Stimulation of Carbohydrate Metabolism Reduces Hypothermia-induced Calcium Load in Fatty Acid-perfused Rat Hearts
In the present study we examined the impact of glycolysis and glucose oxidation on myocardial calcium control and mechanical function, of fatty acid-perfused rat hearts subjected to hypothermia and rewarming. One group (control) was given glucose (11.1 mm) and palmitate (1.2 mM) as energy substrates...
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Published in | Journal of molecular and cellular cardiology Vol. 29; no. 2; pp. 527 - 534 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Ltd
01.02.1997
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Subjects | |
Online Access | Get full text |
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Summary: | In the present study we examined the impact of glycolysis and glucose oxidation on myocardial calcium control and mechanical function, of fatty acid-perfused rat hearts subjected to hypothermia and rewarming. One group (control) was given glucose (11.1 mm) and palmitate (1.2 mM) as energy substrates. In a second group glycolysis was inhibited by iodoacetate (IAA, 100μm) and replacement of glucose with pyruvate (5 mM), whereas in the third group glucose oxidation was stimulated by administration of dichloroacetate (DCA, 1 mM) and insulin (500μU/ml). All groups showed a rise in myocardial calcium ([Ca]total) in response to hypothermia (10°C). However, [Ca]totalwas significantly lower both in IAA- and DCA-treated hearts, as compared to controls (2.20±0.22 and 2.94±0.20v3.83±0.29 nmol/mg dry wt.,P<0.025). The reduced calcium load in the treated hearts was correlated with higher levels of high energy phosphates. Following rewarming, control and DCA-treated hearts still showed elevated [Ca]total, whereas IAA-treated hearts [Ca]totalwas not different from the pre-hypothermic value. All groups showed a reduction in cardiac output following rewarming. Furthermore, the control group, in contrast to both IAA- and DCA-treated hearts, showed a significant reduction in systolic pressure. These results show that hypothermia-induced calcium uptake in glucose and fatty acid-perfused rat hearts was reduced by two different metabolic approaches: (1) inhibition of glycolysis by IAA while simultaneously by-passing the glycolytic pathway by exogenous pyruvate; and (2) stimulation of glucose oxidation by DCA. Thus, glycolytic ATP is not an essential regulator of sarcolemmal calcium transport under the present experimental conditions. Instead, we suggest that a change in oxidative substrate utilization in favour of carbohydrates may improve myocardial calcium homeostasis during hypothermia and rewarming. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-2828 1095-8584 |
DOI: | 10.1006/jmcc.1996.0296 |