Myocardial oxygen demand and redox state affect fatty acid oxidation in the potassium-arrested heart.
BACKGROUND
Fatty acid (FA) metabolism is suppressed under conditions of cardioplegic arrest, but the mechanism behind this effect is unknown. We hypothesized that alterations in redox state and oxygen demand control myocardial FA utilization during potassium arrest.


METHODS
Rat hearts were perfused with Krebs-Heinseleit buffer containing physiologic concentrations of FAs, ketones, and carbohydrates with unique (13)Carbon labeling patterns. Cytosolic and mitochondrial redox states were altered by manipulating the lactate/pyruvate and ketone redox couples, respectively. Myocardial oxygen consumption was increased by adding the mitochondrial uncoupler 2,4-dinitrophenol to the perfusate. Experiments were conducted under conditions of normokalemic perfusion and potassium cardioplegia (PC). Substrate oxidation rates were derived from (13)Carbon isotopomer data and myocardial oxygen consumption.


RESULTS
Continuous perfusion under conditions of potassium arrest dramatically reduced fatty acid oxidation. Both the addition of 2,4-dinitrophenol and alteration of mitochondrial redox state significantly increased FA oxidation during PC. In contrast to normokalemic perfusion, altering cytosolic redox state during PC did not change FA oxidation.


CONCLUSIONS
These data suggest that mitochondrial redox state and oxygen demand are important determinants of myocardial FA oxidation during potassium arrest. FA oxidation appears to be regulated by different factors during PC than normokalemic perfusion.
Peltz
Matthias
M
Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center at Dallas, TX 75390-8879,USA.
He
Tian-Teng
TT
Adams
Glenn A
GA
Chao
Robert Y
RY
Jessen
Michael E
ME
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D006324:Heart Arrest, Induced; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005227:Fatty Acids; D000105:Acetyl Coenzyme A; D011188:Potassium