| Background:Mitral regurgitation model is divided into mitral regurgitation model in small animals,mitral regurgitation model in large animals,mitral regurgitation platform model in vitro according to the source,and into primary mitral regurgitation model and secondary mitral regurgitation model according to the pathogenesis.These models have their own characteristics to provide differential support for clinical research.The large animal model of mitral regurgitation can not only meet the needs of basic research,but also can be used in the research and development of surgical instruments,interventional catheter instruments and pre-clinical evaluation.It is an important tool for cardiovascular research.At present,with the research of the disease mechanism and the development of surgical and interventional instruments,the large animal model of mitral regurgitation has a great demand.The standardized manufacturing process with good consistency and high success rate,as well as the systematic research on the basic data of the model system,is the inevitable requirement for the animal model of mitral regurgitation in the future.In addition,pig has the advantages of high homology with human,similar heart structure,low cost,convenient feeding and management and so on.It is the most widely selected animal in large animal experiment.Therefore,the model of mitral regurgitation in pigs has a wide application prospect.Aims:To establish a model of severe regurgitation of porcine mitral valve with good homogeneity,high success rate and less complications.To study these porcine models of severe mitral regurgitation in a long-term and systematic manner,and to discuss their potential applications in cardiovascular diseases.Methods:17 pigs were divided into experimental group(n=11)and control group(n=6).In the experimental group,the chordae tendinosus in the p2,p3 region of the mitral valve were cut by a self-made chordae tendinous cutter through left thoracic incision-left atrial auricle-mitral orifice approach under the monitoring of epicardial ultrasound and left atrial pressure.During the operation,the left atrial pressure increased by 10 mm Hg and the area of the regurgitation bundle accounted for more than 40%of the left atrium area,which resulted in the formation of a severe mitral regurgitation model.The control group underwent the same procedure as the experimental group but did not damage the chordae tendineae of the mitral valve for sham operation.The model animals were followed up for 30 months.Electrocardiogram,echocardiography,endocardium three-dimensional electrophysiological mapping,atrial fibrillation susceptibility test and myocardial histopathology were measured.Results:The mortality of mitral regurgitation operation was 9%(1/11)and the success rate of the model was 82%(9/11).The ECG showed that the width of P wave increased in the experimental group,and some of the experimental animals showed double-pointed changes.During 30 months after operation,repeated echocardiography was performed in mitral regurgitation group and control group.There were significant inter-group differences,intra-group differences and interactions in left atrial maximum volume,left atrial minimum volume,left atrial ejection fraction between the two groups;no significant inter-group differences,intra-group differences and interactions in left ventricular end systolic volume and left ventricular end diastolic volume between the two groups;significant inter-group differences,intra-group differences but no interactions in left ventricular ejection fraction between the two groups.There was no significant difference in three-dimensional electrophysiological mapping of left atrium between the two groups.There was significant difference in the degree of left atrial fibrosis between the two groups(Collagen volume fraction was 18.1%±3.0%and 1.6%±0.2%,P<0.05),but no significant difference in the degree of left ventricular fibrosis(Collagen volume fraction 2.0%±0.5%and 1.9%,P=0.58).There was a significant difference in atrial fibrillation susceptibility between the two groups(P<0.05).Conclusions:Our method can be used to make a simple and effective porcine severe mitral regurgitation model,which can be used for the pathophysiological study of mitral regurgitation,as well as for the development and preclinical evaluation of instruments for mitral regurgitation.The model can also be used in the study of atrial fibrillation and myocardial fibrosis,but not not suitable in the study of heart failure.Background:Atrial fibrillation is a kind of supraventricular arrhythmias characterized by rapid and disordered atrial electrical activity associated with a certain degree of decline in atrial mechanical function and causing irregular ventricular beats.Atrial fibrillation can be secondary to a variety of cardiovascular or non-cardiovascular diseases.Structural remodeling and electrical remodeling of the heart are considered as the basis for the occurrence of atrial fibrillation.Atrial fibrosis is an important part of atrial structural remodeling and plays an important role in the process of atrial fibrillation.However,the mechanism of atrial fibrosis leading to atrial fibrillation is unclear.In some patients with paroxysmal atrial fibrillation,there is a large amount of fibrosis,while in some patients with persistent atrial fibrillation,there are only slight fibrosis changes.In previous studies,myocardial biopsies were often obtained from a single atrial site and did not reflect the overall condition of atrial fibrosis.Aims:To detect the degree of fibrosis in different areas of atrium,to study the relationship between fibrosis and atrial electrical conduction,effective refractory period,and to explore the effect of fibrosis on susceptibility to atrial fibrillation.Methods:19 pigs were randomly divided into 3 groups:control group(n=6)and experimental group(n＝6).Mitral regurgitation was performed in the experimental group and observed for 3 months(n=7)and 6 months(n=6),respectively.The right atrium of the experimental animals was divided into 6 areas:right auricle,tricuspid isthmus,anterior wall of right atrium,posterior wall of right atrium,entrance of superior vena cava and