Differential effects of heptanoate and hexanoate on myocardial citric acid cycle intermediates following ischemia-reperfusion
- PMID: 16141384
- DOI: 10.1152/japplphysiol.00255.2005
Differential effects of heptanoate and hexanoate on myocardial citric acid cycle intermediates following ischemia-reperfusion
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.
Similar articles
-
Differential effects of octanoate and heptanoate on myocardial metabolism during extracorporeal membrane oxygenation in an infant swine model.Am J Physiol Heart Circ Physiol. 2015 Oct;309(7):H1157-65. doi: 10.1152/ajpheart.00298.2015. Epub 2015 Jul 31. Am J Physiol Heart Circ Physiol. 2015. PMID: 26232235 Free PMC article.
-
Dipropionylcysteine ethyl ester compensates for loss of citric acid cycle intermediates during post ischemia reperfusion in the pig heart.Cardiovasc Drugs Ther. 2009 Dec;23(6):459-69. doi: 10.1007/s10557-009-6208-1. Cardiovasc Drugs Ther. 2009. PMID: 19967553 Free PMC article.
-
Effects of exercise training on contractile function in myocardial trabeculae after ischemia-reperfusion.J Appl Physiol (1985). 2005 Jul;99(1):230-6. doi: 10.1152/japplphysiol.00850.2004. Epub 2005 Mar 17. J Appl Physiol (1985). 2005. PMID: 15774705
-
Hibernating myocardium: a review.J Mol Cell Cardiol. 1996 Dec;28(12):2359-72. doi: 10.1006/jmcc.1996.0229. J Mol Cell Cardiol. 1996. PMID: 9004153 Review.
-
Time course and mechanisms of contractile dysfunction during acute myocardial ischemia.Circulation. 1993 May;87(5 Suppl):IV35-42. Circulation. 1993. PMID: 8485832 Review.
Cited by
-
Cardiac anaplerosis in health and disease: food for thought.Cardiovasc Res. 2011 May 1;90(2):210-9. doi: 10.1093/cvr/cvr055. Epub 2011 Mar 11. Cardiovasc Res. 2011. PMID: 21398307 Free PMC article. Review.
-
Pyruvate modifies metabolic flux and nutrient sensing during extracorporeal membrane oxygenation in an immature swine model.Am J Physiol Heart Circ Physiol. 2015 Jul 1;309(1):H137-46. doi: 10.1152/ajpheart.00011.2015. Epub 2015 Apr 24. Am J Physiol Heart Circ Physiol. 2015. PMID: 25910802 Free PMC article.
-
Superior cardiac function via anaplerotic pyruvate in the immature swine heart after cardiopulmonary bypass and reperfusion.Am J Physiol Heart Circ Physiol. 2008 Dec;295(6):H2315-20. doi: 10.1152/ajpheart.00739.2008. Epub 2008 Oct 10. Am J Physiol Heart Circ Physiol. 2008. PMID: 18849332 Free PMC article.
-
Differential effects of octanoate and heptanoate on myocardial metabolism during extracorporeal membrane oxygenation in an infant swine model.Am J Physiol Heart Circ Physiol. 2015 Oct;309(7):H1157-65. doi: 10.1152/ajpheart.00298.2015. Epub 2015 Jul 31. Am J Physiol Heart Circ Physiol. 2015. PMID: 26232235 Free PMC article.
-
Triiodothyronine facilitates weaning from extracorporeal membrane oxygenation by improved mitochondrial substrate utilization.J Am Heart Assoc. 2014 Mar 20;3(2):e000680. doi: 10.1161/JAHA.113.000680. J Am Heart Assoc. 2014. PMID: 24650924 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
