| Background and purposes of the research:Clinical of neurosurgeons often encounter patients with fusiform aneurysm orthe wide-neck aneurysm, neck is hard to visualize and may be large, contain thebole branch or the multi-perforating branch of aneurysm, contain theromatousplaque or calcification of aneurysm, as well as the aneurysm neck bursts orfragile so on, both the treatment of endovascular embolization and surgery clippingmanagement dilemmas, significant technical difficulties for management has twoaspects: On the one hand, the incompletely clipped aneurysms with neck remnants orthe sack embolism incomplete, and the re-bleed, recurrence, regrowth are knownto occur. On the other hand, occlusion the bole branch artery to result in partlycerebral ischemia or cerebral infarction and can be fraught with life-threateningcomplications. In addition, both the endovascular embolization and surgery clippingcan not reinforce the thinning aneurysm wall. In case of the management dilemmas,only had to choose the external wrapping.Initially, muscle and muslin (cotton) gauze was the most common wraps used toreinforce the aneurysm wall. assessing long-term efficacy of wrapping, however,muscle was easy tended to become necrotic, and then absorbed within 2 months.muslin was at times evoked undesirable side effects such as visual failure, cranial nerve palsies and infection. In addition, Wrapping techniques and facilities availablealso has the insufficiency that need for complete exposure of the aneurysm withoutprecipitating rupture was onerous.Over time the wrapping techniques were improved by many scholars undertakena lot of experimental animal studies. Different product options were explored; theapproved product had the encircling Dacron-covered metal clips (Sundt type) andwrap-clipping with a Dacron mesh silastic sheet (Fujitsu type). However,thedisadvantage of Sundt clips is that the diameter cannot be adjusted to the outerdiameter of the dissected artery. If the clip diameter is too small the patency of theartery is compromised and if it is too large it cannot stabilize the wall. In another,Fujitsu type were require complete dissection aneurysm and parent artery, In anunstable situation this maneuver may be enough to cause rupture. In addition, Fujitsutype can not prevent further the cuffs gliding movement and clips slip. and there-bleed, recurrence, regrowth re known to occur. Uhl etal developed a methodthat used fenestrated angled clip to carry wrapping material around artery, but theeffect was not still ideal.In addition, these 3 kind of wrap-clipping with synthetics material sheet that inpoor of histocompatibility,security and ductility, which can not degradation andabsorption in long-term, at times it evoked undesirable side effects such asgranulomatous reaction,host reaction,infection and so on. Well fitting cuffs withperfection of nature is the key point of the wrapping treatment.The long-term curative effects of the wrapping treatment aneurysm in poor wasdue to two aspects: the first, the nature of wrap materials was not ideal, whichinduction of serious side effect can be fraught with life-threatening complications, thesecond, wrapping techniques were not flawless, especially in the match of cuffs andthe cuffs gliding movement and clips slip. If the insufficiency can be overcome, thetreatment of aneurysm by the external wrapping means may perhaps prove to be morepromising in the future.In view of these side effect and complications of the wrapping treatment aneurysm, we undertaken to analyze the mechanism of formation, development andto rupture in the fusiform aneurysm by means of venous auto graft canine models.application the biological graft that advanced development and exploitation byregeneration medical engineering to carry out the external wrapping treatment incompletely match state, approach and analysis the long-term curative effects of thewrapping treatment aneurysm by observe the characteristic change of homodynamicand histological in canine models after the wrapping treatment. And assessing thelong-term turnover of biological graft.Approach and analysis the most ideal material in the long-term curative effectsof the wrapping treatment aneurysm by compare observe the characteristic change ofhomodynamic and histological in canine models after the wrapping treatment, ofbiological graft, e-PTFE,Dacron and venous auto et al four kind of materials.In view of these side effect and complications, we undertaken to advanceddevelopment and exploitation the neotype of encapsulated aneurysm clip withbiological graft across the vessels, which successfully solves the problems ofboth unreasonable encapsulated materials and techniques, And assessing thelong-term curative effects of the wrapping treatment aneurysm by animal experimentand clinical application.Materials and methods:Part one: Establishment of fusiform aneurysm in venous auto graft canine models,observation of aerodynamics versus histology.1. Establishment of animal research model: