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1.
Free-flap failure is in the order of 4 to 10 percent. Heparin is more effective at preventing venous thrombosis than arterial thrombosis. This study was undertaken to investigate the efficacy of delivering heparin at a high dose locally but low dose systemically (heparin infusion via a catheter placed proximal to the venous anastomosis) to prevent venous thrombosis in microsurgery. A model of venous thrombosis was first established by a venous inversion graft in the rat femoral vein (this was performed in seven animals and resulted in 100 percent thrombosis). Saline and heparin were delivered proximal to the inverted vein graft to assess the effect of each in preventing venous thrombosis. Flow/patency distal to the inverted vein graft was assessed by observation under the microscope, the milk test, and rate of flow (flowmeter). Saline infused via a catheter proximal to the venous inversion graft resulted in 100 percent thrombosis in 10 animals. Heparin (100 U/ml at 2 to 3 ml/hour) infused through a catheter for 2 hours proximal to the anastomosis resulted in flow in all 10 animals during the infusion. Blood was also taken before beginning the procedure (control) and after the heparin infusion distal to the anastomosis (local partial thromboplastin time) as well as in the contralateral femoral vein (systemic). The control for all animals that received heparin was <3 minutes. The systemic partial thromboplastin time after heparin infusion was <3 minutes in seven animals, 3.3 minutes in two animals, and >7 minutes in one animal. The local partial thromboplastin time distal to the inverted vein graft was >10 minutes in nine animals and 3.7 minutes in one animal. The study also had a clinical component, in which a catheter was placed in a vein of the free flap, and heparin was infused over 5 days. This technique has been used in 83 consecutive free flaps. In three recent free flaps performed on the limbs, the local partial thromboplastin time (close to the anastomosis) was raised but the systemic time was normal. This technique offers a method in preventing venous thrombosis in microsurgery. It is simple to implement and is not associated with the systemic complications of heparin.  相似文献   

2.
Thrombosis is the end result of two closely interrelated processes: the coagulation cascade and the platelet aggregation process. To determine their relative contribution, we used pharmacologic agents that selectively block each process. The specific effect of each pharmacologic agent on either fibrin deposition or platelet activity was confirmed morphologically by scanning electron microscopy and was substantiated with ADP-induced platelet aggregation and blood clotting time determinations. Forty-two rats had both femoral arteries subjected to a standardized crush-avulsion injury. A total of 84 femoral microvascular anastomoses were subsequently performed. None of the 24 control anastomoses treated with saline remained patent, whereas 6 of 24 of the anastomoses treated with dazmagrel (a selective thromboxane synthetase and platelet aggregation inhibitor), 2.5 mg/kg IV, remained patent and 18 of 24 of those treated with a single dose of heparin, 200 U/kg IV, remained patent. All 12 anastomoses treated with both drugs remained patent but developed a 33 percent hematoma rate. We conclude that in this microvascular model, fibrin mesh deposition is a more significant factor than platelet aggregation in the pathogenesis of occlusional thrombosis within traumatized arteries. Its temporary inhibition with a single dose of heparin yielded a 75 percent improvement in patency rate.  相似文献   

