Impaired energetics in heart failure - A new therapeutic target

Pharmacology and Therapeutics

Volumn 119, Issue 3, 2008, Pages 264-274

  Ormerod, Julian O M ^a   Ashrafian, Houman ^b   Frenneaux, Michael P ^a  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Heart failure; Metabolic agents; Myocardial energetics

Indexed keywords

ACETYL COENZYME A ACYLTRANSFERASE; ACETYL COENZYME A ACYLTRANSFERASE INHIBITOR; ACIPIMOX; ADENOSINE TRIPHOSPHATE; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BIGUANIDE DERIVATIVE; BUCINDOLOL; DICHLOROACETIC ACID; ENZYME INHIBITOR; ETOMOXIR; FENOFIBRATE; FIBRIC ACID DERIVATIVE; GEMFIBROZIL; GLITAZONE DERIVATIVE; GLUCOSE; INSULIN; LIPOPROTEIN LIPASE; LIPOPROTEIN LIPASE INHIBITOR; METOPROLOL; NEBIVOLOL; NICOTINIC ACID; OXFENICINE; PERHEXILINE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PLACEBO; PYRUVATE DEHYDROGENASE; PYRUVIC ACID; RANOLAZINE; TRIMETAZIDINE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AMINOTRANSFERASE BLOOD LEVEL; CLINICAL TRIAL; DISEASE MODEL; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG DOSE TITRATION; DRUG EFFECT; DRUG MECHANISM; ENERGY TRANSFER; ENZYME ACTIVITY; ENZYME INHIBITION; FATTY ACID OXIDATION; FLUID RETENTION; GLYCOLYSIS; HEART FAILURE; HEART MITOCHONDRION; HEART MUSCLE METABOLISM; HUMAN; LIPID STORAGE; LIVER FAILURE; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REACTION ANALYSIS; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; WEIGHT GAIN;

ANIMALS; CARBOHYDRATE METABOLISM; ENERGY METABOLISM; HEART FAILURE; HUMANS; MODELS, BIOLOGICAL; MYOCARDIUM; OXIDATION-REDUCTION;

EID: 50549094715     PISSN: 01637258     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2008.05.007     Document Type: Review

References (174)

1. Abel E.D., Kaulbach H.C., Tian R., Hopkins J.C.A., Duffy J., Doetschman T., Minnemann T., Boers M.E., Hadro E., Oberste-Berghaus C., Quist W., Lowell B.B., Ingwall J.S., and Kahn B.B. Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart. J Clin Invest 104 (1999) 1703-1714
2. Allard M.F. Energy substrate metabolism in cardiac hypertrophy. Curr Hypertens Rep 6 (2004) 430-435
3. Alonso-Martinez J.L., Llorente-Diez B., Echegaray-Agara M., Olaz-Preciado F., Urbieta-Echezarreta M., and Gonzalez-Arencibia C. C-reactive protein as a predictor of improvement and readmission in heart failure. Eur J Heart Fail 4 (2002) 331-336
4. Amat di San F.C., Taylor M.R., Mestroni L., Botto L.D., and Longo N. Cardiomyopathy and carnitine deficiency. Mol Genet Metab (2008)
5. Asakawa M., Takano H., Nagai T., Uozumi H., Hasegawa H., Kubota N., Saito T., Masuda Y., Kadowaki T., and Komuro I. Peroxisome proliferator-activated receptor gamma plays a critical role in inhibition of cardiac hypertrophy in vitro and in vivo. Circulation 105 (2002) 1240-1246
6. Ashrafian H., Frenneaux M.P., and Opie L.H. Metabolic mechanisms in heart failure. Circulation 116 (2007) 434-448
7. Ashrafian H., Horowitz J.D., and Frenneaux M.P. Perhexiline. Cardiovasc Drug Rev 25 (2007) 76-97
8. Bank W.J., DiMauro S., Bonilla E., Capuzzi D.M., and Rowland L.P. A disorder of muscle lipid metabolism and myoglobinuria. Absence of carnitine palmityl transferase. N Engl J Med 292 (1975) 443-449
9. Barnes K., Ingram J.C., Porras O.H., Barros L.F., Hudson E.R., Fryer L.G., Foufelle F., Carling D., Hardie D.G., and Baldwin S.A. Activation of GLUT1 by metabolic and osmotic stress: Potential involvement of AMP-Activated Protein Kinase (AMPK). J Cell Sci 115 (2002) 2433-2442
10. Belardinelli L., Shryock J.C., and Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: Effects of the late sodium current inhibitor ranolazine. Heart 92 (2006) 6-14
11. Belardinelli R., and Purcaro A. Effects of trimetazidine on the contractile response of chronically dysfunctional myocardium to low-dose dobutamine in ischaemic cardiomyopathy. Eur Heart J 22 (2001) 2164-2170
12. Belardinelli R., Solenghi M., Volpe L., and Purcaro A. trimetazidine improves endothelial dysfunction in chronic heart failure: An antioxidant effect. Eur Heart J 28 (2007) 1102-1108
13. Berger J., and Moller D.E. The mechanisms of action of PPARs. Annu Rev Med 53 (2002) 409-435
14. Bersin R.M., Wolfe C., Kwasman M., Lau D., Klinski C., Tanaka K., Khorrami P., Henderson G.N., Demarco T., and Chatterjee K. Improved hemodynamic function and mechanical efficiency in congestive-heart-failure with sodium dichloroacetate. J Am Coll Cardiol 23 (1994) 1617-1624
15. Bielefeld D.R., Vary T.C., and Neely J.R. Inhibition of carnitine palmitoyl-CoA transferase activity and fatty acid oxidation by lactate and oxfenicine in cardiac muscle. J Mol Cell Cardiol 17 (1985) 619-625
16. Bittl J.A., and Ingwall J.S. Intracellular high-energy phosphate transfer in normal and hypertrophied myocardium. Circulation 75 (1987) 96-101
17. Boehm E.A., Jones B.E., Radda G.K., Veech R.L., and Clarke K. Increased Uncoupling proteins and decreased efficiency in palmitate-perfused hyperthyroid rat heart. Am J Physiol, Heart Circ Physiol 280 (2001) H977-H983
18. Bogacka I., Ukropcova B., McNeil M., Gimble J.M., and Smith S.R. Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro. J Clin Endocrinol Metab 90 (2005) 6650-6656
19. Bolukoglu H., Goodwin G.W., Guthrie P.H., Carmical S.G., Chen T.M., and Taegtmeyer H. Metabolic fate of glucose in reversible low-flow ischemia of the isolated working rat heart. Am J Physiol, Heart Circ Physiol 39 (1996) H817-H826
20. Bonello L., Sbragia P., Amabile N., Com O., Pierre S.V., Levy S., and Paganelli F. Protective effect of an acute oral loading dose of trimetazidine on myocardial injury following percutaneous coronary intervention. Heart 93 (2007) 703-707
