摘要Background:The mechanisms underlying cardiac remodeling in aortic valvular(AoV)disease remain poorly understood,partially due to the insufficiency of appropriate preclinical animal models.Here,we present a novel murine model of aortic regurgitation(AR)generated by trans-apical wire destruction of the AoV.Methods:Directed by echocardiography,apical puncture of the left ventricle(LV)was performed in adult male C57BL/6 mice,and a metal guidewire was used to induce AoV destruction.Echocardiography,invasive LV hemodynamic and histological examination were conducted to assess the degree of AR,LV function and remodeling.Results:AR mice exhibited rapid aortic regurgitation velocity(424±15.22mm/s)immediately following successful surgery.Four weeks post-surgery,echocardiography revealed a 54.6％increase in LV diastolic diameter and a 55.1％decrease in LV ejection fraction in AR mice compared to sham mice.Pressure-volume catheterization indicated that AR mice had significantly larger LV end-diastolic volumes(66.2±1.5 μL vs.41.8±3.4 μL),reduced LV contractility(lower dP/dtmax and Ees),and diminished LV compliance(smaller dP/dtmin and longer Tau)compared to sham mice.Histological examination demonstrated that AR mice had significantly larger cardiomyocyte area and more myocardial fibrosis in LV tissue,as well as a 107％and a 122％increase of heart weight/tibial length and lung weight/tibial length,respectively,relative to sham mice.Conclusions:The trans-apex wire-induced destruction of the AoV establishes a novel and efficient murine model to develop AR,characterized by significant eccentric LV hypertrophy,heart failure,and pulmonary congestion.