Grant: Project Grant

Heart diseases remain 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) owing to ventricular tachycardias (VTs), abrupt accelerations of heart rate which precede cardiac arrest and death. Most victims of SCD were not identified as high risk individuals and could not be protected by specific drug treatments or implantable medical device (defibrillator). This unacceptable situation is the direct consequence of our poor understanding of what exactly triggers VTs. Our research addresses 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 complications of heart attack (myocardial infarction; MI). The origin of VTs is attributed to abnormal electric signals from the cells (Pcells) that compose the "electric wires" of the heart. Experimental animal models showed that electric properties of these "wires" are affected after MI due to an abnormal elevations of calcium (Ca2+) in Pcells. The first goal of the project is to identify abnormal proteins responsible for these Ca2+ elevations in Pcells after MI. The second goal is to understand how cell death in the cardiac wall during MI affects these proteins in Pcells. Experiments will be conducted on Pcells of pig heart. Advanced technical approaches including predicting abnormal Ca2+ activity in Pcells by a computer program will be implemented to identify the "triggers" of the process leading to SCD. The project is anticipated to provide clinically measurable indicators of the risk of VT and to identify new avenues for (so far nonexistent) specific treatments of patients at risk of SCD. The impact of MI will be investigated in males and females to evaluate the sex-differences in the risk of SCD.