High rates of residual fatty acid oxidation during mild ischemia decrease cardiac work and efficiency.
It is unknown what effects high levels of fatty acids have on energy metabolism and cardiac efficiency during milder forms of ischemia. To address this issue, isolated working rat hearts perfused with Krebs-Henseleit solution (5 mM glucose, 100 muU/mL insulin, and 0.4 (Normal Fat) or 1.2 mM palmitate (High Fat)) were subjected to 30 min of aerobic perfusion followed by 30 min of mild ischemia (39% reduction in coronary flow). Both groups had similar aerobic function and rates of glycolysis, however the High Fat group had elevated rates of palmitate oxidation (150%), and decreased rates of glucose oxidation (51%). Mild ischemia decreased cardiac work (56% versus 40%) and efficiency (29% versus 11%) further in High Fat hearts. Palmitate oxidation contributed a greater percent of acetyl-CoA production during mild ischemia in the High Fat group (81% versus 54%). During mild ischemia glycolysis remained at aerobic levels in the Normal Fat group, but was accelerated in the High Fat group. Triglyceride, glycogen and adenine nucleotide content did not differ at the end of mild ischemia, however glycogen turnover was double in the High Fat group (248%). Addition of the pyruvate dehydrogenase inhibitor dichloroacetate to the High Fat group resulted in a doubling of the rate of glucose oxidation and improved cardiac efficiency during mild ischemia. We demonstrate that fatty acid oxidation dominates as the main source of residual oxidative metabolism during mild ischemia, which is accompanied by suppressed cardiac function and efficiency in the presence of high fat.
Folmes
Clifford D L
CD
Cardiovascular Research Group and Departments of Pharmacology and Pediatrics, University of Alberta, Edmonton, Alberta, Canada. cfolmes@ualberta.ca
Sowah
Daniel
D
Clanachan
Alexander S
AS
Lopaschuk
Gary D
GD
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D003999:Dichloroacetic Acid / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism
D000227:Adenine Nucleotides; D005227:Fatty Acids; D010168:Palmitates; D014280:Triglycerides; D006003:Glycogen; D003999:Dichloroacetic Acid; D005947:Glucose