21. Botker H.E., Helligso P., Kimose H.H., Thomassen A.R., and Nielsen T.T. Determination of high-energy phosphates and glycogen in cardiac and skeletal-muscle biopsies, with special reference to influence of biopsy technique and delayed freezing. Cardiovasc Res 28 (1994) 524-527
22. Brand M.D., Affourtit C., Esteves T.C., Green K., Lambert A.J., Miwa S., Pakay J.L., and Parker N. Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Radic Biol Med 37 (2004) 755-767
23. Braunwald E., and Bristow M.R. Congestive heart failure: Fifty years of progress. Circulation 102 (2000) 14-23
24. Bristow M. Etomoxir: A new approach to treatment of chronic heart failure. Lancet 356 (2000) 1621-1622
25. Brunmair B., Staniek K., Gras F., Scharf N., Althaym A., Clara R., Roden M., Gnaiger E., Nohl H., Waldhausl W., and Furnsinn C. Thiazolidinediones, like metformin, inhibit respiratory complex I: A common mechanism contributing to their antidiabetic actions?. Diabetes 53 (2004) 1052-1059
26. Ceolotto G., Gallo A., Papparella I., Franco L., Murphy E., Iori E., Pagnin E., Fadini G.P., Albiero M., Semplicini A., and Avogaro A. Rosiglitazone reduces glucose-induced oxidative stress mediated by NAD(P)H oxidase via AMPK-dependent mechanism. Arterioscler Thromb Vasc Biol 27 (2007) 2627-2633
27. Chaitman B.R., Pepine C.J., Parker J.O., Skopal J., Chumakova G., Kuch J., Wang W.D., Skettino S.L., and Wolff A.A. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina - A randomized controlled trial. Jama-J Ame Med Assoc 291 (2004) 309-316
28. Chandler M.P., Kerner J., Huang H., Vazquez E., Reszko A., Martini W.Z., Hoppel C.L., Imai M., Rastogi S., Sabbah H.N., and Stanley W.C. Moderate severity heart failure does not involve a downregulation of myocardial fatty acid oxidation. Am J Physiol, Heart Circ Physiol 287 (2004) H1538-H1543
29. Ciapponi A., Pizarro R., and Harrison J. Trimetazidine for Stable Angina. Cochrane Database Syst Rev 19 (2005) CD003614
30. Clarke B., Wyatt K.M., and McCormack J.G. Ranolazine increases active pyruvate dehydrogenase in perfused normoxic rat hearts: evidence for an indirect mechanism. J Mol Cell Cardiol 28 (1996) 341-350
31. Cohn J.N., Pfeffer M.A., Rouleau J., Sharpe N., Swedberg K., Straub M., Wiltse C., and Wright T.J. Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail 5 (2003) 659-667
32. Cole P.L., Beamer A.D., Mcgowan N., Cantillon C.O., Benfell K., Kelly R.A., Hartley L.H., Smith T.W., and Antman E.M. Efficacy and safety of perhexiline-maleate in refractory angina - A double-blind placebo-controlled clinical-trial of a novel antianginal agent. Circulation 81 (1990) 1260-1270
33. Coleman G.M., Gradinac S., Taegtmeyer H., Sweeney M., and Frazier O.H. Efficacy of metabolic support with glucose-insulin-potassium for left ventricular pump failure after aortocoronary bypass surgery. Circulation 80 (1989) I91-I96
34. Corton J.M., Gillespie J.G., Hawley S.A., and Hardie D.G. 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating amp-activated protein kinase in intact cells?. Eur J Biochem 229 (1995) 558-565
35. Cottin Y., Lhuillier I., Gilson L., Zeller M., Bonnet C., Toulouse C., Louis P., Rochette L., Girard C., and Wolf J.E. glucose insulin potassium infusion improves systolic function in patients with chronic ischemic cardiomyopathy. Eur J Heart Fail 4 (2002) 181-184
36. Davila-Roman V.G., Vedala G., Herrero P., las Fuentes L., Rogers J.G., Kelly D.P., and Gropler R.J. Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy. J Am Coll Cardiol 40 (2002) 271-277
37. 2+-ATPase - Regulation by ADP. J Biol Chem 276 (2001) 25078-25087
38. Denton R.M., and McCormack J.G. On the role of the calcium-transport cycle in heart and other mammalian mitochondria. Febs Lett 119 (1980) 1-8
39. Di Napoli P., Di Giovanni P., Gaeta M.A., D'Apolito G., and Barsotti A. Beneficial effects of trimetazidine treatment on exercise tolerance and b-type natriuretic peptide and troponin t plasma levels in patients with stable ischemic cardiomyopathy. Am Heart J 154 (2007)
40. Di Napoli P., Di Giovanni P., Gaeta M.A., Taccardi A.A., and Barsotti A. Trimetazidine and reduction in mortality and hospitalization in patients with ischemic dilated cardiomyopathy: a post hoc analysis of the Villa Pini D'Abruzzo trimetazidine trial. J Cardiovasc Pharmacol 50 (2007) 585-589
41. Di Napoli P., Taccardi A.A., and Barsotti A. Long term cardioprotective action of trimetazidine and potential effect on the inflammatory process in patients with ischaemic dilated cardiomyopathy. Heart 91 (2005) 161-165
42. Diaz R., Goyal A., Mehta S.R., Afzal R., Xavier D., Pais P., Chrolavicius S., Zhu J., Kazmi K., Liu L., Budaj A., Zubaid M., Avezum A., Ruda M., and Yusuf S. Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction. JAMA 298 (2007) 2399-2405
43. Dobbins R.L., Szczepaniak L.S., Bentley B., Esser V., Myhill J., and McGarry J.D. Prolonged inhibition of muscle carnitine palmitoyltransferase-1 promotes intramyocellular lipid accumulation and insulin resistance in rats. Diabetes 50 (2001) 123-130
44. Dorner A., and Schultheiss H.P. The myocardial expression of the adenine nucleotide translocator isoforms is specifically altered in dilated cardiomyopathy. Herz 25 (2000) 176-180
45. Drake-Holland A.J., and Passingham J.E. The effect of oxfenicine on cardiac carbohydrate metabolism in intact dogs. Basic Res Cardiol 78 (1983) 19-27
46. Duan S.Z., Ivashchenko C.Y., Russell M.W., Milstone D.S., and Mortensen R.M. Cardiomyocyte-specific knockout and agonist of peroxisome proliferator-activated receptor-gamma both induce cardiac hypertrophy in mice. Circ Res 97 (2005) 372-379
47. Echtay K.S., Roussel D., St Pierre J., Jekabsons M.B., Cadenas S., Stuart J.A., Harper J.A., Roebuck S.J., Morrison A., Pickering S., Clapham J.C., and Brand M.D. Superoxide activates mitochondrial uncoupling proteins. Nature 415 (2002) 96-99
