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1.
目的探讨纤溶酶溶解血凝块的最佳时间及浓度。方法采集日本白兔股动脉血,应用模拟脑出血微创穿刺体外实验模型,采用5×5拉丁方设计,分析纤溶酶浓度(25 U/ml、50 U/ml、100 U/ml、200 U/ml及300 U/ml)、用药时机(抽血后2、4、6、8、16 h)和溶凝时间(给予纤溶酶后2、4、6、8、10 h)对体外血肿溶凝的时效和量效的影响。抽取兔股动脉血5 ml制备血凝块,实验管加相应浓度的纤溶酶0.2 ml,对照管加0.2 ml生理盐水,在各个时间点测定血凝块质量。结果兔动脉血实验数据结果显示,25 U/ml组(=8.496 mg)的溶凝质量明显低于50 U/ml组(=28.770 mg)、100 U/ml组(=38.904 mg)、200 U/ml组(=34.080 mg)、300 U/ml组(=28.324 mg),组间比较,差异有统计学意义[(B、C、D、E)>LSR_(0.05),P<0.05],而后4组间比较,差异均无统计学意义(P>0.05)。用药时机和溶凝时间对溶凝质量的影响,组间比较,差异均无统计学意义(F=0.62,P>0.05;F=1.44,P>0.05)。结论纤溶酶溶凝的最佳有效浓度为50 U/ml,延迟16 h用药不影响溶凝效果,溶凝2 h足以发挥作用。  相似文献   

2.
The detection of thrombi in rabbits has been investigated with 131I-labelled DD-3B6/22, a monoclonal antibody (Mab) reactive at high affinity (Kd = 2.68 x 10(-10) M) with human D Dimer (DD). DD-3B6/22 bound well to both "fresh" and "aged" human clots in an in vitro assay but showed poor binding to rabbit clots. However, reactivity was restored to rabbit blood if it was seeded, before clotting, with human DD covalently coupled to Sepharose beads. Thus, a rabbit model was developed in which blood was allowed to clot around DD-Sepharose beads introduced into the jugular vein. Gamma camera imaging showed that intact 131I-labelled DD-3B6/22 localised to these clots within 24 h. Uptake at this time was 0.202 +/- 0.012% injected dose per gram (%ID/g) compared with 0.086 +/- 0.018%ID/g after injection of control antibody. 131I-labelled F(ab')2 fragments of DD-3B6/22 allowed earlier scintigraphic detection of the clot which was evident 4 h after injection. Uptake in the clot at 24 h was 0.154 +/- 0.038 %ID/g compared with 0.109 +/- 0.027 %ID/g for a control F(ab')2. As antigen levels in the clot are estimated to be less than 300 micrograms DD, thus representing a very small human clot, the DD-3B6/22 Mab would appear to have a good potential for the sensitive detection of thrombi in a clinical setting.  相似文献   

3.
Indium-111-labeled monoclonal antibody 64C5 specific for the beta-chain of fibrin monomer was used to image canine (n = 6) experimental pulmonary emboli (at least one barium-thrombin and one copper-coil induced clot per dog). Uptake of 111In-64C5 and 125I-control-DIG26-11 were compared in 10 clots (7 barium-thrombin and 3 copper-coil) identified in the lungs. There was no difference in the blood clearance of 111In-64C5 and 125I-DIG26-11. Uptake of 111In-64C5 (0.183 +/- 0.105, mean %ID/g) was greater than 125I-DIG26-11 (0.024 +/- 0.025) in pulmonary clots (p less than 0.001). Mean thrombus to blood ratios at 24 hr were 6.78:1 for 64C5 and 0.57:1 for DIG26-11. The clots visualized in vivo were larger (0.315 +/- 0.381 g) than clots not visualized (0.089 +/- 0.098). Negative images were recorded in three dogs with pulmonary emboli, injected with 111In-labeled control monoclonal antibody 3H3. These data suggest that 111In-labeled antifibrin can detect large pulmonary emboli in vivo.  相似文献   

