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Articles in PresS, published online ahead of print October 8, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00354.2002
Submitted on August 12, 2002
Accepted on October 6, 2002
1 Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, USA; Department of Nutrition, Case Western Reserve University, Cleveland, Ohio, USA
2 Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, USA
3 Department of Nutrition, University of Montreal, Montreal, Quebec, Canada
4 Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland, Ohio, USA
5 Department of Nutrition, Case Western Reserve University, Cleveland, Ohio, USA
* To whom correspondence should be addressed. E-mail: hxb8{at}po.cwru.edu.
Normal cardiac metabolism requires continuous replenishment (anaplerosis) of catalytic intermediates of the citric acid cycle. Little is known about the quantitative aspects of propionate as a substrate of in vivo anaplerosis, therefore we measured the rate of propionate entry into the citric acid cycle in hearts of anesthetized pigs. [U-13C3]propionate (0.25 mM) was infused into a coronary artery branch for 1 hr via an extracorporeal perfusion circuit, and cardiac biopsies were analyzed for the mass isotopomer distribution of citric acid cycle intermediates. Infusion of propionate did not affect myocardial oxygen consumption, heart rate, or contractile function. In the infused territory, propionate infusion did not affect uptake of glucose and lactate, but decreased free fatty acid uptake by half (p<0.05). Propionate extraction and uptake were 57.4 ± 3.3% and 0.078 ± 0.009 µmol.min-1 .g-1. Anaplerosis from propionate, calculated from the mass isotopomer distribution of succinate accounted for 8.9 ± 1.3% of the citric acid cycle flux. Propioylcarnitine release accounted for only 0.033 ± 0.002% of propionate uptake. Methylcitrate did not accumulate. Thus administration of a low concentration of propionate appears to be a convenient and safe way to boost anaplerosis in the heart.
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