3.
Despite major improvements in tools and significant refinements of techniques, microsurgical anastomosis still carries a significant risk of failure due to microvascular thrombosis. The key to improving the success of microvascular surgery may lie in the pharmacologic control of thrombus formation. Central to pathologic arterial thrombosis are platelets. Glycoprotein IIb/IIIa is a highly abundant platelet surface receptor that plays a major role in platelet aggregation by binding platelets to each other through the coagulation factor fibrinogen. To explore the ability of antithrombotic agents to prevent microvascular thrombosis, a rabbit ear artery model was used in which a standardized arterial injury results in predictable thrombus formation. This model was used to examine whether SR121566A, a specific and potent glycoprotein IIb/IIIa inhibitor, can successfully prevent microsurgical thrombosis.Using a coded, double-blind experimental design, 20 rabbits (40 arteries) were assigned to four treatment groups: (1) saline injection (n = 10), (2) acetylsalicylic acid 10 mg/kg (n = 10), (3) heparin 0.5 mg/kg bolus with subsequent intermittent boluses of 0.25 mg/kg every 30 minutes (n = 10), and (4) SR121566A 2 mg/kg bolus (n = 10). After vessel damage and clamp release, arteries were assessed for patency at 5, 30, and 120 minutes by the Acland refill test. Coagulation assays, in vivo bleeding times, and ex vivo platelet aggregation studies were also conducted. Scanning electron microscopy was used to examine mural thrombus composition.A significant, fourfold increase in vessel patency following administration of SR121566A over saline control (80 percent versus 20 percent patency, respectively, at 35 minutes after reperfusion, p < 0.01) was noted. This was correlated with marked inhibition of ex vivo platelet aggregation. This antiplatelet treatment did not prolong coagulation assays (mean international normalized ratio: saline, 0.66 +/- 0.04; SR121566A, 0.64 +/- 0.03; mean thromboplastin time: saline, 19.63 +/- 0.67; SR121566A, 17.87 +/- 3.27) and bleeding times (mean bleeding time: saline, 42 +/- 4; SR121566A, 48 +/- 6). Scanning electron microscopy demonstrated extensive platelet and fibrin deposition in control vessel thrombi. In contrast, thrombi from SR121566A-treated vessels demonstrated predominance of fibrin with few platelets when examined under scanning electron microscopy.Administration of SR121566A was associated with a significant increase in vessel patency, without deleterious effects on coagulation assays or bleeding times. The increase in vessel patency was correlated with inhibition of platelet aggregation and decreased platelet deposition, as demonstrated by scanning electron microscopy. Glycoprotein IIb/IIIa antagonists represent a new class of anti-platelet agents that may be suited for inhibiting microsurgical thrombosis. This study supports further investigation into the use of these agents in microsurgery.  相似文献   

4.
In a blind, randomized study, two groups, each of seven rabbits, were treated with either a very low dose of human melanoma cell line-derived tissue-type plasminogen activator (t-PA) or isotonic saline. t-PA (0.067 mg/kg of body weight) was administered intraaortically, 20 percent being given as a 30-second "bolus" infusion just prior to the reperfusion of intimectomized central ear arteries and the rest as a continuous infusion during the next 2 hours. Arteriotomic bleeding times, accumulations of 32P-labeled platelets, patency, and sizes of thrombus deposits 2 hours after reperfusion were recorded. To confirm the presence of tissue plasminogen activator in plasma, fibrin-plate lysis assays of arterial plasma were performed immediately before and 1/2 hour and 2 hours after starting drug infusion. Arteriotomic bleeding times were similar in both groups. Transient "oozing" from wound edges occurred in 40 percent of rabbits treated with tissue plasminogen activator. Patency was significantly increased and thrombus deposits were smaller in the tissue plasminogen activator group. Plasma from animals treated with tissue plasminogen activator caused massive lysis of fibrin plates, whereas plasma from control animals caused little or no lysis. Platelet accumulations were very similar in both groups, indicating that occlusive thrombi mainly consisted of other elements than platelets (e.g., fibrin and red cells). Scanning electron microscopy showed normally adhering and aggregating platelets in both groups. This study shows that mild fibrinolytic stimulation with tissue plasminogen activator significantly improves patency in severely traumatized small-caliber arteries and indicates that such treatment may be one approach to prevent thrombosis at microvascular anastomotic sites.  相似文献   

5.
A new model of microvascular thrombosis is presented, with the evaluation of single-dose heparin in the prevention of microvascular thrombosis. The technique, which involves arterial crushing and an arteriotomy with intimal abrasion, was performed on the superficial femoral artery of the rat. The model was applied to a series of 30 consecutive rat superficial femoral arteries. A 100 percent thrombosis rate was seen immediately and at 24 hours in 10 nonheparinized animals. An operator control group of 10 vessels without intimal abrasion had a patency rate of 100 percent immediately and at 24 hours. Ten vessels following single-dose heparin and intimal abrasion were all patent initially, with 7 remaining patent at 24 hours. Reproducibility of the model was documented by a second operator with similar results. Utilizing this model, single-dose heparin was effective in maintaining vessel patency.  相似文献   

6.