external jugular vein of strip tunicaexternal grafting the defect of carotid artery in 1.5cm by microsurgeryanastomoses at double side for establishes the model of fusiform aneurysm.2 Detection of haemodynamics: 10 dogs are randomly order numbers,respectively take 4 dogs in 4th days, 6 week, 13 weeks after the operation tocarry out digital subtraction angiography, observe the shape, smooth, form ofblood flow and measure the parameter of blood vessel, calculate the detention time of constrast medium in cavity of aneurysm, each dog in 2nd,4, 12 weeksafter the operation to carry out examination of Doppler ultrasound, observe theform of blood flow, frequency spectrum, parameter of blood vessel and bloodflow, thickness of plaque.3 Observation of histologicah: respectively take 3 dogs in 6th, 9, 13 weeks after theoperation to carry out dissect in general anaesthesia, observe the appearance invivo, the histological characteristics of light microscope and ultramicrostructure of transmission electron microscope.Part two: Study of haemodynamics versus histology at fusiform aneurysm with thewrapping treatment of biological graft in venous auto graft canine models1. Model of wrapped in completely match state establishment and experimentgroups: 5 dogs by microsurgery anastomose at double side carotid artery forestablish the model of fusiform aneurysm in 10 cases. The left side wrappingwith the biological graft as experiment group in 5 cases, tubiform inner diameterafter wrapped to match outer diameter of carotid artery, the scope of wrappedincle span of fusiform aneurysm+far and near end carotid artery respective in0.5cm. The left side as control group in 5 cases.2 Observation of haemodynamics versus histology: 5 dogs in 6 months after theoperation to carry out examination of Doppler ultrasound, respectively take 1dogs in 6th, 9, 12, 18,24 months after the operation to carry out digitalsubtraction angiography and Doppler ultrasound observation of haemodynamics,and then follow to dissect in general anaesthesia, observe the appearance invivo, the histological characteristics of light microscope and ultra microstructureof transmission electron microscope.Part three: The control study of 4 kinds of materials wrap in fusiform aneurysm.1 Model establishment and experiment groups: 20 cases of fusiform aneurysm at 3months after the operation by microsurgery anastomose at double side carotidartery in 10 dogs. Divided into 4 groups according to contrast principle of the same dog's two side's models at different groups. Each group in 5 cases. Refersto the method of the second part, uses 4 kinds of materials to carry out wrapcontrast, group A wrapping with biological graft, B with venous auto, C withe-PTFE, and D with Dacron.2 All dogs in 1th,3,6, 9, 12, 18,24 months after the operation to carry out Dopplerultrasound observation of haemodynamics, respectively take 2 dogs in 6th, 9,12, 18,24 months after the operation to carry out digital subtraction angiographyobservation of haemodynamics, and then follow to dissect in generalanaesthesia, contrast observe the appearance in vivo and the histologicalcharacteristics of light microscope.Part four: Development and clinical application of the neotype of encapsulatedaneurysm clip with biological graft across the vessels.1 Designs the structural pattern of neotype encapsulated aneurysm clip withbiological graft across the vessels according to the request of clip,wrapping,antiskid, gluing and fixing the biological graft at dentes of Palatine by means ofindentation oppression.2 Animal experiment: 10 cases of fusiform aneurysm at 3 months after theoperation by microsurgery anastomose at double side carotid artery in 5 dogs.The left side wrapping-clip application the neotype of encapsulated aneurysmclip with biological graft across the vessels wrapping with the biological graftas experiment group in 5 cases, The left side as control group in 5 cases.respectively take 1 dogs in 6th, 9, 12, 18,24 months after the operation to carryout Doppler ultrasound and digital subtraction angiography observation ofhaemodynamics, and then follow to dissect in general anaesthesia, contrastobserve the appearance in vivo and the histological characteristics of lightmicroscope in two side model.Clinical application:6 cases of cerebral intractable aneurysms encounter inclinical patients to carry out wrapping-clip with the Fenestrated angledclip-biological graft, observation their clinical state after the operation, follow-up and recheck with digital subtraction angiography and observation the change ofhaemodynamics.Results:Part one:1 All these 10 dogs were survivorship with normal respond and activity, 20 casesof model with good shape of fusiform aneurysm and none spontaneous rupturein3 months.2 The eddy was occurrence in intracavity of fusiform aneurysm with the colormosaic of blood stream and had the distinctive eddy spectra's of double phase.the speed of constrast medium suddenly to quicken when pass the near endstoma and majority of