Grant: Project Grant

Heart disease remains the first cause of mortality in the world. In Canada, it affects 1.4 million people, taking more than 50,000 lives per year in the country. Half of this mortality is due to heart failure, a progressive deterioration of cardiac contraction. The other half occurs suddenly (Sudden Cardiac Death, SCD), mainly caused by ventricular tachycardias (VTs), an abrupt acceleration of heart rate which precedes cardiac arrest and death. Most victims of SCD were not recognized as high risk individuals and could not be protected by specific drug treatment or implantable medical device (defibrillator). This unacceptable situation directly results from a poor understanding of the conditions that trigger VTs. Our research intends to address this issue. A majority of VTs is associated with structural heart disease (virtually any disease of the heart), and about 40% of VTs arise as a complication of myocardial infarction (MI). Clinical evidence attributes the origin of VTs to abnormal electric signals from the cells (Pcells) that compose the "electric cables" of the heart. Experimental animal models showed that electric properties of these "cables" are affected after MI due to abnormal elevations of calcium (Ca2+) in Pcells. The first objective of the project is to identify dysfunctional molecules in the Ca2+ regulation system of Pcells in heart with MI. The second objective is to understand how the cell death in the cardiac wall during MI affects the Ca2+ regulation of Pcells which are anatomically independent on the zone where the injury occurs. Advanced technical approaches including modeling cells by specific computer programs will be implemented to identify the fundamental conditions that trigger the process leading to SCD. The project is anticipated to provide clinically detectable indicators of the risk of VT and to identify molecular targets for developing (so far, inexistent) selective treatments of patients at risk of SCD.