Oral Presentations - Pathology and Laboratory Medicine - University ...

Graduate StudentAbstract # 29Varun V. Saran 1 , Vijay Sharma 2 , Violet G. Yuen 3 , Rich Wambolt 1 , Michael F. Allard 1and John H. McNeill 31University of British Columbia, Department of Pathology and Laboratory Medicine, 2 BMJEvidence Centre, British Medical Journal, London, United KingdomVarun Saranmodulation of cardiac metabolism by beta-blockersduring diabetes: a role in apoptosis signalingBackround/ObjectivesOne cardiovascular complication associated with diabetes mellitus (DM) is a cardiomyopathy that can occur in theabsence of valvular or ischemic heart disease and in normotensive patients with excellent glycemic control. Diabeticcardiomyopathy (DC) begins with asymptomatic diastolic dysfunction and can progress to heart failure if notmanaged. The cardiomyopathy observed may be due to a loss of contractile tissue as a result of apoptosis. Apoptosismay be caused by oxidative stress associated with metabolic and signaling modifications that precedes the developmentof dysfunction.Chronic treatment with beta-adrenergic receptor antagonists (beta-blockers) improve function. Metoprolol andcarvedilol are clinically important beta-blockers that have also been shown to favorably modulate metabolism; inaddition, carvedilol, has been shown to have biologically relevant antioxidant properties. Preliminary in vivo dataindicates that metoprolol can reduce apoptosis in the diabetic heart and improve cardiac output. Currently, there is nospecific treatment for DC. Beta-blockers may serve as a novel treatment optionMethodsWe employed a streptozotocin (STZ) induced rat model of type 1 DM. Animals received a one-time dose of 60 mg/kg body weight and the presence of DM was confirmed by measurement of blood glucose levels 3 days post injection.Two weeks post STZ, osmotic pumps containing -blockers were installed. Metoprolol and carvedilol were deliveredat a rate of 15 and 10 mg/kg/day, respectively. In order to assess the significance of carvedilol’s antioxidant abilities,some metoprolol treatments were supplemented with vitamin C, delivered at 1000 mg/kg/day. A six and eight weektime point were studied to assess changes during the asymptomatic and symptomatic phases of cardiomyopathy.ResultsAnalysis of plasma indicates successful induction of DM, with an approximate 2.5-fold increase in blood glucose levelsin STZ treated rats. Diabetic animals show increased fatty acid oxidation, that was normalized by beta-blockers andvitamin C and a significant reduction in rates of glucose oxidation, partially normalized only by both vitamin C withbeta-blockers. However, animals that were diabetic for six weeks showed no DC as assessed by echocardiography andworking heart perfusion.ConclusionAnalysis of effects of beta-blockers, as well as assessment of protein expression, apoptosis and oxidative stress remains.The eight week time point is in progress.40 2 0 1 0 * P o s t e r P r e s e n t a t i o n s