direct inflows distally carotid artery while minority hits thesidewall of far-end stoma and returns flows, high speed revolves, forms theeddy current, the constrast medium to be detained obviously.3 Parameter of blood vessel: The length of fusiform aneurysm to shorten as time tolengthen, the width of fusiform aneurysm to expand as time to enlarge, The farand near end inside diameter of fusiform aneurysm to shorten as time to lengthen.and reexpand at 3 months tend to the inner diameter of carotid artery, the plaquethickening in 4～6 weeks and organize thinningz in 13 weeks.4 Blood stream parameter: Vs suddenly to speed up when through the near endstoma and then obviously to reduce as enters the lump cavity, the Vd of the nearend stoma and the mesotropic obviously exceed the far end stoma. And the RI offar and near stoma higher than others, the mesotropic is lowest.5 Characteristic of morphology: The shape of aneurysm was fusiform and hadmadder red week wall, hyperplasia of plaque at far and near stoma, compensationincreasing of neighbor artery, the wall thinnest at central part and had thehemorrhage phenomenon.6 Characteristic of histological and ultra microstructure:①Damage primarily in 69 weeks: endothelial cell damage, denudation or vacuole denaturation,thickening of inner membrane and thrombus glutinous the wall, the smoothmuscle cell migration and suffers injury, multiplication and vacuolar degeneration, hyperplasia of plaque stoma, tunica media fiber disrupt. Organizeand remodeling primarily in 13 weeks: organize thinningz of inner membrane,endothelial cell cytothesis obviously, hyperplasia and thinningz of plaque stoma,tunica media fber multiplication, organize and thinningz.②Tunica media fiberoscillates disrupt and inflammation organizes, the smooth muscle cell suffersseverity injury and structure of the nucleus blur, intracytoplasm cell organelledecrease and degeneration, fibroblast multiplication and remodeling the wall bymeans of swallow proceedings.③Inflammatory cell infiltration keep on exist andmacrophage active to swallow, foam cells and lip doses multiplication step bystep.④Newly born uter membrane to form by hyperplasy of collagen fibrils.Part two:1 All these 5 dogs were survivorship, normal respond and activity in 4 cases, 4thdog appear powerless of the upper and lower legs at left side. And combine dullof reaction.2 Characteristic of haemodynamics: The gules of lamina flow replaces the colormosaic of eddied flow and had the one-way spectra of lamina flow in aneurysmintracavity after wrapping. The Vs,Vd,RI were similar to carotid artery (*P＞0.05), contrast medium through fast without remains by display of digitalsubtraction angiography. However, the intracavity of aneurysm without wrap wasthe color mosaic of eddied flow and the contrast medium was detained obviously.The 4 th dog nonvisulization in 18 th months.3 Characteristic of morphology:Aneurysm wrapping with biological graf:①The shape, thickness andtenacity et al of aneurysm matching with carotid artery and the biological grafimpossible abruption from the wall, the inner membrane smooth and glossy.②Astime to lengthen, the micrangium on the superficial of wrapped biological graf toincrease gradually, the ductility and elasticity approximation to carotid arterygradually.Aneurysm model.①the shape of aneurysm was fusiform and had madder red weak wall, hyperplasia of plaque at far and near stoma, the wall thinnest atcentral part and had the hemorrhage phenomenon.②As time to lengthen, the sizeof aneurysm to enlarge step by step, the tenacity of the wall degrade and touchcalcification and induration partial.③The occlude aneurysm of 4 th dog enlargeobviously and sticking by inflammatory reaction on surface, the branch stemthickening obviously at far end. The thickness uneven of the wall and hadhemorrhage, swell, partial to rupture and thrombus attach to wall and organize.There had multistrata of obsolete and fresh thrombus in cavity, the stretchthrombus appear in the near end artery.Characteristic of histological and ultra microstructure:Aneurysm wrapping with biological graf:①The endothelial cell integrity,inner membrane remodeling neither plaque at stoma nor oscillate- abruption atabruption in 6 months, The fibroblast of migratory disruption and release manygrana which contain collagenase to infiltrating tropocollagen, result in activationof tropocollagen and form the chain collagenous fiber of helical configurationmeanwhile to induce hyperplasia and circumvolution of self collagenous, the newvessels can be seen at interspaced. This phenomenon all the more obviously in the9 month after the wrapped.②In 12th month, the chain collagenous fiber ofhelical configuration degeneration decompose loss helical configuration andtransform flow mark collagenous fiber which contain collagenase to infiltrating,meanwhile it mix together with self collagenous fiber and the new vesselsincrease.