Background

Hemodialysis arteriovenous synthetic grafts (AVG) provide high volumetric blood flow rates shortly after surgical placement. However, stenosis often develops at the vein-graft anastomosis contributing to thrombosis and early graft failure. Two novel fusion proteins, ANV-6L15 and TAP-ANV, inhibit the tissue factor/factor VIIa coagulation complex and the factor Xa/factor Va complex, respectively. Each inhibitor domain is fused to an annexin V domain that targets the inhibitor activity to sites of vascular injury to locally inhibit thrombosis. This study’s objective was to determine if these antithrombotic proteins are safe and effective in inhibiting AVG stenosis.

Methods

A bolus of either TAP-ANV or ANV-6L15 fusion protein was administered intravenously immediately prior to surgical placement of a synthetic graft between the external jugular vein and common carotid artery in a porcine model. At surgery, the vein and artery were irrigated with the anti-thrombotic fusion protein. Control animals received intravenous heparin. At 4 weeks, MRI was performed to evaluate graft patency, the pigs were then euthanized and grafts and attached vessels were explanted for histomorphometric assessment of neointimal hyperplasia at the vein-graft anastomosis. Blood was collected at surgery, immediately after surgery and at euthanasia for serum metabolic panels and coagulation chemistries.

Results

No acute thrombosis occurred in the control group or in either experimental group. No abnormal serum chemistries, activated clotting times or PT, PTT values were observed after treatment in experimental or control animals. However, at the vein-graft anastomosis, there was no difference between the control and experimental groups in cross-sectional lumen areas, as measured on MRI, and no difference in hyperplasia areas as determined by histomorphometry. These results suggest that local irrigation of TAP-ANV or ANV-6L15 intra-operatively was as effective in inhibiting acute graft thrombosis as intravenous administration of heparin, but failed to inhibit hyperplasia development and stenosis in AVG.  相似文献   

7.
The high rate of thrombosis of 1.0-mm polytetrafluoroethylene (PTFE) grafts has limited their use in microvascular surgery. One possible reason for this is the blood-gas interface due to entrapped air in the interstices. The present study examines the effect on patency rates of elimination of this blood-gas interface by high pressurization. Comparing pressurized and nonpressurized grafts in the same animals showed a patency rate of 100 percent at 7 days for treated grafts, while the control (nonpressurized) grafts had all clotted by 1 hour. The implications for microvascular surgery as well as vascular surgery in general are discussed.  相似文献   

8.
We evaluated in a rat model the effects of a homologous fibrin glue in reversing the effects of Adriamycin on adherence and take of skin grafts. A total of 40 male Fisher rats were used in the study. During the first phase of the experiment, the animals were assigned to either group I (N = 10) receiving normal saline or group II (N = 10) receiving 6 mg/kg Adriamycin by tail vein injection 24 hours before surgery. Skin grafts with and without fibrin glue were placed over wounds in the backs of the animals and adherence was measured at 24 and 48 hours. In the second phase (N = 20), the experiment was repeated, this time evaluating the total area of skin graft take at 7 days. Fibrin glue was found to increase adherence and take of skin grafts in all Adriamycin-treated animals.  相似文献   

9.
The effect of fibrin glue on skin grafts in infected sites.   总被引:1,自引:0,他引:1  
Fibrin bonding of skin grafts to wounds is an essential part of the graft-adherence process. Bacteria, in concentrations greater than 10(5)/gm of tissue, are associated with graft failure. Sixty-five rats were randomly divided into three groups, dorsal split-thickness skin grafts were harvested, and the sites were inoculated with Staphylococcus aureus. After incubation, each wound was quantitatively biopsied and treated with saline, fibrin glue with aprotinin, or fibrin glue alone. We found that the addition of commercially available fibrin glue with or without the antifibrinolytic agent aprotinin is capable of restoring graft adherence to normal levels in graft sites infected with greater than 10(5) bacteria/gm of tissue. Fibrin glue may have potential for increasing skin-graft take in the clinical situation where the graft bed is infected.  相似文献   

