Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

A reduction in blood flow to the heart (termed cardiac ischemia) or an imbalance between oxygen supply and oxygen demand causes anginal pain and depresses the normal pump function of the heart. Severe reductions in blood flow may cause a heart attack (termed myocardial infarction). Following a heart attack, the heart cells can be saved from dying by the speedy restoration of blood flow (termed reperfusion). This can be achieved with "clot-buster" drugs, by the placement of stents at the site of blockage, or by surgery. Although these types of reperfusion are beneficial and prevent heart cells from dying, there may be a delay before the heart is able to pump normally. This depression of pumping ability soon after re-establishment of blood flow (in the period termed early reperfusion) reduces the clinical benefits of reperfusion, increases adverse effects, prolongs hospital stays and increases health care costs. We have determined that one of the factors that contributes to poor recovery of contractile function is a high rate of acid production that causes ionic imbalances in the heart cells. The heart must use some of its energy to restore normal ion levels and it does this by diverting energy away from contractile functions. This causes the heart to become inefficient in the use of energy for pumping activity and so slows the return of normal contractility. We will determine reasons for the upset in cardiac metabolism that is responsible for the production of the acid and will explore mechanisms that could be used in the design of drugs that might improve heart function in the critical early period of reperfusion. We plan to study the effects of controlling glycogen (carbohydrate storage form) metabolism on reducing acid production and potentially protect the heart. Also, we plan to study the effects of adenosine, which is released in the heart as a defense mechanism, on glucose and glycogen metabolism and the subsequent protection of the heart.