③In 18th month, the flow mark collagenous fiber degradation andin-growth of fibroblast and smooth muscle cell with distinct cell nucleus, thephenomenon of fibroblast "swallow" and "synthesis- exocytose" obviously.④In 24th month, the inner membrane thinness and rule, the tunica mediaremodeling that fiber rule and tight, the biological graf degradation and replace bycollagenous fiber with "light- dim" alternation periodicity transverse striation,their interspaced in-growth of fibroblast, smooth muscle cell and new vessels. Model of aneurysm:①In 6 th month, endothelial cell stripping or vacuolardegeneration, the sub endothelial layer form continuous capillary, the wall ofaneurysm organize remodeling and inflammatory cell infiltration, the innermembrane foam cells and lipidoses increase, the tunica media "fiber disrupt-hemorrhage", smooth muscle cell cytoreduction and fibroblast cell multiplication,the phenomenon of fibroblast "swallow" and "synthesis- exocytose"obviously.②As time to lengthen, this phenomenon all the more obviously, thewall of aneurysm remodeling and thickness uneven, at the same time, the wallorganize, calcification, elasticity to descend obviously.③inner membrane andtunica media of occlude aneurysm inflammation, organize, burst apart and so on,the wall hemorrhage again and again as well as haemosiderin cell aggregation,there had multistrata of obsolete and fresh thrombus in cavity.Part three:1 All these 10 dogs were survivorship, normal respond and activity in 6 cases, 4dogs appear powerless of the upper and lower legs at one side and combine dullof reaction.2 Characteristic of histological and haemodynamics:Group A: aneurysm wrapping with biological graf, the gules of lamina flowreplaces the color mosaic of eddied flow in aneurysm intracavity. The shape,thickness and tenacity et al of aneurysm matching with carotid artery and thebiological graf impossible abruption from the wall, the inner membrane smoothand glossy. As time to lengthen, the micrangium on the superficial of wrappedbiological graf to increase gradually, the ductility and elasticity approximation tocarotid artery gradually. The tunica media none "fiber disrupt- hemorrhagehemorrhage",Group B: the shape, blood flow parameter of model approach carotid artery in1 st month, the shape of model transform to fusiform and eddy in intracavitary,thesize to enlarge step by step in 3th month, and blood flow parameter hadsignificant difference that compare with control group (*P＜0.05,**P＜0.05).The surface of wall had enlargement blood-supply, the internal of wall hadhemorrhagic focus and endothelial cell damage fall off, inner membranethickening as well as foam cells and lipidoses increase. The tunica media "fiberdisrupt- hemorrhage" obviously. the external jugular vein of wrapping degradationand fiber disrupt, inflammatory cell infiltration and calcification.Group C:the cavity of aneurysm coarctation and show up the crinkle fillingdefect at inner wall, the gules of lamina flow replaces the color mosaic of eddiedflow in aneurysm intracavity and blood flow rate higher than control group. Thenear end of carotid artery collateral circulation to increase; the surface of the wallrigidity, sticking and inflammatory reaction, endothelial cell damage fall off,inner membrane, tunica media thickness uneven and fibrosis. The materials ofe-PTFE none degrdn, internal without in-growth of micrangium beside slightfibroblast and inflammatory cell but extensive calcification and calculus. Occludemodel hyperplasy of stoma and random color thrombus intracavitary.Group D: lumina collapse flattening and blood flow rate increase. The walldense sclerosis and surface inflammation sticking.2 cases occlude in 2 month, andtogether 4 cases occlude within 6 months, its inner membrane destroy and fiberexposed, thrombus scarring. The cavity abnormity enlargement and appear eddy.The endothelial cell damage fall off, inner membrane thickening as well as foamcells and lipidoses increase, inner membrane destroy and fiber exposed, thrombusscarring and inflammatory cell infiltration.Part four:1 Advantageous of encapsulated aneurysm clip with biological graft across thevessels:①gluing and fixing the biological graft at dentes of Palatine by meansof indentation oppression, keep the satisfactory paratope. Clip together withbiological graf perfect matching, the capability of wrapping-clip to getenhancement, prevent the cuffs gliding movement and clips slip efficacious.②the spring ring lock delicate without dodge visual line and semitransparent ofbiological graft look steadily at procedure that the diameter of biological graft can be adjusted to the outer diameter of the aneurysm until wrapping incompletely match state.③the physical chemistry nature of biological graft wassimilar to vessel wall of mankind that stress of mechanical was lower can smoothwrap molding.④the devise reasonable and had a series of type that canwrapping-clip different of angle, size and shape aneurysm.