4.
OBJECTIVE: Molecular targeted MR imaging of human clots material in a model of pulmonary embolism using a fibrin-specific magnetic resonance imaging contrast agent (EP-2104R, EPIX Pharmaceuticals, Cambridge, MA). MATERIAL AND METHODS: Fresh ex vivo engineered thrombi (human blood) and human clots removed from patients were delivered in 11 swine. Molecular MR imaging with a 3D gradient-echo [3D fast field echo (3DFFE)] sequence and a navigator-gated and cardiac-triggered 3D inversion-recovery black-blood gradient-echo sequence (IR) was performed before thrombus delivery, after thrombus delivery but before contrast media application, and 2 hours after i.v. administration of 4 micromol/kg EP-2104R. MR images were analyzed by 2 investigators and contrast-to-noise ratio (CNR) was assessed. Thrombi were removed for assessment of gadolinium (Gd) concentration. RESULTS: Only after contrast media application were pulmonary emboli [freshly engineered thrombi (n = 23) and human clot material removed from patients (n = 25)] visualized as white foci on MR images. CNR was 13 +/- 3 (ex vivo engineered clot) and 22 +/- 9 (patient clot material) for the fast field echo (FFE)-sequence and 29 +/- 9 (ex vivo engineered clot) and 43 +/- 18 (patient clot material) for the IR-sequence, respectively. A high Gd concentration in the clots was found (82 +/- 43 microM for the freshly engineered and 247 +/- 44 microM for the clots removed from patients, respectively). CONCLUSIONS: EP-2104R allows for molecular MR imaging of human clot material in the pulmonary vessels of a swine model.  相似文献   

5.
PURPOSE: To reduce potential complications of fibrin deposition to catheter surfaces, there is increasing empiric use of alteplase as a catheter lock solution. The purpose is to evaluate the properties of alteplase when reconstituted in sterile water (SW) or bacteriostatic water (BW) for prolonged periods. MATERIALS AND METHODS: Alteplase in glass vials was reconstituted (1 mg/mL) with SW or BW (0.9% benzyl alcohol) in duplicates and stored at 37 degrees C. Biochemical assays were performed at days 0 and 7 and included optical clarity, protein concentration, percent protein monomer, and in vitro clot lysis activity. Microbiologic assays were performed on days 7 through 28 with use of a standardized antimicrobial effectiveness test (pass/fail) and pour-plate methods incubated at 22.5 degrees C (fungus, 3-7 days) or 32.5 degrees C (bacteria, 3-5 days). Organisms tested included Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus niger. RESULTS: Biochemical assay results were as follows: on day 0, all samples were clear/colorless; protein concentrations were 1.10 mg/mL +/- 0 in SW and 1.11 mg/mL +/- 0 in BW; percent protein monomer was 8.2% +/- 0.07 in SW and 98.6% +/- 0.07 in BW; and in vitro clot lysis activity (in percent of relative activity) was 100% in all samples. On day 7, all samples were clear/colorless, protein concentrations were 1.11 mg/mL +/- 0.07 in SW and 1.11 mg/mL +/- 0.07 in BW; percent protein monomer was 97.4% +/- 0.21 in SW and 96.1% +/- 0.21 in BW; and in vitro clot lysis activity (relative activity compared with day 0) was 91% +/- 2.8 in SW and 90% +/- 2.8 in BW. Microbiologic assays (US Pharmacopeia [USP] antimicrobial effectiveness test) yielded a failing result for alteplase reconstituted in SW and a passing result for alteplase reconstituted in BW. CONCLUSIONS: Alteplase reconstituted with SW or BW remains relatively stable with retained bioactivity when stored at 37 degrees C for as long as 7 days. Despite the biochemical similarities of the two solutions, only alteplase in BW met USP criteria as an effective antimicrobial solution. Further clinical evaluation is warranted.  相似文献   