48. Eichhorn E.J., Bedotto J.B., Malloy C.R., Hatfield B.A., Deitchman D., Brown M., Willard J.E., and Grayburn P.A. Effect of beta-adrenergic-blockade on myocardial-function and energetics in congestive heart-failure - Improvements in hemodynamic, contractile, and diastolic performance with bucindolol. Circulation 82 (1990) 473-483
49. Eichhorn E.J., Heesch C.M., Barnett J.H., Alvarez L.G., Fass S.M., Grayburn P.A., Hatfield B.A., Marcoux L.G., and Malloy C.R. Effect of metoprolol on myocardial-function and energetics in patients with nonischemic dilated cardiomyopathy - A randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 24 (1994) 1310-1320
50. El Mir M.Y., Nogueira V., Fontaine E., Averet N., Rigoulet M., and Leverve X. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem 275 (2000) 223-228
51. Eurich D.T., Majumdar S.R., McAlister F.A., Tsuyuki R.T., and Johnson J.A. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure. Diabetes Care 28 (2005) 2345-2351
52. Fath-Ordoubadi F., and Beatt K.J. Glucose-insulin-potassium therapy for treatment of acute myocardial infarction: an overview of randomized placebo-controlled trials. Circulation 96 (1997) 1152-1156
53. Fediuc S., Pimenta A.S., Gaidhu M.P., and Ceddia R.B. Activation of AMP-activated protein kinase, inhibition of pyruvate dehydrogenase activity, and redistribution of substrate partitioning mediate the acute insulin-sensitizing effects of troglitazone in skeletal muscle cells. J Cell Physiol 215 (2008) 392-400
54. Finck B.N., and Kelly D.P. PGC-1 coactivators: Inducible regulators of energy metabolism in health and disease. J Clin Invest 116 (2006) 615-622
55. Fiordaliso F., Leri A., Cesselli D., Limana F., Safai B., Nadal-Ginard B., Anversa P., and Kajstura J. Hyperglycemia activates P53 and P53-regulated genes leading to myocyte cell death. Diabetes 50 (2001) 2363-2375
56. Fragasso G., Palloshi A., Puccetti P., Silipigni C., Rossodivita A., Pala M., Calori G., Alfieri O., and Margonato A. A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation inhibitor, in patients with heart failure. J Am Coll Cardiol 48 (2006) 992-998
57. Fragasso G., Perseghin G., De Cobelli F., Esposito A., Palloshi A., Lattuada G., Scifo P., Calori G., Del Maschio A., and Margonato A. Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure. Eur Heart J 27 (2006) 942-948
58. Fraser H., Belardinelli L., Wang L., Light P.E., McVeigh J.J., and Clanachan A.S. Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol 41 (2006) 1031-1038
59. Frick M.H., Elo O., Haapa K., Heinonen O.P., Heinsalmi P., Helo P., Huttunen J.K., Kaitaniemi P., Koskinen P., Manninen V., Maenpaa H., Malkonen M., Manttari M., Norola S., Pasternack A., Pikkarainen J., Romo M., Sjoblom T., and Nikkila E.A. Helsinki Heart-Study - primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia - safety of treatment, changes in risk-factors, and incidence of coronary heart-disease. N Engl J Med 317 (1987) 1237-1245
60. Garnier A., Fortin D., Delomenie C., Momken I., Veksler V., and Ventura-Clapier R. Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol (Lond) 551 (2003) 491-501
61. Gertz E.W., Wisneski J.A., Stanley W.C., and Neese R.A. Myocardial substrate utilization during exercise in humans - Dual carbon-labeled carbohydrate isotope experiments. J Clin Invest 82 (1988) 2017-2025
62. Gilde A.J., van der Lee K.A.J.M., Willemsen P.H.M., Chinetti G., van der Leij F.R., van der Vusse G.J., Staels B., and van Bilsen M. Peroxisome Proliferator-Activated Receptor (PPAR) Alpha and PPAR Beta/Delta, but Not PPAR Gamma, modulate the expression of genes involved in cardiac lipid metabolism. Circ Res 92 (2003) 518-524
63. Gradinac S., Coleman G.M., Taegtmeyer H., Sweeney M.S., and Frazier O.H. Improved cardiac function with glucose-insulin-potassium after aortocoronary bypass grafting. Ann Thorac Surg 48 (1989) 484-489
64. Griffin J.L., White L.T., and Lewandowski E.D. Substrate-dependent proton load and recovery of stunned hearts during pyruvate dehydrogenase stimulation. Am J Physiol, Heart Circ Physiol 279 (2000) H361-H367
65. Haim M., Benderly M., Brunner D., Behar S., Graff E., Reicher-Reiss H., and Goldbourt U. Elevated serum triglyceride levels and long-term mortality in patients with coronary heart disease: the bezafibrate infarction prevention (BIP) registry. Circulation 100 (1999) 475-482
66. Hansford R.G., and Cohen L. Relative importance of pyruvate dehydrogenase interconversion and feed-back inhibition in the effect of fatty acids on pyruvate oxidation by rat heart mitochondria. Arch Biochem Biophys 191 (1978) 65-81
67. 2+ cycling in isolated failing human myocardium. Circulation 105 (2002) 194-199
68. Hayashida W., van Eyll C., Rousseau M.F., and Pouleur H. Effects of ranolazine on left ventricular regional diastolic function in patients with ischemic heart disease. Cardiovasc Drugs Ther 8 (1994) 741-747
69. Hermann H.P., Pieske B., Schwarzmuller E., Keul J., Just H., and Hasenfuss G. Haemodynamic effects of intracoronary pyruvate in patients with congestive heart failure: an open study. Lancet 353 (1999) 1321-1323
