Abstract
A miniature pig model of ischemic mitral regurgitation (IMR) was developed by posterior mitral chordae tendinae rupture and implantation of an ameroid constrictor. A 2.5-mm ameroid constrictor was placed around the left circumflex coronary artery (LCX) of male Tibetan miniature pigs to induce ischemia, while the posterior mitral chordae tendinae was also ruptured. X-ray coronary angiography, ECG analysis, echocardiography, and magnetic resonance imaging (MRI) were used to evaluate heart structure and function in pigs at baseline and one, two, four and eight weeks after the operation. Blood velocity of the mitral regurgitation was found to be between medium and high levels. Angiographic analyses revealed that the LCX closure was 10–20% at one week, 30–40% at two weeks and 90–100% at four weeks subsequent ameroid constrictor implantation. ECG analysis highlighted an increase in the diameter of the left atria (LA) at two weeks post-operation as well as ischemic changes in the left ventricle (LV) and LA wall at four weeks post-operation. Echocardiography and MRI further detected a gradual increase in LA and LV volumes from two weeks post-operation. LV end diastolic and systolic volumes as well as LA end diastolic and systolic volume were also significantly higher in pig hearts post-operation when compared to baseline. Pathological changes were observed in the heart, which included scar tissue in the ischemic central area of the LV. Transmission electron microscopy highlighted the presence of contraction bands and edema surrounding the ischemia area, including inflammatory cell infiltration within the ischemic area. We have developed a pig model of IMR using the posterior mitral chordae tendineae rupture technique and implantation of an ameroid constrictor. The pathological features of this pig IMR model were found to mimic the natural history and progression of IMR in patients.
Highlights
Ischemic mitral regurgitation (IMR) is characterized by the backflow of blood from the left ventricle into the left atrium of the heart [1]
We show that this model clinically mimics IMR disease features found in patients, while avoiding the lengthy time required to detect disease pathogenesis in patients naturally suffering from coronary heart disease induced by mitral regurgitation
A pericardial incision was performed and a 2.5-mm ameroid constrictor was placed around the left circumflex coronary artery (LCX), which resulted in myocardial ischemia in a region supplying blood to the LCX
Summary
Ischemic mitral regurgitation (IMR) is characterized by the backflow of blood from the left ventricle into the left atrium of the heart [1]. The dominate theories for mechanisms underlying IMR include: (i) imbalance of leaflet tethering and closing force, (ii) left ventricular remodeling, (iii) left ventricular dysfunction, (iv) dyssynchrony of the left ventricular electromechanical activity and (v) changes in spatial structure of the annulus [3, 4]. It is still unclear what initiates the degenerative cellular changes in the mitral valve and myocardium that lead to disease. The lack of a reliable mammalian model to study the underlying mechanisms for IMR progression remains a critical issue in the IMR research field
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