Abstract |
In the normal heart, there is loss of citric acid cycle (CAC) intermediates that is matched by the entry of intermediates from outside the cycle, a process termed anaplerosis. Previous in vitro studies suggest that supplementation with anaplerotic substrates improves cardiac function during myocardial ischemia and/or reperfusion. The present investigation assessed whether treatment with the anaplerotic medium-chain fatty acid heptanoate improves contractile function during ischemia and reperfusion. The left anterior descending coronary artery of anesthetized pigs was subjected to 60 min of 60% flow reduction and 30 min of reperfusion. Three treatment groups were studied: saline control, heptanoate (0.4 mM), or hexanoate as a negative control (0.4 mM). Treatment was initiated after 30 min of ischemia and continued through reperfusion. Myocardial CAC intermediate content was not affected by ischemia-reperfusion; however, treatment with heptanoate resulted in a more than twofold increase in fumarate and malate, with no change in citrate and succinate, while treatment with hexanoate did not increase fumarate or malate but increased succinate by 1.8-fold. There were no differences among groups in lactate exchange, glucose oxidation, oxygen consumption, and contractile power. In conclusion, despite a significant increase in the content of carbon-4 CAC intermediates, treatment with heptanoate did not result in improved mechanical function of the heart in this model of reversible ischemia-reperfusion. This suggests that reduced anaplerosis and CAC dysfunction do not play a major role in contractile and metabolic derangements observed with a 60% decrease in coronary flow followed by reperfusion.
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Authors | Isidore C Okere, Tracy A McElfresh, Daniel Z Brunengraber, Wenjun Martini, Joseph P Sterk, Hazel Huang, Margaret P Chandler, Henri Brunengraber, William C Stanley |
Journal | Journal of applied physiology (Bethesda, Md. : 1985)
(J Appl Physiol (1985))
Vol. 100
Issue 1
Pg. 76-82
(Jan 2006)
ISSN: 8750-7587 [Print] United States |
PMID | 16141384
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Caproates
- Heptanoates
- hexanoic acid
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Topics |
- Animals
- Caproates
(administration & dosage)
- Citric Acid Cycle
(drug effects)
- Heart
(drug effects)
- Heptanoates
(administration & dosage)
- Myocardial Contraction
(drug effects)
- Myocardium
(metabolism)
- Reperfusion Injury
(complications, drug therapy, metabolism)
- Swine
- Treatment Outcome
- Ventricular Dysfunction, Left
(complications, metabolism, prevention & control)
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