70. Hjalmarson A., Goldstein S., Fagerberg B., Wedel H., Waagstein F., Kjekshus J., Wikstrand J., Westergren G., Hassle A., Thimell M., El Allaf D., Vitovec J., Aldershvile J., Halinen M., Dietz R., Neuhaus K.L., Janosi A., Thorgeirsson G., Dunselman P., Gullestad L., Kuch J., Herlitz J., Rickenbacher P., Ball S., Gottlieb S., Deedwania P., Vandenhoven G., Novakova I., Danker S., Lundstrom M., Meyer-Sabellek W., Balla I., Sveinsdottir M., Dorhout B., Hildebrandt A., Szczurko I., Larsson C., Bucher E., Scott E., Dwyer D., Julian D.G., Demets D.L., Chatterjee K., Feyzi J., Lehto S., Karpati P., Motz W., Samuelsson O., Viersma J.W., Andersson B., Berthe C., Boutefeu J.M., Boxho G., Decroly P., Derbaudrenghien J.P., El Allaf D., Pirlet J., Henry P., Heyndrickx G., Missault L., Nannan M., Timmermans P., Vachiery J.L., Van Mieghem W., Vandenbossche J.L., Dvorak K., Herold M., Hradec J., Kana A., Petr P., Rybka J., Smid J., Svitil P., Toman J., Vitovec J., Agner E., Aldershvile J., Amtorp O., Egstrup K., Eliasen P., Gotzsche C.O., Hildebrandt P., Johannesen A., Kaiser-Nielsen P., Nielsen H., Nielsen P.E., Pedersen F., Nielsen J.R., Skagen K., Halinen M., Honkanen T., Hussi E., Juvonen J., Jaaskelainen H., Rinne J., Salonen T., Andresen D., Berwing H., Dietz R., Forster A., Hauf G.F., Krosse B., Luderitz B., von Olshausen K.E., Schmailzl K.J.G., Schwimmbeck P.L., Sigmund M., Voller H., Czuriga I., Hetey M., Janosi A., Katona A., Lengyel M., Nyaradi A., Rednik A., Sandori K., Szabo P., Tarjan J., Tenczer J., Timar S., Valyi P., Veress G., Zamolyi K., Oze B., Thorgeirsson G., Thorgeirsson G., Bernink P.J.L.M., Bredero A.C., Breedveld R.W., Breuls P.N.W.M., Bucx J.J.J., Cornel J.H., De Milliano P.A.R., Dunselman P.H.J.M., Hamer B.J.B., Holwerda N.L., Hoogsteen J., Hoorntje J.C.A., Kragten J.A., Liem A.H., Linssen G.C., Michels H.R., Misier A.R.R., Schaafsma H.J., Sijbring P., Taverne R.J.T., Van Kempen L.H.J., Van Stralen R., Van Veldhuisen D.J., Veerhoek M.J., Werter C.J.P.J., Wesdorp J.C., Willems A.R., Withagen A.J.A., Zwart P.A.G., Bjornerheim R., Dahle M., Dickstein K., Froland G.S., Gullestad L., Gundersen T., Hofsoy K., Hole T.L., Johansen T., Mannsverk J., Nesje P., Omland T.M., Sjodin C., Smith P., Tjonndal H.A., Vikesdal O., Waage K., Jaworska K., Kolodziej P., Kornacewicz-Jach Z., Krzeminska-Pakula M., Kuch J., Piotrowski J.W., Piwowarska W., Stogowski A., Wodniecki J., Wrabec K., Ahlstrom P., Ekdahl S., Hemmingson L.O., Herlitz J., Holmberg L., Lernfelt B., Nilsson H., Widgren B., Angman K., Erne P., Mohacsi P., Polikar R., Rickenbacher P., Schlapfer H., Batin P., Berkin K.E., Callaghan T.S., Forfar J., Frenneaux M., Greenbaum R.A., Maltz M., Murdoch D., Reynolds G., Stephens J., Struthers A., Swan J., Tildesley G., Abbasi A., Alagona P., Alderman J., Alipour M., Anderson J.L., Ansari Z., Ashraf M., Beanblossom B.T., Bennett S., Benvenuti D., Berk M.R., Bhalla R., Bilazarian S.D., Browne K.F., Buchter C.M., Carlson R., Carlson C.J., Danisa K., Dauber I., Dewood M.A., Deedwania P., Dennish G., Denny D.M., DiBianco R., Diller P.M., Dunlap M., Dowd K., Edmiston A., El Shahawy M., Elkayam U., Farnham J., Fenster P., Friedman S., Heywood T., Galichia J.P., Geller M., Ghali J.K., Gheorghiade M., Giles T., Gillespe R., Goldberg G., Goldberg M.C., Goldscher D.A., Gooden G.P., Goodman M., and Goodman L. Effect of metoprolol CR XL in chronic heart failure: Metoprolol CR XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 353 (1999) 2001-2007
71. Holubarsch C.J.F., Rohrbach M., Karrasch M., Boehm E., Polonski L., Ponikowski P., and Rhein S. A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: The ERGO (Etomoxir for the Recovery of Glucose Oxidation) Study. Clin Sci 113 (2007) 205-212
72. Hood D.A. Plasticity in skeletal, cardiac, and smooth muscle. Contractile activity-induced mitochondrial biogenesis in skeletal muscle. J Appl Physiol 90 (2001) 1137-1157
73. 2+ release be developed using mouse models?. Circ Res 96 (2005) 1031-1032
74. Hultman E. Pyruvate dehydrogenase as a regulator of substrate utilization in skeletal muscle. In: Maughan R.J., and Shirreffs S.M. (Eds). Biochemistry of Exercise IX (1996), Human Kinetics, Champaign, IL Ref Type: Serial (Book,Monograph)
75. Hutter J.F., Piper H.M., and Spieckermann P.G. Effect of fatty-acid oxidation on efficiency of energy-production in rat-heart. Am J Physiol 249 (1985) H723-H728
76. Ide T., Tsutsui H., Hayashidani S., Kang D.C., Suematsu N., Nakamura K., Utsumi H., Hamasaki N., and Takeshita A. Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res 88 (2001) 529-535
77. Jackson G. Ranolazine - a nicely timed new medical therapy for stable angina. Int J Clin Pract 61 (2007) 1063
78. Jessup M., and Brozena S. Medical progress: Heart failure. N Engl J Med 348 (2003) 2007-2018
79. Katz A.M. Heart Failure: Pathophysiology, Molecular Biology and Clinical Management (2000), Lippincott Williams & Wilkins, Philadelphia
80. Kerbey A.L., Randle P.J., Cooper R.H., Whitehouse S., Pask H.T., and Denton R.M. Regulation of pyruvate dehydrogenase in rat heart. mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: Role of coenzyme A, acetyl-coenzyme A and reduced and oxidized nicotinamide-adenine dinucleotide. Biochem J 154 (1976) 327-348
81. Kjekshus J.K., and Mjos O.D. Effect of free fatty-acids on myocardial function and metabolism in ischemic dog heart. J Clin Invest 51 (1972) 1767
82. Knuuti M.J., Maki M., Ykijarvinen H., Voipiopulkki L.M., Harkonen R., Haaparanta M., and Nuutila P. The effect of insulin and Ffa on myocardial glucose-uptake. J Mol Cell Cardiol 27 (1995) 1359-1367
83. Kurth-Kraczek E.J., Hirshman M.F., Goodyear L.J., and Winder W.W. 5' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes 48 (1999) 1667-1671
84. Labrou A., Giannoglou G., Zioutas D., Fragakis N., Katsaris G., and Louridas G. Trimetazidine administration minimizes myocardial damage and improves left ventricular function after percutaneous coronary intervention. Am J Cardiovasc Drugs 7 (2007) 143-150
85. Lago R.M., Singh P.P., and Nesto R.W. Congestive heart failure and cardiovascular death in patients with prediabetes and Type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet 370 (2007) 1129-1136