6.
Imaging vascular thrombosis with 99mTc-labeled fibrin alpha-chain peptide.   总被引:7,自引:0,他引:7  
An agent that permits scintigraphic detection of chronic deep venous thrombosis (DVT) or pulmonary embolism (PE) would be a welcome addition to the armamentarium of nuclear medicine. Because fibrin is the integral part of each clot, old or fresh, we hypothesized that a 99mTc-labeled fibrin alpha-chain N-terminal peptide, Gly-Pro-Arg-Pro-Pro, that binds to the C-terminal portion of the gamma-chain of fibrin can detect DVT and PE. METHODS: The peptide was modified to Gly-Pro-Arg-Pro-Pro-Aba-Gly-Gly-(D)-Ala-Gly to permit efficient binding of 99mTc (99mTc-TP 850). The stability of the peptide was examined in vitro as well as in vivo. The ability of the agent to bind to rabbit, dog, and human fibrin and to inhibit adenosine diphosphate-induced platelet aggregation was examined. Blood clearance and 3-h tissue distribution were studied. DVT was induced in 8 rabbits using a stimulating electrode and in 2 rabbits by inserting a thrombin-soaked suture. PE was induced in 6 additional rabbits by introducing tantalum-impregnated blood clots into the right atrium, and the rabbits were radiographed to locate the emboli. 99mTc-TP 850 was then injected through a lateral ear vein, and each rabbit was imaged for up to 3 h. The rabbits were then killed, the heart and lungs were dissected and radiographed and the clots were harvested so that clot-to-blood radioactivity ratios could be determined. RESULTS: The peptide analog permitted efficient incorporation of 99mTc, which was stable in vitro and in vivo. The blood clearance was biphasic, with an alpha phase half-life of approximately 4 min (20%) and a beta phase half-life of approximately 13 min (88%). The mean binding of 99mTc-TP 850 to human, dog, and rabbit fibrin was 46% +/- 2%, 60% +/- 3%, and 56% +/- 2.5%, respectively, and the inhibitory concentration of 50% for dog and rabbit platelet aggregation was 236 pm and 167 pm, respectively. All clots, including 24-h-old pulmonary emboli, were delineated. The radioactivity associated with clots varied from 0.01 to 0.09 %ID/g, with clot-to-blood radioactivity ratios ranging from 1.2 to 12.0. However, 48-h-old pulmonary emboli had lysed and were seen neither by radiography nor by scintigraphy. CONCLUSION: A fibrin alpha-chain, N-terminal peptide that binds to the C-terminal portion of the gamma-chain of fibrin has been modified and labeled with 99mTc. The resultant peptide is stable in vitro and in vivo; binds to human, dog, and rabbit fibrin in large quantities; and inhibits platelet aggregation. The peptide clears rapidly from the blood and delineates experimental DVT and PE in rabbits. This agent is worthy of further investigation.  相似文献   

7.
In this study, the sensitivity of a novel fibrin-targeted contrast agent for fibrin detection was defined in vitro on human thrombus. The contrast agent was a lipid-encapsulated perfluorocarbon nanoparticle with numerous Gd-DTPA complexes incorporated into the outer surface. After binding to fibrin clots, scanning electron microscopy of treated clots revealed dense accumulation of nanoparticles on the clot surfaces. Fibrin clots with sizes ranging from 0.5-7.0 mm were imaged at 4.7 T with or without treatment with the targeted contrast agent. Regardless of sizes, untreated clots were not detectable by T(1)-weighted MRI, while targeted contrast agent dramatically improved the detectability of all clots. Decreases in T(1) and T(2) relaxation times (20-40%) were measured relative to the surrounding media and the control clots. These results suggest the potential for sensitive and specific detection of microthrombi that form on the intimal surfaces of unstable atherosclerotic plaque.  相似文献   

8.
A pentapeptide, Gly-Pro-Arg-Pro-Pro, with high affinity for alpha-chain-fibrin was labeled with (99m)Tc ((99m)Tc-TP850) and evaluated in swine to image experimental venous thromboembolism (deep vein thrombosis [DVT]) and pulmonary embolism (PE). METHODS: Scatchard analysis was performed to determine fibrin affinity for TP850 and the number of binding sites (receptors) per milligram of fibrin. DVT was induced in the left jugular vein and PE was induced by introducing a preformed autologous blood clot into the right atrium using a 7-French introducer sheath inserted into the right jugular vein. (99m)Tc-TP850 was injected at 4, 24, 48, 72, 96, or 120 h later. Animals were imaged for up to 4 h after injection, heparinized, and sacrificed. Lungs were extirpated, radiographed, and imaged, and the PE was removed. Other tissues, including blood and normal lungs, were harvested and, concomitantly, (99m)Tc was counted for determination of target-to-tissue ratios and the percentage injected dose per gram of tissue. RESULTS: The affinity for human fibrin was 10(-9) mol/L and there were >10(15) receptors per milligram of fibrin. DVT and PE were visualized for up to 4 h after injection with high DVT/blood (7.9-22.6), DVT/muscle (31.1-89.4), PE/blood (1-155), and PE/lung (0.8-245) ratios. Thereafter, the PEs fragmented spontaneously below the spatial resolution of the gamma-camera and, despite the high associated radioactivity, could not be localized in vivo. The fragmented clots were detectable by scintigraphy on excised lungs and provided excellent concordance with radiograms. CONCLUSION: (99m)Tc-TP850 with its modest affinity (10(-9) mol/L), rapid blood clearance, and high DVT and PE uptake is a promising agent for imaging vascular thrombosis.  相似文献   

