经心腔内超声引导二尖瓣反流大动物模型的构建及心脏重塑研究OA

Objective To establishing an animal model of mitral regurgitation(MR)to optimise the entire modelling process based on the transcatheter approach,with the goal of constructing a mini-mally invasive,highly successful,and uniform large animal model of severe MR.Methods Sixteen adult male small-tail Han sheep were randomly assigned to the experimental group(MR group,n=11)or sham-operated group(Sham group,n=5)by a random number table method.In the MR group,under real-time guidance of intracardiac echocardiography(ICE),the mitral chordae tendineae were transected using a disposable biopsy forceps via the carotid artery approach.Successful modelling was defined as a ratio of regurgitant jet area to left atrial area(RJA/LAA)＞40％by colour Doppler imaging.All experimental animals were followed up for 12 weeks postoperatively,with emphasis on assessing the degree of regurgitation and the remodelling process of the left atrium and left ventricle.At the end of the follow-up period,necropsy was performed to examine gross morphological changes of the chordae and valve leaflets,accompanied by pathological evaluation of cardiomyocyte morpho-logical alterations and myocardial interstitial fibrosis.Results Severe regurgitation was successfully established in all 11 small-tail Han sheep in the MR group under ICE guidance.Except for one ani-mal that died of pulmonary oedema secondary to congestive heart failure at the 9 th week postopera-tively,all others survived at the 12-week follow-up endpoint.Follow-up echocardiography revealed typical flail motion of the affected valve leaflets,and the severity of regurgitation remained at a se-vere grade at all follow-up timepoints.In terms of cardiac remodelling,the left atrial diameter(LAD)in the MR group showed progressive enlargement from immediately after surgery,whereas left ventricular end-diastolic volume(LVEDV)and left ventricular end-systolic volume(LVESV)increased significantly from the 4th week postoperatively,and left ventricular ejection fraction(LVEF)declined at the 12th week.Electrocardiography demonstrated wide or bifid P waves.Cardi-ac dissection revealed favourable locations of chordal rupture in the MR group.Pathological findings showed cardiomyocyte hypertrophy and vacuolar degeneration in both the left atrium and left ventri-cle,accompanied by prominent myocardial interstitial fibrosis in the left atrium.Conclusion This study successfully establishes a reliable and stable large animal model of severe MR under ICE guid-ance,which faithfully simulates the cardiac remodelling process induced by MR.This model can be applied to preclinical evaluation of transcatheter mitral intervention devices and investigations into related pathophysiological mechanisms,providing an ideal translational research platform for the di-agnosis and treatment of MR.