Research Of Turbulent Shear Stress Effect To Valve In The Flow Field Of The Heart Valve

Objective:We build the Mitral Stenosis(MS),Mitral Regurgitation(MR),Aortic Stenosis(AS),Aortic Regurgitation(AR)model of pig to provide basis for further studying the relationship between cardiac valve area hemodynamic abnormalities and cardiac valve progressive lesion.Methods:1.The all cases of Diannan pig were divided into group MS,group MR,group AS,group AR,and control group.We build the MS,MR,AS animal model through the ways of artificial controlled mechanical ventilation,the sternum midline incision thoracotomy,and Cardiopulmonary bypass(CPB).We build the AR animal model through the ways of Intravenous anesthesia than artificial mechanical ventilation,carotid artery puncture,and endovascular intervention.2.We used echocardiogram to measure mitral valve area(MVA),aortic valve area(AVA),Peak velocity of mitral valve(MVmax),Peak velocity of aortic valve(AVmax),mean mitral transvalvular pressure gradient(MPGmean),mean aortic transvalvular pressure gradient(APGmean)to evaluate the valvular stenosis degree of group MS and group AS at the time of pre-operation,Immediately after operation,4 weeks after operation.We measured the mitral valve regurgitation fraction(RFmv),mitral valve regurgitation volume(MVRV)to evaluate the degree of regurgitation of mitral valve of group MR.We measured aortic valve regurgitation fraction(RFAV),aortic valve regurgitation volume(AVRV)to evaluate the degree of regurgitation of aortic valve of group AR.Results:1.The process of building model of group MS,group MR,group AS,and group AR was going well.In group MR,group AS and group AR,1 case died during the operation.In group MS,1 case died after operation.2.The MVA of group MS after the operation was significantly reduced compared with before,and there was significant difference(P<0.01).The degree of stenosis 4 weeks after the operation was increased compared with the moment after the operation,but the difference was not statistically significant(P>0.05).MVmax and MPGmean after the operation were significantly increased compared with before the operation,and there was significant difference(P<0·01).MVmax and MPGmean 4 weeks after the operation were increased compared with the moment after the operation,but the difference was not statistically significant(P>0.05).3.In group MR,RFMv and MVRV after the operation were significantly increased compared with before the operation,and there was significant difference(P<0.01).The degree of regurgitation 4 weeks after the operation was increased compared with the moment after the operation,but the difference was not statistically significant(P>0.05).4.In group AS,AVA after the operation was significantly decreased compared with before the operation,and there was significant difference(P<0.01).The degree of stenosis 4 weeks after the operation was increased compared with the moment after the operation,but the difference was not statistically significant(P>0.05).AVmax and APGmean after the operation were significantly increased compared with before the operation,and there was significant difference(P<0.01).AVmax and APGnmean 4 weeks after the operation were increased compared with the moment after the operation,but the difference was not statistically significant(P>0.05)..5.In group AR,RFAV and AVRV after the operation were significantly increased compared with before the operation,and there was significant difference(P<0.01).The degree of regurgitation 4 weeks after the operation was increased compared with the moment after the operation,but the difference was not statistically significant(P>0.05).Conclusions:In this study,MS,MR and AS animal models were successfully build under the condition of artificial controlled mechanical ventilation and using the ways of the sternum midline incision thoracotomy and Cardiopulmonary bypass(CPB).We build the AR animal model through the ways of Intravenous anesthesia than artificial mechanical ventilation,carotid artery puncture,and endovascular intervention.The 4 models can be used to simulate the hemodynamic status of human body in four pathological conditions which were MS,MR,AS and AR.The 4 models which were reliable,feasible,stable and reproducible were of great significance for us to further study the relationship between cardiac valve area hemodynamic abnormalities and cardiac valve progressive lesion.Objective:To clarify the relationship between Turbulent Shear Stress(TSS)in mitral stenosis,mitral regurgitation,aortic stenosis,aortic regurgitation and valvular