10.
Coronary artery bypass graft surgery (CABG) is routinely used to restore blood flow to diseased cardiac muscle due to coronary artery disease. The patency of conventional grafts decreases with time, which is due to thrombosis and formation of neointima. A primary cause of graft failure is the mechanical damage inflicted to the graft during harvesting, including removal of surrounding tissue accompanied by high pressure saline distension to overcome vasospasm (both causing considerable mechanical trauma). The aim of this study was to compare the ultrastructural features of human saphenous vein (SV) grafts harvested conventionally and grafts prepared using an atraumatic 'no-touch' harvesting technique introduced by Souza (1996). The results of this study showed a better preservation of the lumenal endothelium and medial vascular smooth muscle (SM) in 'no-touch' versus conventional grafts. A 'fast' (within 30 min) response of SM cells to conventional harvesting was noted where features of both SM cell division and apoptosis were observed. It is concluded that the 'preserved' nature of the 'no-touch' aortocoronary SV grafts renders them less susceptible to thrombotic and atherosclerotic factors than grafts harvested conventionally. These features are suggested to contribute to the improved early patency rate described using the no-touch technique of SV harvesting.  相似文献   

11.
The rationale for the design of surgical models of microvascular thrombosis is discussed, and a new model, the arterial inversion graft (AIG), is described and evaluated in the New Zealand white rabbit. Femoral artery segments of predetermined length are excised, gently turned inside-out, and resutured into their native position. Blood flow is restored, and at varying time intervals, vessel patency is assessed through the direct "milking test." In this study, three groups of 20 arterial inversion grafts of 2, 5, and 10 mm in length are created and evaluated for patency at 1 hour and again at 7 days. The incidence of femoral artery occlusion in this model appears to be an increasing function of arterial inversion graft length both at 1 hour--30 percent (2 mm), 80 percent (5 mm), and 100 percent (10 mm)--and at 7 days--65 percent (2 mm), 90 percent (5 mm), and 100 percent (10 mm). This proportionality suggests the arterial inversion graft may be adjusted in length to provide an incidence of vessel occlusion best suited to the needs of any particular experiment.  相似文献   

12.
Fibrin is shown to be the agent responsible for the adherence of biological dressings and of autografts to wounds. Its presence is associated with graft success, and its absence with graft failure. The results suggest that the deposition of fibrin provides the basis for the anti-bacterial actions of biological dressings and for the sterilization of the wound under adherent autografts. The total number of bacteria per gram of tissue in the wound, though important, is not critical to the result of skin grafting. The mechanism by which different organisms cause grafts to fail is by the production of plasmin and proteolytic enzymes which dissolve the important fibrin scaffold--thus ensuring their own survival. Thus, it is the levels of these (and the numbers of organisms efficient in producing them) which cause success or failure of applied skin grafts.  相似文献   

13.
Unfractionated heparin is often used to prevent thrombosis in microvascular surgery, but a major drawback of heparin therapy is increased bleeding. Low-molecular-weight heparins prevent venous thrombosis as effectively as heparin and have better bioavailability and a longer plasma half-life, which explains the increased use of low-molecular-weight heparins as substitutes for heparin in clinical practice. However, the ability of low-molecular-weight heparins to prevent arterial thrombosis has been debated. In this study, the authors compared the antithrombotic and antihemostatic effects of heparin and the low-molecular-weight heparin dalteparin in a rat model of arterial thrombosis. A segment of the left common carotid artery was isolated between vascular clamps and opened longitudinally. An endarterectomy was performed and the arteriotomy was closed with a running suture. The antithrombotic effect (vascular patency 31 minutes after reperfusion) and the surgical bleeding were measured. Groups of 10 rats were treated in a blind, random fashion with intravenous injection of one of the following substances 1 minute before clamp release. Three groups received a bolus of heparin (20, 60, or 180 IU anti-factor Xa/kg), three groups received dalteparin (60, 180, or 540 IU anti-factor Xa/kg), and one group was treated with vehicle (saline). Heparin 180 IU/kg produced a distinct antithrombotic effect compared with the control group (p = 0.03), but it also significantly increased the surgical bleeding to 2.0 g compared with 1.5 g in the control group (medians, p = 0.01). Dalteparin 180 and 540 IU/kg also produced a powerful antithrombotic effect (p = 0.01 and p = 0.03, respectively). In contrast to heparin, 180 IU/kg dalteparin did not increase the surgical bleeding (median, 1.5 g; p = 0.37 versus controls). Dalteparin 540 IU/kg increased the median surgical bleeding to 2.6 g (p = 0.06 versus controls). The nonsignificant difference may be explained by the great interindividual variation of surgical bleeding in the high-dose dalteparin group. Dalteparin prevented arterial thrombosis as effectively as unfractionated heparin. In contrast to heparin, dalteparin did not increase the surgical bleeding, which indicates that dalteparin instead of heparin can be used to prevent thrombosis in microvascular surgery.  相似文献   