86. Lambert A.J., and Brand M.D. Superoxide production by NADH:ubiquinone oxidoreductase (complex I) depends on the ph gradient across the mitochondrial inner membrane. Biochem J 382 (2004) 511-517
87. Lassers B.W., Wahlqvis M.L., Kaijser L., and Carlson L.A. Effect of nicotinic-acid on myocardial metabolism in man at rest and during exercise. J Appl Physiol 33 (1972) 72
88. Lechat P., Brunhuber K.W., Hofmann R., Kuhn P., Nesser H.J., Slany J., Weihs W., Wiedermann C., Wimmer H., Van Mieghem W., Boland J., Chaudron J.M., Jordaens L., Melchior J.P., Aschermann M., Bruthansl J., Hradec M., Kolbel F., Semrad B., Haghfelt T., Fischer-Hansen J., Goetzsche C.O., Hildebrandt P., Kassis E., Rasmussen V., Rokkedal J., Thomassen A., Groundstroem K., Uusimaa P., Le Heuzey J.Y., Aumont M.C., Aupetit J.F., Baille N., Baudouy P., Belin A., Bonneau A., Bonneric G., Bousser J.P., Citron B., Dary P., Decoulx E., De Groote P., Denolle T., Dievart F., Duriez P., Eicher J.C., Enjuto G., Ferriere M., Fournier E., Garandeau M., Gauthier J., Genest M., Gerbe A., Godenir J.P., Guillot B., Guillot J.P., Guillot P., Heno P., d'Ivernois C., Jean M., Kacet S., Kalle R., Komajda M., Lacroix A., Lallemand R., Lardoux H., Marquet M., Martin M., Martin O., Mery D., Mossaz R., Mothes P., Olive T., Ostorero M., Paganelli F., Page E., Pauly-Laubry C., Puel J., Rousseau J.F., Roux J.J., Schenowitz A., Sourdais K., Tremel F., Verdun A., Witchiz S., Wolf J.E., Hombach V., Assmann I., Beyer T., Bischoff K.O., Darius H., Ertl G., Fleck E., Forster K., Freytag F., Gleichmann U., Haasis R., Henssge R., Hey D., Hesse P., Hofs T., Keck M., Klein H., Kromer E.T., Kruls-Munch J., Luderitz B., Maisch B., Mitrovic V., Neubauer S., Osterziel K.J., Simon H., Spitzer S.G., Stohring R., Taubert G., Teichmann W., Theisen K., Wende W., Wieser H., Zotz R., Preda I., Csanady M., Cserhalmi L., Edes I., Gesztesi T., Karpati P., Simon K., Tarjan J., Fogari R., Tramarin R., Galie N., Giani P., Milanese U., Scalvini S., Scrutinio D., Sechi L.A., Tettamanti F., De Vito F., Crean P., McCann H., Mulcahy D., Sugrue D., van Hoogenhuyze D.C.A., van der Burgh P.H., Ciampricotti R., van Dantzig J.M., DenHartog F.R., Henneman J.A., van Kesteren H.A.M., Kragten J.A., Liem K.L., Limburg A., van der Linde M.R., Linssen G.C.M., Pasteuning H., Penn H.J.A.M., Van Rossum P., Schaafsma H.J., Schelling A., Sloos R., Wesdorp J.C.L., Korewicki J., Achremczyk P., Czestockowska E., Dowgird M., Dyduszynski A., Gorski J., Ilmurzynska K., Janicki K., Kornacewicz-Jach Z., Kraska T., Krzeminska-Pakula M., Kuch J., Nartowicz E., Petelenz T., Piwowarska W., Rawczynska-Englert I., Ruzyllo W., Swiatecka G., Tendera M., Wierzchowiecki M., Wodniecki J., Wojciechowoski D., Wrabec K., Wysocki H., Gomes R.S., Ceia M.F., Lousada N., Campos J.M.M., Providencia L.A., de Moura A.L.Z.C., Marejev V.J., Aronov D.M., Arutjunov G.P., Bart B.J., Basechikin S.S., Belenkov J.N., Beloussov J.B., Bokeria O.A., Charchogljan R.A., Doschytsin V., Fedorova T.A., Glezer M.G., Gorbachenkov A., Gorshkov V.A., Gospodarenko A.L., Ivashkin V.T., Ivleva A.J., Kyrichenko A.A., Lavrov A.A., Lazebnik L.B., Marynov A., Mazaev V.P., Polejev N.R., Shpektor A., Sidorenko B.A., Sobolev K.E., Starodoubtsev A.K., Storozhakhov G.I., Syrkin A.L., Zodionchenko V.S., Zvereva T.V., Murin J., Kaliska G., Rybar R., Valle V., Artaza M., Conthe P., Cruz J.M., Garcia-Moll M., Lopez-Sendon J.L., Martinez A., Monzon F., Ribas M., Roig E., Roldan I., Hoglund C., Ekdahl S., Hjelmaeus L., Lindberg K., Lofdahl P., Ulvenstam G., Warselius L., Follath F., Anghern W., Dubach P., Erne P., Gallino A., Moccetti T., Bridges A., Adgey J., Ambepitiya G., Boon N., Boyle R.M., Cowley A.J., and Cripps T. The cardiac insufficiency bisoprolol study II (CIBIS-II): A randomised trial. Lancet 353 (1999) 9-13
89. Lee L., Campbell R., Scheuermann-Freestone M., Taylor R., Gunaruwan P., Williams L., Ashrafian H., Horowitz J., Fraser A.G., Clarke K., and Frenneaux M. Metabolic modulation with perhexiline in chronic heart failure - A randomized, controlled trial of short-term use of a novel treatment. Circulation 112 (2005) 3280-3288
90. Lefebvre P., Chinetti G., Fruchart J.C., and Staels B. Sorting out the roles of PPAR alpha in energy metabolism and vascular horneostasis. J Clin Invest 116 (2006) 571-580
91. Lehman J.J., Barger P.M., Medeiros D.M., and Kelly D.P. Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 (PGC-1) regulates cardiac mitochondrial number and function. Circulation 102 (2000) 16
92. Lehman J.J., and Kelly D.P. Gene regulatory mechanisms governing energy metabolism during cardiac hypertrophic growth. Heart Fail Rev 7 (2002) 175-185
93. Lewis J.F., DaCosta M., Wargowich T., and Stacpoole P. Effects of dichloroacetate in patients with congestive heart failure. Clin Cardiol 21 (1998) 888-892
94. Liao R., Nascimben L., Friedrich J., Gwathmey J.K., and Ingwall J.S. Decreased energy reserve in an animal model of dilated cardiomyopathy. Relationship to Contractile Performance. Circ Res 78 (1996) 893-902
95. Liedtke A.J. Alterations of carbohydrate and lipid-metabolism in the acutely ischemic heart. Prog in Cardiovasc Dis 23 (1981) 321-336
96. Lionetti V., Linke A., Chandler M.P., Young M.E., Penn M.S., Gupte S., d'Agostino C., Hintze T.H., Stanley W.C., and Recchia F.A. Carnitine palmitoyl transferase-i inhibition prevents ventricular remodeling and delays decompensation in pacing-induced heart failure. Cardiovasc Res 66 (2005) 454-461
97. Lochhead P.A., Salt I.P., Walker K.S., Hardie D.G., and Sutherland C. 5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase. Diabetes 49 (2000) 896-903