9.
BACKGROUND AND PURPOSE:Previous studies have successfully created blood clot analogs for in vitro endovascular device testing using animal blood of various species. Blood components vary greatly among species; therefore, creating clot analogs from human blood is likely a more accurate representation of thrombi formed in the human vasculature.MATERIALS AND METHODS:Following approval from the Mayo Clinic institutional review board, human whole-blood and platelet donations were obtained from the blood transfusion service. Twelve clot analogs were created by combining different ratios of red blood cells + buffy coat, plasma, and platelets. Thrombin and calcium chloride were added to stimulate coagulation. Clot composition was assessed using histologic and immunohistochemical staining. To assess the similarities of mechanical properties to patient clots, 3 types of clot analogs (soft, elastic, and stiff) were selected for in vitro thrombectomy testing.RESULTS:The range of histopathologic compositions produced is representative of clots removed during thrombectomy procedures. The red blood cell composition ranged from 8.9% to 91.4%, and fibrin composition ranged from 3.1% to 53.4%. Platelets (CD42b) and von Willebrand Factor ranged from 0.5% to 47.1% and 1.0% to 63.4%, respectively. The soft clots had the highest first-pass effect and successful revascularization rates followed by the elastic and stiff clots. Distal embolization events were observed when clot ingestion could not be achieved, requiring device pullback. The incidence rate of distal embolization was the highest for the stiff clots due to the weak clot/device integration.CONCLUSIONS:Red blood cell–rich, fibrin-rich, and platelet-rich clot analogs that mimic clots retrieved from patients with acute ischemic stroke were created in vitro. Differing retrieval outcomes were confirmed using in vitro thrombectomy testing in a subset of clots.

In the treatment of acute ischemic stroke (AIS), the achievement of complete revascularization from a single mechanical thrombectomy attempt, termed first-pass effect (FPE), is associated with significantly improved outcomes for patients.1,2 Removing the clot in a fragmented manner increases the potential of embolization to new territories, a major contributing factor to poor neurologic outcomes due to additional brain infarction.3-5 Despite the advancement in the second-generation mechanical thrombectomy devices, the rates of FPE remain low, as low as 29% in the recently reported Contact Aspiration vs Stent Retriever for Successful Revascularization (ASTER) trial.6Previous studies have demonstrated that a wide variety of occlusive clots can cause large-vessel occlusion,7-11 and clot composition has been shown to have a significant impact on the success of mechanical thrombectomy procedures.7,12,13 These findings suggest that to further advance the success rates of stroke intervention, we must turn our attention to clot composition and compare treatment strategies using in vitro thrombectomy models of the cerebral vasculature. Previous studies have successfully created blood clot analogs for in vitro testing using animal blood of various species, which have significantly advanced our understanding of clot biomechanics and imaging characteristics.13-19 However, blood components and blood groups vary among species;20 thus, creating clot analogs with human blood is likely a more accurate representation of thrombi formed in the human vasculature.The hypothesis of the study was that the diverse range of clots retrieved from patients with AIS can be accurately replicated using human blood by mimicking the process by which clots form in vivo. The rationale for this study is that because the success of mechanical thrombectomy procedures is influenced by the composition of the clot, creating human clot analogs that accurately represent the different phenotypes retrieved from patients and testing them in an in vitro thrombectomy system will allow us to compare the performance of different thrombectomy devices and techniques. We will be able to determine the optimum treatment approach for each clot phenotype, thereby optimizing the chances of achieving the desired first-pass TICI 3 outcome in the clinical setting.1 To assess the similarities of mechanical properties to patient clots, we selected 3 types of clot analogs (soft, elastic, and stiff) for in vitro thrombectomy testing.  相似文献   