14.
Arii K  Igarashi H  Arii T  Katayama Y 《Life sciences》2002,71(25):2983-2994
The therapeutic efficacy of ozagrel sodium (ozagrel), alone and in combination with heparin, and its therapeutic time window were studied in a photochemically induced thrombotic cerebral infarction rat model. Cerebral artery thrombosis was induced by irradiating the brain with green light through intact skull using rose bengal as the photosensitizing dye. One set of animals was treated immediately after thrombosis with (1) vehicle, (2) 10 mg/kg ozagrel in saline, intravenously (i.v.), (3) 150 U/kg unfractioned heparin, subcutaneously (s.c.), or (4) ozagrel, i.v. plus heparin, s.c. Infarct volume was significantly smaller and edema was reduced in the ozagrel-treated groups compared to the vehicle-treated group; heparin did not convey additional benefit. In another set of animals, rats were given either vehicle or 10 mg/kg ozagrel in saline, i.v., 60 min or 120 min after induction of thrombosis. Ozagrel reduced infarct volume, but its effect diminished with delayed administration. The therapeutic window was determined to be less than 60 minutes after induction of thrombosis.  相似文献   

15.
In this study, 100 rabbits were used to assess the efficacy of five different methods of microvascular anastomosis where a vessel diameter discrepancy of 5:1 existed. The inferior vena cava of the rabbit was used as a graft in the femoral artery. In 50 percent of the rabbits the graft was reversed to assess the effects on flow. When explored between 7 and 10 days after anastomosis, an overall patency rate of 96 percent was recorded. Three grafts were not patent in the reversed group and one was not patent in the nonreversed group. There was no significant statistical difference in patency rates between any of the groups, as calculated by the Fisher's exact probability test. The tapered end-to-end and side-to-end anastomoses were found to be the most rapid and simplest methods to perform.  相似文献   

16.
The utility for a prosthetic microvascular graft is well demonstrated, but previous studies have been inconclusive. Expanded polytetrafluoroethylene (Gore-Tex) has been most widely tested as a prosthetic graft. Polytetrafluoroethylene is composed of transverse nodules connected by long fibrils. This study evaluates the effect of fibril length on observed patency in a 1-mm inner-diameter system. Fibril lengths tested were 30, 60, 90, and 120 micron. One-hundred and sixty-three grafts were implanted in the abdominal aorta of Sprague-Dawley rats by a single surgeon using a standardized technique. No anticoagulants were used. Grafts were harvested at predetermined times and evaluated macroscopically, by scanning electron microscope, and by standard histology. The highest patency observed was 97.7 percent in the 90-micron fibril-length grafts. Fibril morphology also affected patency. Increased patency was associated with an amorphous fibril pattern. The graft functioned as a matrix for the formation of a pseudoartery, complete with monocell-thick intima and smooth-muscle media. A foreign-body reaction was observed in the 60-micron fibril-length graft only. Expanded polytetrafluoroethylene does show promise as a microvascular graft. Both fibril length and morphology affect observed patency.  相似文献   

17.
生物血管异种移植的初步研究   总被引:2,自引:1,他引:1  
目的为了寻求一种新的小口径血管代用品,建立异种移植的动物实验模型,以观察异种移植物的安全性、可靠性、通畅性及组织学改变。方法共采用17只杂种雌性犬,实验组10只,植入经环氧化物处理的猪血管移植物;对照组7只,植入人造血管。手术方法为右侧股动静脉瘘。术后通过超声和血管造影方法来观察移植血管的通畅性,并在术后3月将移植物取出,进行病理学检查,观察移植前后移植物的组织学改变。结果术后第一周、二周行Doppler超声检查结果,两组动静脉瘘均通畅,2周内血管通畅率为100%。术后3个月动脉造影检查后,生物血管组(PG)通畅5只,通畅率62.5%,e-PTFE组通畅4只,通畅率66.7%。两组数据统计学处理,差异无显著性(P>0.05)。术后3月对移植物取材,进行光镜及扫描电镜病理学检查,通畅的生物血管吻合口无狭窄,吻合部位有新的内膜覆盖,周围组织无钙化,有新生的内皮细胞覆盖。结论经环氧化物处理的猪的血管移植物(PG)生物血管作为异种移植物,生物相容性好,具有一定的可行性。  相似文献   

