Grant: Project Grant

Mitral valve role is to prevent the blood going backward as the heart pumps forward. In many cardiac diseases, the heart enlarges and becomes too big relatively to the valve size. The valve is distorted by the enlarging heart and can't close completely: the blood starts to go backward in the lungs instead of going forward. This condition is called "functional mitral regurgitation" and is a major complication that accelerates the heart disease, increasing deaths and hospitalisations. There is no good treatment available. After a heart attack, a substance named serotonin is released in the blood. We believe that serotonin can interfere with valve adaptation to the enlarging heart by causing abnormal scarring in the valve, and ultimately contributes to the valve leak. Our research goal is to demonstrate that serotonin can interfere with mitral valve function after a heart attack. We want to test a drug named cyproheptadine, which is known to prevent the effect of serotonin in the body. We want to demonstrate that cyproheptadine can prevent abnormal scarring in the mitral valve and ultimately help to prevent mitral valve regurgitation after a heart attack. We will use animal experimentations to answer our questions. Because we want to study conditions similar to what happens in human, we will work with sheep since their heart is of similar size and shape compared with human heart. We will create heart attacks in the animals; one group will be treated with cyproheptadine, and another group will not be treated. We have tested this drug in sheep before and we know it is well tolerated. We will use imaging techniques such as echocardiography, cardiac magnetic resonance and cardiac computed tomography to measure the heart size, valve size and mitral regurgitation in both groups to assess the effects of cyproheptadine. We will also analyse the valves after the experiments to evaluate parameters of valve growth and abnormal scarring