10.
PURPOSE: To characterize the biochemical stability and bioactivity of reconstituted alteplase when diluted to a concentration of 0.01 mg/mL in normal saline solution and stored at ambient temperature for as long as 24 hours in commercial saline solution bags. MATERIALS AND METHODS: Two commercially available formulations of lyophilized alteplase (2-mg and 50-mg vials, respectively) were reconstituted with sterile water to a final concentration of 1 mg/mL. For each vial configuration, 5 mg of alteplase (5 mL) was added to a commercial 500-mL bag of normal saline solution to achieve a 0.01-mg/mL targeted concentration. Solutions were assayed for optical clarity, pH, protein concentration, and in-vitro clot lysis activity. Assays of the solutions were performed at time points of 0 (control), 4, 8, and 24 hours at ambient room temperature and compared to controls. RESULTS: On visual inspection, aliquots of the diluted protein solutions in clear glass vials remained clear/colorless after 24 hours. Bioactivity (clot lysis assay) over the course of 24 hours at ambient temperature remained essentially unchanged relative to control (2-mg vial: mean of 98.3%, range of 93.7%-103.3%; 50-mg vial: mean of 103.1%, range of 100.6%-108.3%). The mean protein recovery rates (relative to targeted concentration) over a 24-hour period were 43% (range, 39%-46%) and 42% (range, 40%-45%) for the 2-mg and 50-mg vial configurations, respectively. CONCLUSIONS: Alteplase diluted in normal saline solution at a concentration of 0.01 mg/mL is biochemically stable and active at ambient temperature for as long as 24 hours as assessed by in vitro clot lysis assays. Alteplase appears to have a bimodal solubility profile in normal saline solution and further studies are required to determine the activity and solubility of alteplase concentrations lower than 0.01 mg/mL.  相似文献   

11.
The aim of this work was to produce a MoAb able to react with clots but not with fibrinogen. Monoclonal antibodies directed towards DD dimers, against specific products of plasmic digestion of cross-linked fibrin, were obtained. One of these antibodies, F 60/43/8, showed a 1.79 x 10(9) l mol-1 binding constant in spite of the presence of fibrinogen at a 4000 times greater concentration than the cross-linked fibrin. In vitro studies with 125I-F(ab')2 of F 60/43/8 showed that 34-80% of the radioactivity can be found in human clots, in the presence of physiologic concentrations of fibrinogen, and that 96-h washing does not remove the labelled F(ab')2 from the clot. 131I-F(ab')2 was injected into rabbits in which a clot had formed in an artery (six rabbits) or in a vein (six rabbits) of the left ear. Scintigraphic images of the clot were always obtained. In conclusion, the results of this work suggest that F 60/43/8 may be used as a specific antibody for the radioimmunodetection of thrombi.  相似文献   

12.
PURPOSE: To assess the clinical and economic benefits of catheter-directed thrombolysis (CDT) alone versus CDT with rheolytic percutaneous mechanical thrombectomy (PMT) for lower-extremity deep vein thrombosis (DVT). MATERIALS AND METHODS: Consecutive patients with acute iliofemoral DVT treated with CDT with urokinase between 1997 and 2003 were identified. Demographic characteristics and clinical and economic outcomes were compared between patients treated with CDT alone versus CDT plus PMT. RESULTS: Twenty-six limbs in 23 patients received CDT with urokinase, whereas 19 limbs in 14 patients were treated with CDT plus PMT. Mean treatment duration for CDT was 56.5 +/- 27.4 hours, compared with 30.3 +/- 17.8 hours for CDT plus PMT (P = .001). Mean urokinase dose for CDT was 6.70 +/- 5.9 million U compared with 2.95 +/- 1.82 million U for CDT plus PMT (P = .011). Urokinase CDT achieved complete clot lysis in 80.7% of limbs (n = 21) compared with 84.2% of limbs (n = 16) treated with CDT plus PMT (P = .764). The incidences of major bleeding (CDT, 7.7%; CDT plus PMT, 5.3%; P = .749) and pulmonary embolism (CDT, 3.8%; CDT plus PMT, 5.3%; P = .818) were similar. The mean urokinase and PMT device cost for CDT alone was $10,127 compared with $5,128 for CDT plus PMT (P = .026). CONCLUSIONS: Percutaneous CDT with rheolytic PMT is as effective as CDT alone for acute iliofemoral DVT but requires significantly shorter treatment and lower lytic agent dose, resulting in lower costs. Randomized studies to confirm the benefits of pharmacomechanical thrombolysis in the treatment of DVT are warranted.  相似文献   

