Cardiology Online - International Academy of Cardiology
 
»search site
The International Academy of Cardiology is dedicated to the advancement of global research in cardiovascular medicine through the support of scientific meetings and publications.
   Home Page
   Congresses
   Journals
   Organizations
   Institutions
   Books
   Research
   Guidelines
   Discussion Groups
   Webcourses
   Websites
   Job Opportunities
   Contact Us




 

 

 

 


18th World Congress on Heart Disease

 

ENHANCING GLUCOSE OXIDATION AS AN APPROACH TO TREAT 403 HEART FAILURE


Gary Lopaschuk, Ph.D., University of Alberta, Edmonton, AB, Canada

 

Alterations in cardiac energy metabolism contribute to the impaired heart function observed in heart failure patients. The failing heart is both energy compromised, as well as inefficient at producing energy. Defects in the rates of O2 consumption and mitochondrial electron transport activity occur in advanced stages of heart failure, which decrease ATP generation. This results in an increase in glycolysis as a source of ATP production. Unfortunately, while glycolysis increases, the second part of the glucose metabolic pathway, glucose oxidation, decreases because it is a mitochondrial dependent process. As a result, an increased uncoupling of glycolysis from glucose oxidation enhances H+ and lactate production. This can decrease cardiac efficiency, as ATP produced by the heart is directed away from use by the contractile proteins towards use in clearance of the H+ís. One promising strategy to increase cardiac efficiency in the failing heart is to directly stimulate glucose oxidation, thereby improving the coupling of glycolysis to glucose oxidation. This can be achieved with agents like dichloroacetate, which stimulate pyruvate dehydrogenase, the rate-limiting enzyme involved in glucose oxidation, and improves cardiac efficiency and function in the failing heart. Alternatively, glucose oxidation can be stimulated indirectly by inhibiting fatty acid oxidation. Fatty acid oxidation inhibitors such as trimetazidine and perhexiline increase glucose oxidation in the heart, and have been shown to be beneficial in treating heart failure. As a result, enhancing glucose oxidation is a potential novel therapeutic approach to treating heart failure.

 

 

 

©1998-2014 Cardiology Online, Inc. All rights reserved.
Cardiology Online is a registered trademark of Cardiology Online, Inc.
CardiologyOnline.com