98. Lopaschuk G.D., Barr R., Thomas P.D., and Dyck J.R.B. Beneficial effects of trimetazidine in ex vivo working ischemic hearts are due to a stimulation of glucose oxidation secondary to inhibition of long-chain 3-ketoacyl coenzyme A thiolase. Circ Res 93 (2003) E33-E37
99. Luptak I., Yan J., Cui L., Jain M., Liao R.L., and Tian R. Long-term effects of increased glucose entry on mouse hearts during normal aging and ischemic stress. Circulation 116 (2007) 901-909
100. MacInnes A., Fairman D.A., Binding P., Rhodes J.A., Wyatt M.J., Phelan A., Haddock P.S., and Karran E.H. The antianginal agent trimetazidine does not exert its functional benefit via inhibition of mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res 93 (2003) E26-E32
101. Marin-Garcia J., Goldenthal M.J., and Moe G.W. Mitochondrial pathology in cardiac failure. Cardiovasc Res 49 (2001) 17-26
102. Maseri A. Inflammation, atherosclerosis, and ischemic events - Exploring the hidden side of the moon. N Engl J Med 336 (1997) 1014-1016
103. Masoudi F.A., Inzucchi S.E., Wang Y.F., Havranek E.P., Foody J.M., and Krumholz H.M. Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure - An observational study. Circulation 111 (2005) 583-590
104. Mehta S.R., Yusuf S., Diaz R., Zhu J., Pais P., Xavier D., Paolasso E., Ahmed R., Xie C., Kazmi K., Tai J., Orlandini A., Pogue J., and Liu L. Effect of glucose-insulin-potassium infusion on mortality in patients with acute ST-segment elevation myocardial infarction: The CREATE-ECLA randomized controlled trial. JAMA 293 (2005) 437-446
105. Merrill G.F., Kurth E.J., Hardie D.G., and Winder W.W. AICA riboside increases AMP-Activated Protein Kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol 273 (1997) E1107-E1112
106. Mjos O.D., Kjekshus J.K., and Lekven J. Importance of free fatty-acids as a determinant of myocardial oxygen-consumption and myocardial ischemic-injury during norepinephrine infusion in dogs. J Clin Invest 53 (1974) 1290-1299
107. Modesti A., Bertolozzi L., Gamberi T., Marchetta M., Lumachi C., Coppo M., Moroni F., Toscano T., Lucchese G., Gensini G.F., and Modesti P.A. Hyperglycemia activates JAK2 signaling pathway in human failing myocytes via angiotensin II-mediated oxidative stress. Diabetes 54 (2005) 394-401
108. Morgan E.E., Young M.E., McElfresh T.A., Kung T.A., Hoit B.D., Chandler M.P., and Stanley W.C. Chronic treatment with trimetazidine reduces the upregulation of atrial natriuretic peptide in heart failure. Fundam Clin Pharmacol 20 (2006) 503-505
109. Murray A.J., Anderson R.E., Watson G.C., Radda G.K., and Clarke K. Uncoupling proteins in human heart. Lancet 364 (2004) 1786-1788
110. Nesto R.W., Bell D., Bonow R.O., Fonseca V., Grundy S.M., Horton E.S., Le Winter M., Porte D., Semenkovich C.F., Smith S., Young L.H., and Kahn R. Thiazolidinedione use, fluid retention, and congestive heart failure - a consensus statement from the American heart association and American diabetes association. Circulation 108 (2003) 2941-2948
111. Neubauer S. The failing heart-An engine out of fuel. N Engl J Med 356 (2007) 1140-1151
112. Neubauer S., Horn M., Cramer M., Harre K., Newell J.B., Peters W., Pabst T., Ertl G., Hahn D., Ingwall J.S., and Kochsiek K. Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation 96 (1997) 2190-2196
113. 2+ stimulate mitochondrial biogenesis in muscle cells. Am J Physiol Endocrinol Metab 283 (2002) E1040-E1045
114. Onay-Besikci A., Guner S., Arioglu E., Ozakca I., Ozcelikay A.T., and Altan V.M. The effects of chronic trimetazidine treatment on mechanical function and fatty acid oxidation in diabetic rat hearts. Can J Physiol Pharmacol 85 (2007) 527-535
115. Opie L.H. The Heart: Physiology and Metabolism (1991), Raven, New York
116. Osorio J.C., Stanley W.C., Linke A., Castellari M., Diep Q.N., Panchal A.R., Hintze T.H., Lopaschuk G.D., and Recchia F.A. Impaired myocardial fatty acid oxidation and reduced protein expression of retinoid X receptor-alpha in pacing-induced heart failure. Circulation 106 (2002) 606-612
117. Packer M., Bristow M.R., Cohn J.N., Colucci W.S., Fowler M.B., Gilbert E.M., and Shusterman N.H. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 334 (1996) 1349-1355
118. Panchal A.R., Stanley W.C., Kerner J., and Sabbah H.N. Beta-receptor blockade decreases carnitine palmitoyl transferase I activity in dogs with heart failure. J Card Fail 4 (1998) 121-126
119. Pocock S., Wilhelmsen L., Dickstein K., Francis G., and Wittes J. The data monitoring experience in the MOXCON trial. Eur Heart J 25 (2004) 1974-1978
120. Randle P.J. Insulin and fat metabolism. Acta Cient Venez 23 (1972) 168-171
121. Randle P.J., Denton R.M., Pask H.T., and Severson D.L. Calcium ions and the regulation of pyruvate dehydrogenase. Biochem Soc Symp (1974) 75-88
122. Roberts W.C., Black H.R., Bakris G.L., Mason R.P., Giles T.D., and Sulkes D.J. The editor's roundtable: Revisiting the role of beta blockers in hypertension. Am J Cardiol 100 (2007) 253-267
123. Rosano G.M., Vitale C., Sposato B., Mercuro G., and Fini M. Trimetazidine improves left ventricular function in diabetic patients with coronary artery disease: A double-blind placebo-controlled study. Cardiovasc Diabetol 2 (2003) 16
124. Rubins H.B., Robins S.J., Collins D., Fye C.L., Anderson J.W., Elam M.B., Faas F.H., Linares E., Schaefer E.J., Schectman G., Wilt T.J., and Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med 341 (1999) 410-418
125. Rupp H., Rupp T.P., and Maisch B. Fatty acid oxidation inhibition with PPARalpha activation (FOXIB/PPARalpha) for normalizing gene expression in heart failure?. Cardiovasc Res 66 (2005) 423-426
126. Rupp H., Zarain-Herzberg A., and Maisch B. The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure. Herz 27 (2002) 621-636
