| Objective:Speckle tracking technique was used to evaluate the changes of right ventricular function in rabbit pulmonary hypertension model induced by rotarine and to explore the mechanism of right ventricular remodeling in rabbit pulmonary hypertension model.Methods:1.Preparation of pulmonary hypertension model rabbits:Firstly,monocrotaline（MCT）was used to construct pulmonary hypertension（PH）model rabbits.34 New Zealand white rabbits were randomly divided into 4 groups.In control1 group,n=6,20ml normal saline was injected subcutaneously into the neck and back;Different doses of MCT were injected subcutaneously into the neck and back of the experimental group.The low-dose group L1 group,n=6,20 mg/kg MCT;Medium dose group M1group,n=10,40mg/kg MCT;High dose group H1,n=12,60 mg/kg MCT.pulmonary artery systolic pressure（PASP）was detected by right cardiac catheterization at week 4.PASP was estimated by echocardiography based on tricuspid regurgitation.CT examination was performed to understand the cardiac morphological changes of experimental rabbits.HE staining was performed on the pulmonary blood vessels of experimental rabbits to observe the pathological changes of the pulmonary blood vessels,evaluate the success of the PH model rabbit modeling,and find out the lowest MCT dose for the PH model rabbits.2.Study on the mechanism of right ventricular remodeling in pulmonary hypertension:In order to understand the effect of different degrees of pulmonary hypertension on right ventricular remodeling in rabbits,42 model rabbits were successfully prepared,and the dose of MCT injected into the neck and back was increased to obtain rabbits with different degrees of pulmonary hypertension.42 model rabbits were randomly divided into two groups.Low dose group L2 group:n=12,60mg/kg MCT;Medium dose group M2 group:n=14,70 mg/kg MCT;H2 group:n=16,80mg/kg MCT.Another 12 healthy rabbits were selected as control group control2 group:n=12,20ml of normal saline was injected subcutaneously into the neck and back.All the experimental rabbits were examined by echocardiography at 4 weeks,5 weeks and 7weeks after administration,respectively,and tricuspid annular plane systolic excursion was measured.TAPSE),fractional area change（FAC）,left ventricular ejection fraction（LVEF）,estimated PASP of tricuspid regurgitation,heart rate（heart rate）HR),left ventricular end-diastolic diameter（LVEDD）,left ventricular end-systolic diameter（LVEDD）,left ventricular end-systolic diameter（LVEDD）LVESD),right ventricular end-diastolic diameter（RVEDD）,right ventricular end-systolic diameter（RVEDD）,right ventricular end-systolic diameter（RVEDD）RVESD).The two-dimensional images were analyzed offline,and speckle tracking echocardiography was applied.right ventricular global longitudinal strain（STE）was measured in model rabbits.RVGLS and left ventricular global longitudinal strain（LVGLS）;At the end of the 7th week,the venous blood of the ear margin was collected and the concentrations of c Tn I and CK-MB were measured.Finally,the experimental rabbits were killed by air embolization.The left ventricular mass index（RVMI）and right ventricular hypertrophy index were calculated,and left ventricular mass index（RVMI）and right ventricular hypertrophy index were calculated.RVHI);HE staining was performed on the free wall of the right ventricle of experimental rabbits to observe the pathological changes of the right ventricular myocardium.The expression of connexin 43（CX43）in right ventricular myocardium was detected by Western blot.Results:1.Preparation of pulmonary hypertension model rabbits:At 4 weeks after modeling,there was no significant difference in right ventricular diastolic blood pressure between the four groups（P>0.05）.There were significant differences in right ventricular systolic pressure,pulmonary artery systolic pressure and pulmonary artery diastolic pressure in H1group compared with control1,L1 and M1 groups（P<0.05）.The echocardiographic results showed that PASP35.71±4.23mm Hg in H1group,and PASP in control1,L1 and M1groups did not exceed 30 mm Hg.Color Doppler showed mild tricuspid valve regurgination in H1 group,but no tricuspid valve regurgination in control1,L1 and M1 groups.The imaging results showed that the main pulmonary artery and the right lower pulmonary artery in H1group were slightly dilated,the transverse diameter ratio of the pulmonary trunk to the aortic trunk was>1,and the right ventricle was slightly enlarged.The imaging findings of rabbits in control1,L1 and M1 groups were normal.The results of HE staining showed that the alveolar of rabbits in the H1 group was significantly damaged,the interstitial lung was accompanied by neutrophil infiltration,the smooth muscle tissue proliferation was obvious,the vascular wall of small pulmonary artery was thickened,and