This review highlights the changes in fatty acid homeostasis in the postischemic heart. The impact of restoration of flow (reperfusion) after an ischemic episode on both structural fatty acids (ie, incorporated in phospholipids, the building blocks of cellular membranes) and fatty acids, serving as energy donors by mitochondrial oxidation, are discussed. Attempts to interfere with cardiac fatty acid homeostasis to prevent loss of cardiac function or to restore cardiac performance after reperfusion is also discussed.
Van der Vusse GJ, Glatz JF, Stam HC, Reneman RS. Fatty acid homeostasis in the normoxic and ischemic heart. Physiol Rev.1992;72:881-940.
2.
van Bilsen M, van der Vusse GJ, Gilde AJ, Lindhout M, van der Lee KA. Peroxisome proliferator-activated receptors: lipid binding proteins controling gene expression. Mol Cell Biochem. 2002;239:131-138.
3.
Ford DA. Alterations in myocardial lipid metabolism during myocardial ischemia and reperfusion. Progr Lipid Res. 2002;41:6-26.
4.
Van der Vusse GJ, Reneman RS, Van Bilsen M.Accumulation of arachidonic acid in ischemic/reperfused cardiac tissue: possible causes and consequences. Prostaglandins Leukot Essent Fatty Acids. 1997;57:85-93.
5.
Weglicki WB, Owens K, Urschel CW, Serur JR, Sonnenblick EH. Hydrolysis of myocardial lipids during acidosis and ischemia. Recent Adv Stud Cardiac Struct Metab. 1973;3:781-793.
6.
Van der Vusse GJ, Roemen TH, Prinzen FW, Coumans WA, Reneman RS. Uptake and tissue content of fatty acids in dog myocardium under normoxic and ischemic conditions. Circ Res. 1982;50:538-546.
7.
Chien KR, Han A, Sen A, Buja LM, Willerson JT. Accumulation of unesterified arachidonic acid in ischemic canine myocardium. Relationship to a phosphatidylcholine deacylation-reacylation cycle and the depletion of membrane phospholipids. Circ Res. 1984;54:313-322.
8.
Van Bilsen M, Van der Vusse GJ, Willemsen PH, Coumans WA, Roemen TH, Reneman RS. Lipid alterations in isolated, working rat hearts during ischemia and reperfusion: its relation to myocardial damage. Circ Res. 1989;64:304-314.
9.
Asemu G, Dent MR, Singal T, Dhalla NS, Tappia PS. Differential changes in phospholipase D and phosphatidate phosphohydrolase activities in ischemiareperfusion of rat heart. Arch Biochem Biophys. 2005; 436:1-1.
Van der Vusse GJ, Van Bilsen M, Glatz JF, et al. Critical steps in cellular fatty acid uptake and utilization. Mol Cell Biochem. 2002;239:9-15.
12.
Glatz JF, Van Nieuwenhoven FA, Luiken JJ, Schaap FG, van der Vusse GJ. Role of membrane-associated and cytoplasmic fatty acid-binding proteins in cellular fatty acid metabolism. Prostaglandins Leukot Essent Fatty Acids. 1997;57:373-378.
13.
Kantor PF, Dyck JR, Lopaschuk GD. Fatty acid oxidation in the reperfused ischemic heart. Am J Med Sci. 1999;318:3-14.
14.
Lerch R. Oxidative substrate metabolism during postischemic reperfusion. Basic Res Cardiol. 1993;88:525-544.
15.
Aasum E, Hafstad AD, Larsen TS. Changes in substrate metabolism in isolated mouse hearts following ischemiareperfusion. Mol Cell Biochem. 2003;249:97-103.
16.
Lopaschuk GD, Wambolt RB, Barr RL. An imbalance between glycolysis and glucose oxidation is a possible explanation for the detrimental effect of high levels of fatty acids during aerobic reperfusion of ischemic hearts. J Pharmacol Exp Ther. 1993;264:135-144.
17.
Demaison L, Grynberg A.Cellular and mitochondrial energy metabolism in the stunned myocardium. Basic Res Cardiol. 1994;89:293-307.
18.
Lopaschuk GD. Alterations in fatty acid oxidation during reperfusion of the heart after myocardial ischemia. Am J Cardiol. 1997;80:11A-16A.
19.
Kudo N, Barr AJ, Barr RL, et al. High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5'-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. J Biol Chem. 1995;270:17513-17520.
20.
Hopkins TA, Dyck JR, Lopaschuk GD. AMP-activated protein kinase regulation of fatty acid oxidation in the ischemic heart. Biochem Soc Trans. 2003;31:207-212.
21.
Tamm C, Benzi R, Papageorgiou I, Tardy I, Lerch R.Substrate competition in postischemic myocardium. Effect of substrate availability during reperfusion on metabolic and contractile recovery in isolated rat hearts. Circ Res. 1994;75:1103-1112.
22.
Hacker TA, Renstrom B, Nellis SH, Liedtke AJ. Effect of repetitive stunning on myocardial metabolism in pig hearts. Am J Physiol. 1997;273:H1395-H1402.
23.
Solomon MA, Jeffrey FM, Storey CJ, Sherry AD, Malloy CR. Substrate selection early after reperfusion of ischemic regions in the working rabbit heart. Magn Reson Med. 1996;35:820-826.
24.
Pietersen HG, Langenberg CJ, Geskes G, et al. Myocardial substrate and oxidation during and after routine cardiac surgery. J Thorac Cardiovasc Surg. 1999;118:71-80.
25.
Sakamoto T, Aoki M, Imai Y, Nemoto S.Carnitine affects fatty acid metabolism after cardioplegic arrest in neonatal rabbit hearts. Ann Thorac Surg. 2001;71:648-653.
26.
Van de Velde M, Wouters PF, Rolf N, Van Aken H, Flameng W, Vandermeersch E.Long-chain triglycerides improve recovery from myocardial stunning in conscious dogs. Cardiovasc Res. 1996;32:1008-1015.
27.
Zacharowski K, Blackburn B, Thiemermann C.Ranolazine, a partial fatty acid oxidation inhibitor, reduces myocardial infarct size and cardiac troponin T release in the rat. Eur J Pharmacol. 2001;418:105-110.
28.
Marzilli M.Cardioprotective effects of trimetazidine: a review. Curr Med Res Opin. 2003;19:661-672.
29.
Stanley WC, Lopaschuk GD, Hall JL, et al. Regulation of myocardial carbohydrate metabolism under normal and ischemic conditions. Potential for pharmacological interventions. Cardiovasc Res. 1997;33:243-257.
30.
Opie LH, Sack MN. Metabolic plasticity and the promotion of cardiac protection in ischema and ischemic preconditioning. J Mol Cell Cardiol. 2002;34:1077-1089.
31.
Broderick TL, Quinney HA, Barker CC, Lopaschuk GD. Beneficial effect of carnitine on mechanical recovery of rat hearts reperfused after a transient period of local ischemia is accompanied by a stimulation of glucose oxidation. Circulation. 1993;87:972-981.
32.
Yue TL, Bao W, Jucker BM, et al. Activation of peroxisome proliferator-activated receptor-alpha protects the heart from ischemia/reperfusion injury. Circulation. 2003;108: 2393-2399.