entrance of inferior vena cava;and the left atrium is divided into 6 areas:left atrial ear,atrial septum,posterior wall of left atrium,top of left atrium,pulmonary vein orifice and mitral isthmus.Results:With the continuation of mitral regurgitation,atrial fibrosis aggravated(3.11%±0.08%in the control group,5.85%±0.42%in the 3-month group and 8.17%±0.23%in the 6-month group,P<0.001),atrial fibrillation susceptibility increased(0/6 in the control group,2/7 in the 3-month group,5/6 in the 6-month group,P<0.05),the effective refractory period was prolonged(220.1±1.1 Ms in control group,244.4±1.4 Ms in 3-month group,289.0 18.9 Ms in 6-month group,P<0.001),the conduction velocity decreased(1.39±0.16m/s in the control group,1.04±0.05m/s in the 3-month group and 0.89 ±0.02m/s in the 6-month group,P<0.001).These pathophysiological changes are uneven in different parts of the atrium.The degree of left atrial fibrosis is higher than that of right atrium(3.83%10.25%vs 8.22%±0.83%in the 3-month group,P<0.001;5.09%±0.34%vs 11.76%±0.52%in the 6-month group,P<0.001);There was a significant difference in fibrosis in different regions of the left atrium(P<0.001,in the 3-month and 6-momth group respectively).The mean conduction velocity of left atrium is lower than that of right atrium(0.86±0.07 vs 1.20±0.32 in the 3-month group,P<0.001;0.62±0.02 vs 1.13±0.03 in the 6-momth group,P<0.001),There was significant difference in conduction velocity in different regions of left atrium(P<0.001,in the 3-month and 6-momth group respectively).The mean effective refractory period of the left atrium is longer than that of the right atrium(238.6±3.1ms vs 251.4±2.9ms in the 3-month group,P<0.001;299.315.3ms vs 280.5±12.4ms in the 6-momth group,P<0.001).Susceptibility to atrial fibrillation is associated with dispersion of left atrial fibrosis.There was a significant negative correlation between atrial fibrosis and atrial conduction velocity,but no significant correlation between atrial fibrosis and atrial effective refractory period.Conclusion:With the prolongation of mitral regurgitation time,the degree of atrial fibrosis increased,and the degree of atrial fibrosis was different among different regions.The increased dispersion of atrial fibrosis may be associated with increased susceptibility to atrial fibrillation.Atrial fibrosis may increase susceptibility to AF by affecting conduction velocity rather than effective refractory periods.Background:Chronic primary mitral regurgitation is the most common valvular disease and its incidence will continue to increase in the coming decades as the population ages.Surgery is the most effective treatment for mitral regurgitation,including mitral valve replacement and mitral valve repair.Optimum timing of surgical intervention is of paramount importance.Premature surgery can reduce the patient’s quality of life and increase complications associated with prosthetic valve and anticoagulation therapy,while too late operation will affect the perioperative safety and long-term prognosis.Surgical indications for mitral regurgitation have been continuously modified,but remains clinically challenging.In chronic primary mitral regurgitation,the left atrium is a severely damaged and often neglected organ.Assessment of left atrial function during mitral regurgitation may provide diagnostic value for these patients.Objective:To evaluate the clinical value of left atrial parameters in chronic primary mitral regurgitation by evaluating the parameters of left atrium in different stages of chronic primary mitral regurgitation.Methods:The study included 133 consecutive mitral regurgitation patients in sinus rhythm,classified into mild-moderate mitral regurgitation and severe mitral regurgitation groups according the degree of mitral regurgitation.Then severe mitral regurgitation group was divided into early-severe group and late-severe group according to the indication of operation.The control group was 30 patients without cardiac disease.The left atrial maximum volume(LAVmax),the left atrial volume before left atrial contraction(LAVp),the left atrial minimum volume(LAVmax)were measured by echocardiography.And then the left atrial dilatation index(LADI)is calculated as:LADI=(LAVmax-LAVmin)/LAVmin x 100%,the left atrial passive emptying fraction(LAPEF):LAPEF=(LAVmax-LAVp)/LAVmax×100%,the left atrial active ejection fraction(LAAEF):LAAEF=(LAVp-LAVmin)/LAVpx 100%,the total left atrial ejection fraction(TLAEF):TLAEF=(LAVmax-LAVp)/LAVmax×100%。Left ventricular end-diastolic volume,left ventricular end-systolic volume and left ventricular ejection fraction were obtained by ultrasound.Tricuspid regurgitation pressure difference or pulmonary artery flow time was used to detect pulmonary hypertension.Patient’s conscious symptoms of cardiac insufficiency was obtained by inquiryResults:Univariate analysis showed that the left atrial volume(including LAVmax,LAVp,LAVmin)increased with the aggravation of mitral regurgitation(P<0.001).The left atrial functional parameters(including LADI,LAPEF,LAAEF,TLAEF)decreased gradually with the aggravation of mitral regurgitation.There were significant differences among the three groups(P<0.001).There was a significant difference in LAVmax,LAVp,LAVmin,LADI,LAAEF,TLAEF between early-severe and late-mitral mitral regurgitation group,but no significant difference in LAPEF between the two groups(P=0.05).Logistic multivariate analysis showed that LADI and LAVp were independent predictors of surgical indications for severe mitral regurgitation.Receiver operating characteristic curve analyses showed that LADI has the highest predictive value,and the area under the curve is 0.91(95%confidence interval,0.858-0.965).When LADI was less than 97%,the sensitivity and specificity were 98%and 67%,respectively.Conclusion:During mitral regurgitation,left atrial volume enlargement and function decrease are correlated with the indications of mitral regurgitation surgery.LADI has good sensitivity and specificity in predicting the indication of mitral valve surgery.Quantitative evaluation of left atrial function by echocardiography can be used as a new index to guide the timing of mitral regurgitation surgery. |
PDF Full Text Request