13.
The efficacy of intrathrombic deposition vs. parathrombic infusion of urokinase (UK) and tissue-type plasminogen activator (t-PA) was investigated in a canine model. Gianturco coils were placed by transcatheter techniques into the iliac veins of 12 dogs. Venography obtained 48 hours later showed formation of large thrombi. After heparinization, UK (24,000-48,000 IU/ml) or t-PA (12,500-25,000 IU/ml) was spray-injected at high pressure throughout test clots every half-hour using a steel catheter with multiple side holes. Between injections, the agent was infused below the clots. The contralateral thrombi received an equivalent dose of fibrinolytic agent by continuous infusion. In six cases, plasminogen was injected into test clots prior to activator treatment. Thrombi spray-injected with either activator lysed in 64 +/- 26 minutes. Four of six thrombi treated with parathrombic urokinase infusion showed partial lysis after 133 +/- 50 minutes. After parathrombic infusion of t-PA, three clots showed complete lysis, one showed partial lysis, and two demonstrated no lysis. There was no significant difference in lysis rate between intrathrombic UK and t-PA nor did prior intrathrombic injection of plasminogen accelerate lysis. In summary, intrathrombic injection of highly concentrated UK or t-PA lysed subacute thrombi more effectively than parathrombic infusion.  相似文献   

14.
Rheolytic catheter for percutaneous removal of thrombus.   总被引:10,自引:0,他引:10  
The authors present a percutaneous thrombectomy system (rheolytic thrombectomy catheter [RTC]) in which high-velocity jets of saline solution are used to lyse and remove thrombus. The catheters (4-6 F) direct a 10,000-15,000-psi (0.7-1.05 x 10(5)-kPa) jet of saline solution onto an exhaust port from orifices at the end of the catheter. The jet entrains clot and resulting fragments and brings them into the high-velocity region for lysis and removal. Whole blood clots (10-15 cm) placed in 6-9-mm-diameter tubing were completely dissolved and removed with the RTC in less than 1 minute. In vivo use in a canine model resulted in lysis and removal of clots from a femoral artery, without vessel damage. The small caliber, flexibility, and effective lysis of this system suggest its potential usefulness in large central vessels that are difficult to access surgically and in small-diameter vessels that require more rapid removal of thrombus than can be achieved with thrombolytic therapy.  相似文献   

