HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 100/1/76    most recent 00255.2005v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Okere, I. C. Articles by Stanley, W. C. Search for Related Content PubMed PubMed Citation Articles by Okere, I. C. Articles by Stanley, W. C.

Differential effects of heptanoate and hexanoate on myocardial citric acid cycle intermediates following ischemia-reperfusion

Departments of ¹Physiology and Biophysics and ²Nutrition, Case Western Reserve University, Cleveland, Ohio

Submitted 4 March 2005 ; accepted in final form 30 August 2005

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.

anaplerosis; fatty acids; heart; metabolism; mitochondria; pyruvate dehydrogenase

This article has been cited by other articles:

				R. Gelinas, F. Labarthe, B. Bouchard, J. Mc Duff, G. Charron, M. E. Young, and C. Des Rosiers Alterations in carbohydrate metabolism and its regulation in PPAR{alpha} null mouse hearts Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1571 - H1580. [Abstract] [Full Text] [PDF]