18.
The present study was performed to compare vascularized and nonvascularized onlay bone grafts to investigate the potential effect of graft-to-recipient bed orientation on long-term bone remodeling and changes in thickness and microarchitectural patterns of remodeling within the bone grafts. In two groups of 10 rabbits each, bone grafts were raised bilaterally from the supraorbital processes and placed subperiosteally on the zygomatic arch. The bone grafts were oriented parallel to the zygomatic arch on one side and perpendicular to the arch on the contralateral side. In the first group, vascularized bone grafts were transferred based on the auricularis anterior muscle, and in the second group nonvascularized bone grafts were transferred. Fluorochrome markers were injected during the last 3 months of animal survival, and animals were killed either 6 or 12 months postoperatively. The nonvascularized augmented zygoma showed no significant change in thickness 6 months after bone graft placement and a significant decrease in thickness 1 year after graft placement (p < 0.01). The vascularized augmented zygoma showed a slight but statistically significant decrease in thickness 6 months after graft placement (p < 0.003), with no significant difference relative to its initial thickness 1 year after graft placement. In animals killed 6 months after bone graft placement, both the rate of remodeling and the bone deposition rate measured during the last 3 months of survival were significantly higher in the vascularized bone grafts compared with their nonvascularized counterparts (p < 0.02). By 1 year postoperatively, there were no significant differences in thickness, mineral apposition rate, or osteon density between bone grafts oriented perpendicular and parallel to the zygomatic arch. These findings indicate that the vascularity of a bone graft has a significant effect on long-term thickness and histomorphometric parameters of bone remodeling, whereas the direction of placement of a subperiosteal graft relative to the recipient bed has minimal effect on these parameters. In vascularized bone grafts, both bone remodeling and deposition are accelerated during the initial period following graft placement. Continued bone deposition renders vascularized grafts better suited for the long-term maintenance of thickness and contour relative to nonvascularized grafts.  相似文献   

19.
Changes in length, external diameter, wall thickness, and morphology were examined in 60 intraarterial vein grafts and 30 intravenous vein grafts inserted in rabbit femoral vessels. Half of each graft type was explored at 6 or 12 months, giving four experimental groups. The overall patency for intraarterial grafts at exploration was 98 percent and for intravenous grafts 100 percent. In comparison with the initial graft length resected, all four groups were significantly shorter at the completion of anastomosis, and three of the four groups also were significantly shorter at exploration. The overall loss in length of grafts varied between 26 and 30 percent of original length. External diameter was significantly increased (from between 133 and 201 percent) in all four groups at exploration compared to the normal femoral vein. Intravenous grafts maintained normal vein morphology to 12 months. Intraarterial grafts were modified by the ingrowth of smooth-muscle cells from the recipient artery, thereby creating a neointima that significantly thickened their walls at both 6 and 12 months.  相似文献   

20.
Vascular surgeries such as coronary artery bypass require small diameter vascular grafts with properties that are not available at this time. Approaches using synthetic biomaterials have been not completely successful in producing non-thrombogenic grafts with inner diameters less than 6 mm, and there is a need for new biomaterials and graft designs. We propose silk fibroin as a microvascular graft material and describe tubular silk scaffolds that demonstrate improved properties over existing vascular graft materials. Silk tubes produced using an aqueous gel spinning technique were first assessed in vitro in terms of thrombogenicity (thrombin and fibrinogen adsorption, platelet adhesion) and vascular cell responses (endothelial and smooth muscle cell attachment and proliferation) in comparison with polytetrafluoroethylene (PTFE), a synthetic material most frequently used for vascular grafts. Silk tubes were then implanted into the abdominal aortas of Sprague-Dawley rats. At time points of 2 weeks and 4 weeks post implantation, tissue outcomes were assessed through gross observation (acute thrombosis, patency) and histological staining (H&E, Factor VIII, smooth muscle actin). Over the 4-week time period, we observed graft patency and endothelial cell lining of the lumen surfaces. These results demonstrate the feasibility of using silk fibroin as a vascular graft material and some advantages of silk tubes over the currently used synthetic grafts.  相似文献   

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