15.
PURPOSE: Low-power ultrasonic (US) energy is capable of clot dissolution in vivo. The combination of US energy plus alteplase may further accelerate clot lysis; however, the effects of cavitation could potentially denature and inactivate the lytic protein. The purpose of this study was to determine the bioactivity and stability of alteplase when exposed to US energy with use of a novel intravascular US wire in an in vitro model. MATERIALS AND METHODS: The model consisted of a 6.4-mm-diameter silicone tube closed at one end and filled with alteplase (1 mg/mL) in a water bath (37 degrees C). A 95-cm US wire (0.025-inch diameter, 20 kHz) was inserted into the tube and connected to a variable power generator. The wire delivers low-power acoustic energy 360 degrees around its 20-cm active length and was irrigated by a continuous infusion of purified water. Fresh 6-mL alteplase aliquots were exposed to US energy and tested in duplicates. Zero (control), 1 W, or 2 W of energy was delivered to individual test samples for zero (control), 0.5, 3, or 6 minutes. Alteplase samples were assayed for optical clarity and protein concentration with use of UV spectrophotometry, for percent protein monomer with use of high-performance size-exclusion chromatography, and for in vitro clot lysis activity. RESULTS: In the control samples, optical clarity was clear or colorless in all samples; protein concentration was 1.02 mg/mL +/- 0; protein monomer was 98%; and clot lysis activity was 108% per mg +/- 1. In the test samples, optical clarity was clear or colorless in all samples; protein concentrations at 0.5, 3, and 6 minutes were 0.98 mg/mL +/- 0.02, 0.93 mg/mL +/- 0.01, and 0.86 mg/mL +/- 0.02, respectively, at 1 W, and 1.00 mg/mL +/- 0.03, 0.94 mg/mL +/- 0.10, and 0.84 mg/mL +/- 0.17, respectively, at 2 W. Protein monomer was 98% for all samples. Clot lysis activity levels at 0.5, 3, and 6 minutes were 111% per mg +/- 1, 110% per mg +/- 1, and 115% per mg +/- 1, respectively, at 1 W, and 110% per mg +/- 0, 111% per mg +/- 1, and 116% per mg +/- 2, respectively, at 2 W. CONCLUSIONS: Alteplase solutions exposed to low-power US energy for as long as 6 minutes remained fully active and stable as determined by protein assays. Further investigation is warranted with use of combinations of US energy and alteplase.  相似文献   

16.
Spin echo MR imaging has not permitted reliable differentiation between intraluminal blood clot and tumor thrombus. This study assessed the role of ECG referenced repetitive gradient refocused echo (cine GRE) imaging for the differentiation of intravascular tumor from blood clot. Cine GRE images were reviewed in 23 patients, 11 of whom had intravascular tumor and 12 of whom had intravascular blood clots. Percentage contrast between the lesion and skeletal muscle as the reference tissue was determined from a subjective review of the images and objective signal intensity measurements. Intravascular clots were found to be lower in signal intensity than muscle (mean -55 +/- 29%). Intravascular tumors showed higher signal intensity relative to muscle (mean +17 +/- 9%) with the exception of myxomas (n = 2), which had signal intensity values relative to muscle as low as clots (mean -41 +/- 17%). Three masses in the inferior vena cava were composed of central tumor and peripheral clot; the two components could be differentiated with cine GRE imaging. Cine GRE imaging provides adequate signal intensity differences to visualize intravascular masses and helps to differentiate intravascular clot from tumor thrombus. However, if the tumor contains substantial amounts of iron, then the signal is also low and consequently clot and thrombus may not be distinguishable. This can occur in some atrial myxomas.  相似文献   

17.
In vitro evaluation of a retrievable low-profile nitinol vena cava filter   总被引:1,自引:0,他引:1  
PURPOSE: To evaluate the clot-trapping ability, stability, and migration of a new low-profile, retrievable inferior vena cava (IVC) filter in an in-vitro model. MATERIALS AND METHODS: The SafeFlo IVC filter consists of two superelastic nitinol wires that form a double-ring platform and spiral filter. The filter is collapsed into a 5-6-F catheter and delivered into the IVC model. The in-vitro model closely simulates the physical parameters of flow in the human IVC. Human blood clots of 2-mm and 4-mm diameters and 3-cm lengths were injected into the flow system in sets of five clots. Filter delivery and retrieval were performed in every series. Filtration was evaluated in IVC models of 20-mm and 24-mm lumen diameter in vertical and horizontal positions. Stability and migration of the filter were evaluated by direct vision of maintenance of position and shape before and after clot trapping. RESULTS: Filter delivery and retrieval were straightforward and repeatable in a total of 20 procedures. The filters maintained shape and position throughout the study. A total of 248 clots were injected and 225 (90.7%) were trapped. The individual tests in horizontal and vertical positions with either clot size demonstrated trapping rates of 85.7%-97.1%. CONCLUSIONS: The SafeFlo IVC filter is a stable and effective filter in an in-vitro model. The filter design is amenable to simple delivery and retrieval.  相似文献   

