittent Claudication; Male; Plasminogen Inactivators; Popliteal Artery; Tissue Plasminogen Activator; von Willebrand Factor

Microscopical examination of 50 placentas of stillborn infants and 50 of normal infants (controls) was performed for detection of thrombosis in the stem fetal vessels. Fresh fibrin thrombi occurred with equal frequency in stillborns and normal infants, suggesting that these thrombi are not necessarily of pathological significance. In normal infants they might be related to clamping of the umbilical cord. In placentas of normal infants and of stillbirths with 1 day of placental retention (P.R.) organizing thrombi were rare and when occlusive they were related to avascular villi, which suggests that they were pre-mortem in origin. By contrast organizing thrombi were found in 78.5% of placentas of stillbirths with 2-7 days of P.R, where arterial occlusive thrombi were rarely associated with avascular villi. With over 7 days of P.R. they were almost fully organized. These findings suggest that most organizing thrombi in placental vessels of macerated stillbirths are probably post-mortem clots in process of organization by the still living placenta and should therefore not be attached pathological significance.

Topics: Constriction, Pathologic; Female; Fetal Death; Fibrin; Humans; Placenta; Pregnancy; Thrombosis

We studied the role of von Willebrand factor in coronary thrombosis in normal, heterozygous, and homozygous von Willebrand's disease pigs by producing coronary stenosis with a Goldblatt clamp positioned around the left anterior descending coronary artery. Flow velocity was assessed by a 20-MHz Doppler velocity probe distal to the Goldblatt clamp. Myocardial extracellular potassium levels were measured by potassium-sensitive electrodes in myocardium supplied by the left anterior descending artery. Whereas stenosis sufficient to block reactive hyperemia to a 20-second occlusion produced an elevation of myocardial extracellular potassium, it produced neither spontaneous cyclic flow reductions nor permanent cessation of coronary blood flow velocity. Injury of the coronary artery at the stenosis site with spring-loaded forceps produced cyclic flow reductions or permanent cessation of flow in eight of nine phenotypically normal pigs. On the other hand, flow variations occurred in none of the 10 von Willebrand's disease pigs, including four given purified von Willebrand factor at a dose that failed to correct the bleeding time (p less than 0.001, chi 2 test). Permanent cessation of flow was caused by an occlusive platelet-fibrin-red-blood-cell thrombus. Scanning electron micrographs from pigs with cyclic flow variations and from von Willebrand's disease pigs showed injured endothelium covered by adherent platelets, red and white blood cells, and fibrin. These data suggest an important role of native von Willebrand factor in sudden occlusive arterial thrombosis following stenosis and intimal injury.

Topics: Animals; Blood Flow Velocity; Constriction; Constriction, Pathologic; Coronary Circulation; Coronary Disease; Coronary Vessels; Fibrin; Microscopy, Electron, Scanning; Myocardium; Platelet Aggregation; Potassium; Swine; von Willebrand Diseases; von Willebrand Factor

A radioimmunoassay (RIA) has been set up using purified human melanoma tissue plasminogen activator and a specific antiserum raised against it. Concentration of antigen in citrated plasma of resting human subjects was found to be 7.1 +/- 1.6 ng/ml (mean +/- S.D.) while the lower limit of sensitivity of the RIA was 2 ng/ml. After venous occlusion or DDAVP infusion the levels of antigen were invariably elevated and a significant increase in the proportion of antigen having fibrin binding properties was observed. Decay studies in vitro and gel filtration of post-stimulus plasma indicated that the RIA detects active and inactive forms of antigen and the possible nature of the inactive antigen is discussed.

Topics: Arm; Chromatography, Gel; Constriction, Pathologic; Deamino Arginine Vasopressin; Fibrin; Fibrinolysis; Hemostatics; Humans; Infusions, Parenteral; Male; Peripheral Vascular Diseases; Radioimmunoassay; Reproducibility of Results; Tissue Plasminogen Activator

Intravascular coagulation in the rat kidney was induced by intravenous infusion of thrombin for 1 hr. The proximal tubular free-flow (Pt) and stop-flow (Psf) pressures were measured by micropuncture. Some proximal tubules were obstructed with solid paraffin before infusion of thrombin. In certain rats saralasin or indomethacin was administered for 1 hr starting 30 min after the thrombin infusion, and the effect on the tubular pressures was studied. The deposition of fibrin in the glomeruli was examined by light and electron microscopy. Pt fell from 15 +/- 1 (SE) to 7 +/- 2 mm Hg (P less than 0.05) during the infusion of thrombin. After a brief period of increased pressure the Psf fell rapidly from 37 +/- 1 to 17 +/- 1 mm Hg (P less than 0.05). In the previously obstructed nephrons the pressure (Po) increased parallel to the increase in Psf but remained elevated after the infusion of thrombin, 54 +/- 2 mm Hg. The arterial blood pressure (Pa) increased from 119 +/- 2 to 138 +/- 3 mm Hg (P less than 0.05). Saralasin raised the Psf from 15 +/- 1 to 19 +/- 1 mm Hg (P less than 0.05) but had no effect on Pt, Po, or Pa. Indomethacin did not influence the pressures. Morphological examination revealed fibrin in all glomeruli of normal nephrons. In the previously obstructed nephrons the deposition of fibrin was almost totally prevented. The results suggest that glomerular filtration is important for deposition of fibrin in the kidney.

Topics: Animals; Blood Coagulation; Constriction, Pathologic; Fibrin; Indomethacin; Kidney; Kidney Glomerulus; Kidney Tubules; Male; Pressure; Rats; Rats, Inbred Strains; Saralasin; Thrombin