127. Sabbah H.N., Chandler M.P., Mishima T., Suzuki G., Chaudhry P., Nass O., Biesiadecki B.J., Blackburn B., Wolff A., and Stanley W.C. Ranolazine, a partial fatty acid oxidation (PFOX) inhibitor, improves left ventricular function in dogs with chronic heart failure. J Card Fail 8 (2002) 416-422
128. Sabbah H.N., Sharov V., Riddle J.M., Kono T., Lesch M., and Goldstein S. Mitochondrial abnormalities in myocardium of dogs with chronic heart failure. J Mol Cell Cardiol 24 (1992) 1333-1347
129. Sack M.N., Harrington L.S., Jonassen A.K., Mjos O.D., and Yellon D.M. Coordinate regulation of metabolic enzyme encoding genes during cardiac development and following carvedilol therapy in spontaneously hypertensive rats. Cardiovasc Drugs Ther 14 (2000) 31-39
130. Sack M.N., Rader T.A., Park S.H., Bastin J., Mccune S.A., and Kelly D.P. Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation 94 (1996) 2837-2842
131. Saeedi R., Grist M., Wambolt R.B., Bescond-Jacquet A., Lucien A., and Allard M.F. Trimetazidine normalizes postischemic function of hypertrophied rat hearts. J Pharmacol Exp Ther 314 (2005) 446-454
132. Salpeter S.R., Greyber E., Pasternak G.A., and Salpeter E.E. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus - systematic review and meta-analysis. Arch Intern Med 163 (2003) 2594-2602
133. Salt I., Celler J.W., Hawley S.A., Prescott A., Woods A., Carling D., and Hardie D.G. AMP-activated protein kinase: Greater AMP dependence, and preferential nuclear localization, of complexes containing the alpha2 isoform. Biochem J 334 Pt 1 (1998) 177-187
134. Sanders M.J., Grondin P.O., Hegarty B.D., Snowden M.A., and Carling D. Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. Biochem J 403 (2007) 139-148
135. Sano M., Izumi Y., Helenius K., Asakura M., Rossi D.J., Xie M., Taffet G., Hu L.Y., Pautler R.G., Wilson C.R., Boudina S., Abel E.D., Taegtmeyer H., Scaglia F., Graham B.H., Kralli A., Shimizu N., Tanaka H., Makela T.P., and Schneider M.D. Menage-a-Trois 1 is critical for the transcriptional function of PPAR gamma coactivator 1. Cell Metab 5 (2007) 129-142
136. Schaper J., Froede R., STHEIN, Buck A., Hashizume H., Speiser B., Friedl A., and Bleese N. Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy. Circulation 83 (1991) 504-514
137. Schmidt-Schweda S., and Holubarsch C. First clinical trial with etomoxir in patients with chronic congestive heart failure. Clin Sci 99 (2000) 27-35
138. Schrauwen P., Hoeks J., Schaart G., Kornips E., Binas B., van de Vusse G.J., van Bilsen M., Luiken J.J.F.P., Coort S.L.M., Glatz J.F.C., Saris W.H.M., and Hesselinkt M.K.C. Uncoupling protein 3 as a mitochondrial fatty acid anion exporter. Faseb J 17 (2003) 2272
139. Scirica B.M., Morrow D.A., Hod H., Murphy S.A., Belardinelli L., Hedgepeth C.M., Molhoek P., Verheugt F.W.A., Gersh B.J., Mccabe C.H., and Braunwald E. Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non-ST-segment-elevation acute coronary syndrome - thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation 116 (2007) 1647-1652
140. Sharov V.G., Goussev A., Lesch M., Goldstein S., and Sabbah H.N. Abnormal mitochondrial function in myocardium of dogs with chronic heart failure. J Mol Cell Cardiol 30 (1998) 1757-1762
141. Sharov V.G., Todor A.V., Silverman N., Goldstein S., and Sabbah H.N. Abnormal mitochondrial respiration in failed human myocardium. J Mol Cell Cardiol 32 (2000) 2361-2367
142. Shaw R.J., Lamia K.A., Vasquez D., Koo S.H., Bardeesy N., Depinho R.A., Montminy M., and Cantley L.C. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310 (2005) 1642-1646
143. Shim Y.H., Kweon T.D., Lee J.H., Nam S.B., and Kwak Y.L. Intravenous glucose-insulin-potassium during off-pump coronary artery bypass surgery does not reduce myocardial injury. Acta Anaesthesiol Scand 50 (2006) 954-961
144. Smith C.A., and Rayment I. Active site comparisons highlight structural similarities between myosin and other P-loop proteins. Biophys J 70 (1996) 1590-1602
145. Sorokina N., O'Donnell J.M., McKinney R.D., Pound K.M., Woldegiorgis G., Lanoue K.F., Ballal K., Taegtmeyer H., Buttrick P.M., and Lewandowski E.D. Recruitment of compensatory pathways to sustain oxidative flux with reduced carnitine palmitoyltransferase I activity characterizes inefficiency in energy metabolism in hypertrophied hearts. Circulation 115 (2007) 2033-2041
146. Staels B., and Fruchart J.C. Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes 54 (2005) 2460-2470
147. Stanley W.C., Recchia F.A., and Lopaschuk G.D. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85 (2005) 1093-1129
148. Steiner S., Wahl D., Mangold B.L.K., Robison R., Raymackers J., Meheus L., Anderson N.L., and Cordier A. Induction of the adipose differentiation-related protein in liver of etomoxir-treated rats. Molec Cell Biol Res Commun 218 (1996) 777-782
149. Taegtmeyer H., Golfman L., Sharma S., Razeghi P., and Van Arsdall M. Linking gene expression to function: metabolic flexibility in the normal and diseased heart. Cardiac Eng: Genes Cells Struct Function 1015 (2004) 202-213
150. Taegtmeyer H., McNulty P., and Young M.E. Adaptation and maladaptation of the heart in diabetes: Part I general concepts. Circulation 105 (2002) 1727-1733
151. + during myocardial ischemia. Am J Physiol Heart Circ Physiol 293 (2007) H3036-H3045
152. 2+ activation of heart mitochondrial oxidative phosphorylation: Role of the F-0/F-1-ATPase. Am J Physiol, Cell Physiol 278 (2000) C423-C435
153. Thrainsdottir I.S., von Bibra H., Malmberg K., and Ryden L. Effects of trimetazidine on left ventricular function in patients with type 2 diabetes and heart failure. J Cardiovasc Pharmacol 44 (2004) 101-108
154. Turcani M., and Rupp H. Modification of left ventricular hypertrophy by chronic etomoxir treatment. Br J Pharmacol 126 (1999) 501-507