lesions.The aim of this study is to provide a basis for further study on the molecular biology of TSS inducing valvular endothelial cell damage.Methods:1.The established animal models which were group MS(n=4),group MR(n=4),group AS(n=4),group AR(n=4)and control group(n=5)were followed up for 1 year.Echocardiography was performed in all groups before the operation,the moment after the operation,4,8,12 months after the operation.The testing programmes were echocardiography index which included LVEF,LVEDD,LVESD,LAV,MVA,AVA,MPGmean,APGmean,QMV,QAV,RFMV,RFAV,MVRV,AVRV,EROM,EROA and flow field uniformity index which included MVmax,AVmax,?AMVmax,AAVmax.Using color Doppler echocardiography combined with the analysis of image by computer to measured TSS.The difference between the experimental groups and the control group were compared by statistical analysis.2.All animals were executed and the mitral valve and aortic valve were taken out after echocardiography 12 months after the operation.According to the results of TSS test,the valvular tissue which was in case of maximum force was fixed by neutral formalin,was made into paraffin-embedded section,was dyed with HE.After these processes,we observed the valve about pathological changes and remodeling situation under light microscope,about organelle changes under transmission electron microscope.The histological and ultrastructural differences between the experimental groups and the control group were analyzed.Results:1.The changes of LVEF,LVEDD,LVESD and LAV after the operation in the group MS were consistent with the changes of MS pathophysiology.The MVA,MPGmean,MVmax,?MVmax of control group after the operation was better than that of group MS(P<0.05).The indexes except QMv of group MS changed significantly at 8 months after the operation.MVA gradually decreased(P<0.05),MPGmean,MVmax and?MVmax gradually increased(P<0.05),and the flow field uniformity of mitral valve was significantly worse.There was no difference about the TSS in the A4C and A2C core area between the group MS and the control group(P>0.05).There were significant differences about the TSS in the peripheral boundary points between the group MS and the control group(P<0.01),and the TSS in group MS was significantly higher than that in control group.Through correlation analysis,we can know that MVA was negatively correlated with MPGmean(-0.784),MVmax,(-0.743)and ?MVmax(-0.801),and MVA gradually decreased,MPGmean,MVmax,and ?MVmax gradually increased with the elapse of time.There.was no significant correlation between MVA and core site TSS.MVA was negatively correlated with TSS in the peripheral boundary points.With the gradual decrease of MVA,TSS in the peripheral boundary points gradually increased.2.The changes of LVEF,LVEDD,LVESD and LAV after the operation in the group MR were consistent with the changes of MR pathophysiology.RFMV?MVRV?EROM??VMR of group MR were detected at the moment after the operation,but they significantly increased at 12m after the operation(P<0.05).There was no change about TSS in section A4C and A2C core area of group MR at each follow-up time point after the operation(P>0.05).TSS in the peripheral boundary points significantly increased at 12m after the operation(P<0.05),and TSS in the peripheral boundary points was significantly higher than the core site(P<0.05).Through correlation analysis,we can know that EROM was positively correlated with RFMV(0.904),MVRV(0.871)and ?VMR(0.916),no correlation with VMR.With the increase of EROM,RFMV,MVRV and ?VMR gradually increased,but the flow field uniformity becomes worse.There was no significant correlation between EROM and core site TSS.EROM was positively correlated with TSS in the peripheral boundary points.With the increase of EROM,TSS in the peripheral boundary points increased gradually.3.The changes of LVEF,LVEDD,LVESD and LAV after the operation in the group AS were consistent with the changes of AS pathophysiology.The indexes which were AVA,APGmean,AVmax,?AVmax of control group after the operation were better than that of group AS(P<0.05).The indexes except QAV of group AS changed significantly 12m after the operation.AVA significantly decreased(P<0.05),and APGmean,AVmax and AAVmax increased significantly(P<0.05),and the flow field uniformity of aortic valve was significantly worse.There was no difference about the TSS in the section A5C and PL A core area between the group AS and the control group(P>0.05).There were significant differences about the TSS in the peripheral boundary points between the group AS and the control group(P<0.01),and