We induced significant ischemia in our model of IMR by implanting an ameroid constrictor

It is still unclear what initiates the degenerative cellular changes in the mitral valve and myocardium that lead to disease. Thus, further studies elucidating the mechanisms involved in the progression of IMR are needed to improve diagnostics and therapies. Furthermore, the lack of a reliable mammalian model to study the underlying mechanisms for IMR progression remains a critical issue in the IMR research field. IMR is associated with a worse prognosis after myocardial infarction and subsequent revascularization. At present, medical therapies are not effective for IMR. A combination of angiotensin-converting enzyme inhibitors and betablockade can indirectly prevent IMR by inhibiting left ventricular remodeling. However, the incidence and severity of IMR cannot be circumvented through this approach. Surgical treatment strategies for IMR also remain limited and ineffective. Mitral valve repair or replacement, restrictive annuloplasty and coronary artery bypass grafting have been widely used as surgical methods for IMR treatment for many years, but the persistence and recurrence rates of mitral regurgitation remain high in these patients. Since treatments for IMR remain controversial, the field has focused on developing animal models to study IMR pathophysiology and test therapeutic approaches for IMR. The reported mortality and complication rate within these models remains high and does not represent the natural history of IMR progression in patients. Our study aimed to develop a pig model of IMR using a posterior mitral chordae tendinae rupture technique and implantation of an ameroid constrictor. 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. We provide an in-depth characterization of the pathogenesis of IMR within this pig model, which includes the impact on blood flow, heart function and anatomical location of the mitral lesion at different time Fingolimod points post-operation. We provide evidence for a novel pig model of IMR that recapitulates the natural history of IMR similar to patients. We further provide a stable, feasible and reproducible technique to induce IMR with a high success rate. This model can be exploited to test new therapies and explore the pathological mechanisms underlying IMR as well as determine the influence of etiologies found secondary to IMR, such as atrial fibrosis, atrial fibrillation, structural remodeling of myocardium and heart failure. Troponins start to rise approximately 4–6 h after the onset of acute myocardial infarction and peak at approximately 24 h. They remain elevated for 7–10 days given the long diagnostic window. It is well accepted that troponin levels contribute to the diagnosis and classification of various types of acute coronary syndromes. Troponins can also be sensitively detected by ELISA and can detect low levels of injury in myocardial tissues.

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