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Citations to this article

Glucose metabolism distal to a critical coronary stenosis in a canine model of low-flow myocardial ischemia.
P H McNulty, … , G C Cline, G I Shulman
P H McNulty, … , G C Cline, G I Shulman
Published July 1, 1996
Citation Information: J Clin Invest. 1996;98(1):62-69. https://doi.org/10.1172/JCI118778.
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Research Article

Glucose metabolism distal to a critical coronary stenosis in a canine model of low-flow myocardial ischemia.

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Abstract

Myocardial regions perfused through a coronary stenosis may cease contracting, but remain viable. Clinical observations suggest that increased glucose utilization may be an adaptive mechanism in such "hibernating" regions. In this study, we used a combination of 13C-NMR spectroscopy, GC-MS analysis, and tissue biochemical measurements to track glucose through intracellular metabolism in intact dogs infused with [1-13C]glucose during a 3-4-h period of acute ischemic hibernation. During low-flow ischemia [3-13C]alanine enrichment was higher, relative to plasma [1-13C]glucose enrichment, in ischemic than in nonischemic regions of the heart, suggesting a greater contribution of exogenous glucose to glycolytic flux in the ischemic region (approximately 72 vs. approximately 28%, P < 0.01). Both the fraction of glycogen synthase present in the physiologically active glucose-6-phosphate-independent form (46 +/- 10 vs. 9 +/- 6%, P < 0.01) and the rate of incorporation of circulating glucose into glycogen (94 +/- 25 vs. 20 +/- 15 nmol/gram/min, P < 0.01) were also greater in ischemic regions. Measurement of steady state [4-13C)glutamate/[3-13C]alanine enrichment ratios demonstrated that glucose-derived pyruvate supported 26-36% of total tricarboxylic acid cycle flux in all regions, however, indicating no preference for glucose over fat as an oxidative substrate in the ischemic myocardium. Thus during sustained regional low-flow ischemia in vivo, the ischemic myocardium increases its utilization of exogenous glucose as a substrate. Upregulation is restricted to cytosolic utilization pathways, however (glycolysis and glycogen synthesis), and fat continues to be the major source of mitochondrial oxidative substrate.

Authors

P H McNulty, A J Sinusas, C Q Shi, D Dione, L H Young, G C Cline, G I Shulman

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Total citations by year

Year: 2024 2020 2018 2017 2014 2011 2010 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 Total
Citations: 1 1 1 1 2 1 26 3 2 1 3 3 3 3 4 4 2 1 4 66
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