⑤the power of clipappropriate that can tolerate many times adjusted but the elasticity nonedecrescence. The wrap-clip without magnetism and not influence theexamination of CT or MRI at post-operation.2 The gules of lamina flow replaces the color mosaic of eddied flow and had theone-way spectra of lamina flow in aneurysm intracavity with color Doppler afterwrapping. The contrast medium through fast without remains by display ofdigital subtraction angiography. Aneurysm wrapping with biological graf: Theshape, thickness and tenacity et al of aneurysm matching with carotid artery andthe biological graf impossible abruption from the wall, the inner membranesmooth and glossy, the micrangium on the superficial of wrapped biological grafto increase gradually, the ductility and elasticity approximation to carotid arterygradually, and none appear the cuffs gliding movement and clips slip efficacious.The link of across the vessels and the dentes of Palatine perfect matching withcarotid artery, without buckling and narrow of vessel. The dentes of Palatineencasement with hyperplasia fiber and binding with vessel wall withouthemorrhage and inflammation phenomenon. The construction of aneurysm wallrules that inner membrane smooth and glossy non-hemorrhage non-inflammatoryreaction. Biological graf multistrata degradation and induce the in-growth andfusion of cell, fiber and micrangium.3 6 cases of cerebral intractable aneurysms encounter in clinical patients to carryout wrapping-clip with the Fenestrated angled clip-biological graft were getfollow-up and demonstrate that aneurysm disappear but parent artery easy andsmooth by recheck with digital subtraction angiography. The effectiveness ofwrapping-clip were Satisfaction, clinical state fineness in 5 cases besides lightly physical disability inl case (logagnosia without improve correlate with clinicalstate in poor Preoperative), none serious physical disability and none death.Conclusions1 The haemodynamics and histology characteristics of. fusiform aneurysm invenous auto graft canine models conformity with mankind intracranial aneurysm.The key point of formation, development and to rupture in the fusiformaneurysm was eddy formation and hypos-stress of arterial blood. The pathbiology characteristics of fusiform aneurysm canine models were the walladaptability remodeling of haemodynamics. The path biology foundation ofthe fusiform aneurysm development or rupture was that the wall thinningz offiber abruptly inflammation organize and the wall brittleness increase ofinflammatory cell infiltration lipidoses foam cells lipidoses increase by theoscillation effectiveness of eddy.2 The mechanism of formation development in the fusiform aneurysm by means ofvenous auto graft canine models was conformity with mankind intracranialaneurysm, and that exist the danger of unceasing development and to rupture.This model was an ideal aneurysm models for study of wrapping treatment withthe long-term reliability and safety. The wrap method of completely matchingstate to cause the haemodynamics alteration of fusiform aneurysm whichconformity with normal carotid artery. The materials of wrapped to providesatisfactory support for repair of aneurysm wall. Meanwhile it relieve the stressdamage of haemodynamics. the construction of aneurysm wall was more rule andreasonable by the "swallow" and "synthesis- exocytose" action of fibroblast. Theprotein collagen of animal was the fundamental of biological graft that hadperfection mechanical function and biocompatibility. It can provide good supportfor history-regeneration with stable sticking and without reject reaction in thenear stage, on the other hand, it can be completely degradation absorption andsynchronization vicariousness fuse by antilogous tissue in long-term. 3 Compare with the nature of four kinds wrapped materials: The biological grafthad perfection mechanical function and biocompatibility, multistrata degradationabsorption and induce in-growth fusion of auto allergic histiooytic withsynchronization positive matching, e-PTFE had good mechanical function andbiocompatibility, however, it can not degradation absorption and stiffen as wellas induce calcification and concrement in long-term. Dacron's construction wasgood in-growth of histiocyte, but it's supporting structure dysplasia and easy tocollapse deformation, meanwhile, it can not degradation absorption and hadserious inflammatory reaction. Autos venous had good biocompatibility at earlyphase, however, it easy to initiative degrades and mechanical strength descendsstep by step result in effectiveness of wrapped in poor.4 Encapsulated aneurysm clip with biological graft across the vessels canconvenient to carry out wrapping in completely matching state and prevent thecuffs gliding movement and clips slip efficacious. The biological graf at dentes ofPalatine can efficacious reinforce the weak wall of aneurysm. On the other hand,it can be completely degradation absorption and synchronization vicariousnessfuse by antilogous tissue in long-term, effectiveness satisfaction at clinicalapplication.
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