Mechanisms of Arrhythmogenesis with Altered Ventricular Strain during Acute Regional Ischaemia

The purpose of the heart is to pump blood to the body. This occurs as electrical signals travel through the heart in a regular pattern. A significant number of deaths in Canada each year are caused by a disturbance of this electrical activity (arrhythmias) due to of a blockage in the vessels supplying blood to the heart (regional ischaemia). Research into how arrhythmias occur during regional ischaemia is of great clinical importance as it will enable the development of new therapies. We have shown that changes in the heart's contraction in regional ischaemia contribute to the accompanying arrhythmias. However, it is unknown how this occurs. Thus the goal of this project is to discover how changes in contraction lead to deadly arrhythmias in regional ischaemia. We believe that these arrhythmias are caused by specific changes in cell behaviour due to effects of altered contraction on underlying cellular processes. Experiments will be performed using established techniques involving live hearts from rabbits, whose structure and function is more like the human heart than those from any other small animal. To test our hypothesis, we will measure effects of different changes in contraction during regional ischaemia on the cellular processes of interest using specialised fluorescent dyes. This will be combined with the use of drugs that specifically affect each cellular process of interest. Overall, this research will help us to better understand how arrhythmias occur during regional ischaemia. As arrhythmias during ischaemia are a common disorder that occurs alone and in many heart diseases, this project is directly relevant to a large number of patients. By discovering processes that contribute to these deadly arrhythmias, new treatments may be developed. This ultimately will help to reduce the high incidence of death due to regional ischaemia, thus saving the lives of countless Canadians who suffer from this deadly condition.