The Changes Of The Flow Field Of The Atherosclerotic Carotid Artery In Rabbit And Its Effect On Intimia-media Pathology And The Mechanics Parameter

Backgroud and objective:Carotid atherosclerotic stenosis(CASS) is an important risk factor of ischemic Cerebra Vascular Disease(ICVD).One of the mechanism of stroke is vulnerable and rupturable plaque which embolize the distal vessel,or the rough plaque surface form the embolism.The flow of blood can bring the various kinds action of force,that include shear stress, circumferential stress,pressure stress so on.The shear stress is considered that it is a mechanics parameter that the best correlative with the formation of the atherosclerosis and rupture of the plaque.According to the research,that the degree of vessel stenosis exceed 40%can bring dynamics changs.This dynamics changs can influence the stability of the plaque.Literature shows,that the exorbitant shear stress at the upstream of stenosis decrease the secretion of the PDGF and restrained the protein compose of the vessel smooth muscle cell(SMC),meanwhile the cell apoptosis increase,the fibrous cap become thin and tend rupture.So,the hydrodynamics factors in the local of the stenotic artery is reason of the atherosclerosis which show the high pathogenicity.Some author consider that,in the initial stage of brain atherosclerosis,the media SMC division and proliferation,transfer to the intima,secrete the connective tissue matrix, include the collagen fibers,elastic fiber and proteoglycan,to cause the intima thickening, and participate the form of As plaque.Following the development of disease,the vessel lumina stenosis result in the blood flow fashion change and the normal vessel become the bend lumina,which will change direction of blood flow and bring the large pressure strain in the vessel wall by blood flow,thus the circumferential stress increase,vessel wall especially at media injury,media occours atrophy in different degrees.The mechanics character of the vessel wall lie on the media,but the media lie on the character,content and spatial configuration of the collagen fibers,elastic fiber and the SM fiber.artery lumina of the local stenosis not only significantly change the geometry and mechanics character of artery,but also bring blood flow and flow field dissimilation, derivation artery hyperblastosis,and accelerate artery stenosis and As.Then following the development of stenosis,the hydrodynamics factors bring the more and more effect.and result in the severe recirculating system disease.Overseas multicentre prospective research manifested,that the patient with the severe carotid atherosclerotic and stenosis was performed the CEA in the earlier period,can decrease the morbidity of the stroke in a year to the 4.5%.But it bring a number of disbility rate and the death rate,thus most patient unwillingness to accept CEA.Furthermore CEA may bring the major trauma,and it is unsuitable with the high risk and perch stenosis,multi-stenosis,Intracranial and vertebral artery stenosis.Recently following the development of the neuroimaging and the neuro interventional therapy,PTA and stenting has was one after another carried out to therapy CASS,and the brain protective device was manufactured to aim at preventing the cerebral embolism and restenosis,thus the cerebral vascular interventional therapy become reality.PTAS to treat the CASS was generally accepted as a therapy of positive curative effect. But its indcation can not be identification.Some scholar propose,if can the patient of symptomatic or asymptomatic of degree of stenosis 30-69%benefit from the interventional therapy? We think,the change of hemodynamics in the different degree stenosis carotid artery bring different effect on intimia-media pathological and the mechanics parameter changes,thus effect the result of interventional therapy.Accordingly, our experiment has studied that the changes of the flow field in the atherosclerotic carotid artery of rabbit and its effect on intimia-media pathology and the mechanics parameter,conduce to search the optimization treatment opportunity.Methods:1.To establish carotid artery intimia lesion and atherosclerosis model by high cholesterol diet Plus airdrying.2.Japanese White rabbits were randomly divided into blank control group(n=6),sham operation control group(n=6),the pathology group(n=24) and mechanics test group.3.At 2^th,4^th,8^th and 12^th week after operation,the degree of mean blood flow velocity and diastasis vessel inner diameter were measured using Color Doppler Flow Imaging to the pathology group.Meanwhile the vein blood was collected and blood viscosity was measured,the shear stress was calculated by CDFI measuring datum.The degree of artery stenosis was analyzed qualitatively and quantitatively by DSA and computer graphic processing system.Carotid artery samples were reserved and the HE,Masson and immunohistochemically was carried out.Intimia-media ratio,mean integra optical densities(IOD) of media smooth muscle cell(SMC) and collagen were calculated. The control groups were measured after 2^th.4.The mechanical properties were measured on a tensile-testing machine to the mechanical test group.The Elastic modulus,the strength failure and the peak load was measured.stress-strain curve were drawn.The change of different degree of stenosis flow field and intimia-media pathological,the vessel wall mechanics parameter changes were compared.Results:1.The average rates of stenosis were calculated and described as following,2-week group:36.58%±8.53%;4-week group 60.28%±5.08%;8-week group 76.07%±5.35%; 12-week65.58%±8.36%;75%carotid arteries of rabbit have the little ramus.The effect was more satisfying after the ramus been ligated temporarily.48 surgery vessel,incidence rate of plaque by microscope checking up:left 87.5%,right 54%,result showed significant difference.,The rates of severe stenosis of bilateral vessel:left 45%,right 8.3%showed significant difference..2.The typical atherosclerotic plaque showed in surgery group.The fibrous plaque was observed,mean while thickness of media and mean IOD of SMC increased at 2^th week after operation.However,following the increase of the stenosis rate and shear stress,the flow field was changed on the stenotic artery.The pathological morphology showed the character of vulnerable plaque such a large lipid core,thin fibrous cap,and rupture in the shouder of plaque at 4^th 8^th week after operation.The media showed atrophy and became thin,mean IOD of SMC was decreased.Statistic analysis showed significant difference in the 2 week group,compared with other group.Immunohistochemically show,vulnerable plaque CD68 express increase.,and upstream region of the plaque is even more obvious.3.Following degrees of the atherosclerosis,the intima showed proliferation and media showed atrophy and became thin,a mass of collagen tissue proliferated and filled in the smooth muscle cell.Artery elastic modulus and stiffness showed increase and atery compliance showde decrease.Statistic analysis showed significant difference at the 12^th week group,compared with sham operation control group and 2^th 4^th 8^th week group after operation,but it showed no such significant deviations at 2^th week group after operation,compared with sham operation control groupConclusions:1.Through the several improvement on the experiment method,we successfully established a carotid atherosclerosis model induced by cholesterol diet plus air-drying in the rabbit.The part of plaque showed the vulnerable character.The pathological changes and its mechanisms were more suitable for the future research in experimental carotid atherosclerosis.2.75%carotid arteries of rabbit have the little ramus.The effect was more satisfying after the ramus been ligated temporarily.Bilateral carotid arteries of rabbit were treated,but only ramus of left carotid arteries was ligated temporarily.The significant result was observed in the left carotid artery,without increase of mortality.3.Following the degree of stenosis,the flow shear stress increased,turbulent flow emerged and flow field changed at the stenotic artery.The plaque become unstable.The vessel occured remodeling.4.At the early atherosclerotic carotid artery,vessel showed positive remodeling.elastic modulus decreased to adapt to the new mechanical condition.But following degrees of the atherosclerosis,.the content of the artery wall collagen increased,the vessel wall elasticity decreased and stiffness increased.The vessel occured negative remodeling,which suggested that the intervetional treatment be in difficulty.