A murine model of aortic regurgitation generated by trans-apical wire destruction of the aortic valve

Abstract

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 ± 15.22 mm/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/dt_max and Ees), and diminished LV compliance (smaller dP/dt_min 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.

Keywords

animal model / aortic regurgitation / eccentric hypertrophy / heart failure / volume overload

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RIGHTS & PERMISSIONS

2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.