the TSS in group AS was significantly higher than that in control group.Through correlation analysis,we can know that AVA was negatively correlated with APGmean(-0.812),AVmax(-0.845)and ?AVmax(-0.850).With the AVA gradual decrease,APGmean,AVmax and ?AVmax increased gradually.There was no significant correlation between AVA and core site TSS.AVA was negatively correlated with TSS in the peripheral boundary points.With the gradual decrease of AVA,TSS in the peripheral boundary points gradually increased.4.The changes of LVEF,LVEDD,LVESD and LAV after the operation in the group AR were consistent with the changes of AR pathophysiology.RFAV?AVRV?EROA??VAR of group AR were detected at the moment after the operation,but they significantly increased after 12m(P<0.05).There was no change about TSS in section A5C and PLA core area of group AR at each follow-up time point after the operation(P>0.05).TSS in the peripheral boundary points significantly increased 12m after the operation(P<0.05),and TSS in the peripheral boundary points was significantly higher than the core site(P<0.05).Through correlation analysis,we can know that EROA was positively correlated with RFAV(0.913),AVRV(0.920)and AVAR(0.842),no correlation with VAR.With the increase of EROA,RFAV,AVRV and ?VAR gradually increased,but the flow field uniformity becomes worse.There was no significant correlation between EROA and core site TSS.EROA was positively correlated with TSS in the peripheral boundary points.With the increase of EROA,TSS in the peripheral boundary points increased gradually.5.Comparing the results of mitral valve and aortic valve HE staining and transmission electron microscope between experimental group and control group.The tissue of mitral valve and aortic valve in the control group was clear structure,with few cells,and endothelial cell shedding or obvious collagen fiber hyperplasia was not seen in the tissue.Pathological changes were observed in mitral valve tip and the edge of mitral valve tissue of group MS and group MR and in aortic valve tip and the edge of aortic valve tissue of group AS and group AR.The structure of the tissue is not clear,and the collagen fibers and elastic fibers increasing and rupturing could be seen in the tissue.At the same time,the hyaline change,myxoid change,capillary proliferation,drop of endothelial cells,intercellular substance edema could be seen in the tissue.Conclusions:The turbulent shear stress produced by the flow field of mitral stenosis,mitral regurgitation,aortic stenosis,and aortic regurgitation is one of the important factors leading to the progressive damage of the valve.Objective:To detect the expressions of CXCR7 in the valvular tissue where the mitral stenosis,mitral regurgitation,aortic stenosis,aortic regurgitation induced turbulent shear stress.To study on the correlation between turbulent shear stress and CXCR7 expressionMethods:To detect the expressions of CXCR7 and distribution in the valvular tissue where the mitral stenosis,mitral regurgitation,aortic stenosis,aortic regurgitation induced turbulent shear stress by Western Blot,Real-Time RT-PCR and IF methods.By statistical analysis,comparing the difference between the experimental groups and the control group.Results:1.The expressions of CXCR7,mRNA and IF at the tip of mitral valve in group MS were higher than those in the control group,and the difference was statistically significant(P<0.05).2.The expressions of CXCR7,mRNA and IF at the edge of mitral valve regurgitation orifice in group MR were higher than those in the control group,and the difference was statistically significant(P<0.05).3.The expressions of CXCR7,mRNA and IF at the edge of aortic valve in group AS were higher than those in the control group,and the difference was statistically significant(P<0.05).4.The expressions of CXCR7,mRNA and IF at the edge of aortic valve regurgitation orifice in group AR were higher than those in the control group,and the difference was statistically significant(P<0.05).5.In section A4C and A2C of group MS and group MR,the results of TSS of mitral valve area were positively correlated with CXCR7,mRNA and IF.In section A5C and PLA of group AS and group AR,the results of TSS of aortic valve area were positively correlated withCXCR7,mRNA and IF.Conclusions:The expression of CXCR7 was positively correlated with TSS which was in the flow field of heart valve of mitral stenosis,mitral regurgitation,aortic stenosis,and aortic regurgitation.CXCR7 played an important role in the process of continuous cardiac valve lesions induced by TSS.