18.
Purpose: To investigate the influence of hyperthermia up to 45°C on fibrinolysis with recombinant tissue-type plasminogen activator (rt-PA). Methods: Standardized fibrin clots were incubated in a water bath for 5 hr with either rt-PA (test group) or 0.9% sodium chloride (control group) and blood plasma at temperatures of 30–45°C. Concentrations of D-dimer and time to complete clot lysis were measured. Results: The activity of fibrinolysis with rt-PA rose with increasing temperature: time to lysis approximately halved from 30°C to 40°C and the concentration of D-dimer tripled. In the control group clot size did not change. Conclusions: Activity of rt-PA-induced fibrinolysis rises distinctly with higher temperatures. Since even healthy subjects show a physiologic decline in body temperature in the extremities, in patients with occlusive arterial disease decreased activity of fibrinolysis with rt-PA can be expected. Controlled hyperthermia may improve fibrinolysis with rt-PA and should be investigated in vivo.  相似文献   

19.
Pilger  E; Lammer  J; Bertuch  H; Steiner  H 《Radiology》1986,161(3):597-599
In order to investigate and compare the fibrinolytic activity of streptokinase, streptokinase-Glutamine-plasminogen, and urokinase for intraarterial fibrinolysis, as in vitro test and a prospective trial were performed. For the in vitro demonstration of lytic activity, fibrin plates with plasminogen and fibrin plates without plasminogen were incubated with streptokinase; with streptokinase-plasminogen in molar proportions of 1:1, 1:2, and 2:1, and with urokinase. In order to examine the in vivo activity of the different lytic solutions, 98 patients suffering from peripheral arterial occlusions were divided into three homogeneous groups for treatment with streptokinase, streptokinase-plasminogen, and urokinase. Although urokinase was superior to streptokinase on the fibrin plate with plasminogen, no difference was demonstrated in vivo between the two lytic agents. Streptokinase-plasminogen in a molar proportion of 1:2 showed significantly higher fibrinolytic activity than any other solution. Therefore, the fibrinolytic agent of choice for intrathrombotic injections seems to be a 1:2 solution of streptokinase with plasminogen or with the lytic enzyme plasmin itself.  相似文献   

20.
BACKGROUND: The intraarterial administration of thrombolytic agents is associated with clinical benefits in patients with acute peripheral arterial occlusion, and urokinase has been the agent that has become the standard of care in the United States. Recombinant prourokinase (r-ProUK) offers potential as a novel agent with improved fibrin specificity and, as such, may offer advantages as an attractive alternative to urokinase. METHODS: A randomized, double-blind, parallel, phase II, prospective multicenter trial was undertaken to compare three doses of intra-arterial, catheter-directed r-ProUK (2 mg, 4 mg, or 8 mg/hr for 8 hrs, then 0.5 mg/hr) versus one dose of tissue-culture urokinase (4,000 IU/min for 4 hrs, then 2,000 IU/min) for the treatment of acute lower extremity arterial occlusion of 14 days' duration or less (n = 241). The primary endpoint was complete (>95%) lysis of the occluding thrombus after 8 hours of infusion. RESULTS: Increased clot lysis at 8 hours, decreased fibrinogen concentration, and an increased rate of hemorrhagic events were observed as the r-ProUK dose was increased from 2 mg/hr to 8 mg/hr. Similarly, a decreased duration of study drug infusion was seen, decreasing from 16.7 +/- 0.90 hours in the 2 mg/hr group to 12.7 +/- 0.97 hours in the 8 mg/hr group. The results for the urokinase group decreased to a level between those observed for the 2 mg and 8 mg r-ProUK group with respect to clot lysis at 8 hours, fibrinogen decrement, and bleeding complications, approximating those observed in the 4 mg/hr r-ProUK group. These results were achieved with a relatively low rate of major bleeding events and no episodes of intracranial hemorrhage. CONCLUSIONS: The 8 mg/hr dose of r-ProUK was associated with an increased rate of thrombolysis relative to the other treatment groups, associated with a slightly increased frequency of bleeding complications and decrements in fibrinogen concentration. Conversely, the 2 mg/hr r-ProUK dose was associated with a slightly slower rate of thrombolysis, but bleeding complications and fibrinogenolysis were diminished. r-ProUK is a novel thrombolytic agent with a dose-related safety and efficacy profile. As such, it offers potential as a useful tool in the treatment of peripheral vascular occlusion.  相似文献   

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