the lumen was narrow,while the pulmonary vascular morphology of rabbits in the control1,L1and M1groups was normal,indicating that the PH rabbit model could be successfully established with MCT60mg/kg.2.Study on the mechanism of right ventricular remodeling in pulmonary hypertension:After successful modeling,at 4 weeks after administration,the PASP of rabbits in L2,M2and H2groups was higher than that in control2 group,and the difference was statistically significant（P<0.05）,while there was no statistically significant difference in PASP among L2,M2 and H2groups（P>0.05）.LVGLS and RVGLS of rabbits in L2,M2 and H2 groups were lower than those in control2 group,and the difference was statistically significant（P<0.05）,while LVGLS and RVGLS of rabbits in L2,M2 and H2groups were not statistically significant（P>0.05）.The results showed that L2,M2 and H2model rabbits had right ventricular injury.At 5 weeks after administration,PASP in L2,M2and H2 groups was higher than that in control2 group,the difference was statistically significant（P<0.05）,among which PASP in M2 group was higher than that in L2 group but lower than that in H2 group,the difference was statistically significant（P<0.05）,indicating that the degree of pulmonary hypertension in L2,M2and H2 groups was successively aggravated;TAPSE,FAC and LVEF in L2,M2and H2groups were decreased 5 weeks after administration compared with 4 weeks after administration,but the difference was not statistically significant（P>0.05）,indicating that right ventricular injury was not detected by conventional ultrasound parameters of right ventricular function in experimental rabbits.Compared with control2group,LVGLS and RVGLS in L2,M2 and H2 groups were decreased,and the difference was statistically significant（P<0.05）;LVGLS and RVGLS in M2group were lower than those in L2 group but higher than those in H2group,and the difference was statistically significant（P<0.05）,indicating that the degree of right ventricular injury in L2,M2and H2 groups was successively aggravated.Spot tracking of right ventricular strain can detect right ventricular injury in experimental rabbits.At 7 weeks after administration,PASP in L2,M2and H2groups was higher than that in control2 group,and the difference was statistically significant（P<0.05）.PASP in M2group was higher than that in L2 group but lower than that in H2group,and the difference was statistically significant（P<0.05）.Compared with control2 group,LVGLS and RVGLS in L2,M2 and H2groups were decreased,the difference was statistically significant（P<0.05）,LVGLS and RVGLS in M2group were lower than those in L2 group but higher than those in H2group,the difference was statistically significant（P<0.05）;There was no significant difference in HR,LVEDD,LVESD,RVEDD and RVESD among the four groups（P>0.05）.At 7 weeks after administration,compared with control2group,CK-MB（creatine kink-MB,CK-MB）,c Tn I（cardiac troponin I,c Tn I）,RVHI and RVMI in L2,M2 and H2 groups were increased,and the difference was statistically significant（P<0.05）.CK-MB,c Tn I,RVHI and RVMI in M2 group were higher than those in L2 group but lower than those in H2 group,and the difference was statistically significant（P<0.05）,which further indicated that the degree of right ventricular remodeling increased with the increase of pulmonary hypertension.HE staining results showed that the myocardium fibers of the New Zealand rabbits in control2 group were arranged neatly,the myocardium of the right ventricle was complete,the cytoplasmic staining was uniform,and the nucleus morphology was normal.Myocardial tissue injury in L2,M2 and H2 groups was manifested as partial cytoplasmic vacuole,disordered myocardial fiber arrangement and hypertrophy of cardiomyocytes.Western-blot results showed that CX43 expression in L2,M2 and H2groups decreased compared with control2group,and the differences were statistically significant（P<0.05）.The expression of CX43in M2 group was lower than that in L2 group but higher than that in H2group,and the difference was statistically significant（P<0.05）,indicating that CX43 expression was related to right ventricular remodeling at PH.Conclusions:1.Right ventricular remodeling occurred in pulmonary hypertension model rabbits,and the degree of right ventricular remodeling was related to the degree of pulmonary hypertension.2.The mechanism of right ventricular remodeling in pulmonary hypertension model rabbits is related to the distribution and expression of CX43 protein in right ventricle.3.Ultrasonic Speckle tracking technology can detect right ventricular functional injury in PH rabbits at an early stage,which may provide diagnostic basis for preventing PH right ventricular remodeling in clinic.Figure[11]Table[9]Reference[115]... |
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