155. Turner R.C., Holman R.R., Cull C.A., Stratton I.M., Matthews D.R., Frighi V., Manley S.E., Neil A., McElroy K., Wright D., Kohner E., Fox C., Hadden D., Mehta Z., Smith A., Nugent Z., Peto R., Adlel A.I., Mann J.I., Bassett P.A., Oakes S.F., Dornan T.L., Aldington S., Lipinski H., Collum R., Harrison K., MacIntyre C., Skinner S., Mortemore A., Nelson D., Cockley S., Levien S., Bodsworth L., Willox R., Biggs T., Dove S., Beattie E., Gradwell M., Staples S., Lam R., Taylor F., Leung L., Carter R.D., Brownlee S.M., Fisher K.E., Islam K., Jelfs R., Williams P.A., Williams F.A., Sutton P.J., Ayres A., Logie L.J., Lovatt C., Evans M.A., Stowell L.A., Ross I., Kennedy I.A., Croft D., Keen A.H., Rose C., Raikou M., Fletcher A.E., Bulpitt C., Battersby C., Yudkin J.S., Stevens R., Stearn M.R., Palmer S.L., Hammersley M.S., Franklin S.L., Spivey R.S., Levy J.C., Tidy C.R., Bell N.J., Steemson J., Barrow B.A., Coster R., Waring K., Nolan L., Truscott E., Walravens N., Cook L., Lampard H., Merle C., Parker P., McVittie J., Draisey I., Murchison L.E., Brunt A.H.E., Williams M.J., Pearson D.W., Petrie X.M., Lean M.E., Walmsley D., Lyall F., Christie E., Church J., Thomson E., Farrow A., Stowers J.M., Stowers M., McHardy K., Patterson N., Wright A.D., Levi N.A., Shearer A.C.I., Thompson R.J.W., Taylor G., Rayton S., Bradbury M., Glover A., Smyth-Osbourne A., Parkes C., Graham J., England P., Gyde S., Eagle C., Chakrabarti B., Smith J., Sherwell J., Oakley N.W., Whitehead M.A., Hollier G.P., Pilkington T., Simpson J., Anderson M., Martin S., Kean J., Rice B., Rolland A., Nisbet J., Kohner E.M., Dornhorst A., Doddridge M.C., Dumskyij M., Walji S., Sharp P., Sleightholm M., Vanterpool G., Frost G., Roseblade M., Elliott S., Forrester S., Foster M., Myers K., Chapman R., Hayes J.R., Henry R.W., Featherston M.S., Archbold G.P.R., Copeland M., Harper R., Richardson I., Davison H.A., Alexander L., Scarpello J.H.B., Shiers D.E., Tucker R.J., Worthington J.R.H., Angris S., Bates A., Walton J., Teasdale M., Browne J., Stanley S., Davis B.A., Strange R.C., Hadden D.R., Kennedy L., Atkinson A.B., Bell P.M., McCance D.R., Rutherford J., Culbert A.M., Hegan C., Tennet H., Webb N., Robinson I., Holmes J., Nesbitt S., Spathis A.S., Hyer S., Nanson M.E., James L.M., Tyrell J.M., Davis C., Strugnell P., Booth M., Petrie H., Clark D., Hulland S., Barron J.L., Gould B.C., Singer J., Badenoch A., McGregor M., Isenberg L., Eckert M., Alibhai K., Marriot E., Cox C., Price R., Fernandez M., Ryle A., Clarke S., Wallace G., Mehmed E., Lankester J.A., Howard E., Waite A., MacFarlane S., Greenwood R.H., Wilson J., Denholm M.J., Temple R.C., Whitfield K., Johnson F., Munroe C., Gorick S., Duckworth E., Fatman M., Rainbow S., Borthwick L., Wheatcroft D.J., Seaman R.J., Christie R.A., Wheatcroft W., Musk P., White J., McDougal S., Bond M., Raniga P., Day J.L., Doshi M.J., Wilson J.G., Howard-Williams J.R., Humphreys H., Graham A., Hicks K., Hexman S., Bayliss P., Pledger D., Newton R.W., Jung R.T., Roxburgh C., Kilgallon B., Dick L., Waugh N., Kilby S., Ellingford A., Burns J., Fox C.V., Holloway M.C., Coghill H.M., and Hein N. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352 (1998) 837-853
156. Tuunanen H., Engblom E., Naum A., Nagren K., Hesse B., Airaksinen K.E., Nuutila P., Iozzo P., Ukkonen H., Opie L.H., and Knuuti J. Free fatty acid depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart failure. Circulation 114 (2006) 2130-2137
157. Undrovinas A.I., Belardinelli L., Undrovinas N.A., and Sabbah H.N. Ranolazine improves abnormal repolarization and contraction in left ventricular myocytes of dogs with heart failure by inhibiting late sodium current. J Cardiovasc Electrophysiol 17 Suppl 1 (2006) S169-S177
158. Unger S.A., Kennedy J.A., McFadden-Lewis K., Minerds K., Murphy G.A., and Horowitz J.D. Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium. J Cardiovasc Pharmacol 46 (2005) 849-855
159. van Bilsen M., van der Vusse G.J., Gilde A.J., Lindhout M., and van der Lee K.A.J.M. Peroxisome proliferator-activated receptors: Lipid binding proteins controling gene expression. Mol Cell Biochem 239 (2002) 131-138
160. Wagner R.A., Tabibiazar R., Powers J., Bernstein D., and Quertermous T. Genome-wide expression profiling of a cardiac pressure overload model identifies major metabolic and signaling pathway responses. J Mol Cell Cardiol 37 (2004) 1159-1170
161. Wallhaus T.R., Taylor M., DeGrado T.R., Russell D.C., Stanko P., Nickles R.J., and Stone C.K. Myocardial free fatty acid and glucose use after carvedilol treatment in patients with congestive heart failure. Circulation 103 (2001) 2441-2446
162. Wang P., Fraser H., Lloyd S.G., McVeigh J.J., Belardinelli L., and Chatham J.C. A comparison between ranolazine and cvt-4325, a novel inhibitor of fatty acid oxidation, on cardiac metabolism and left ventricular function in rat isolated perfused heart during ischemia and reperfusion. J Pharmacol Exp Ther 321 (2007) 213-220
163. Weber G., Convery H.J., Lea M.A., and Stamm N.B. Feedback inhibition of key glycolytic enzymes in liver: Action of free fatty acids. Science 154 (1966) 1357-1360
164. Weiss R.G., Gerstenblith G., and Bottomley P.A. ATP Flux through creatine kinase in the normal, stressed, and failing human heart. Proc Natl Acad Sci USA 102 (2005) 808-813
165. Williams F.M., Tanda K., Kus M., and Williams T.J. Trimetazidine inhibits neutrophil accumulation after myocardial ischaemia and reperfusion in rabbits. J Cardiovasc Pharmacol 22 (1993) 828-833
166. Wisneski J.A., Gertz E.W., Neese R.A., and Mayr M. Myocardial-metabolism of free fatty-acids - Studies with C-14-labeled substrates in humans. J Clin Invest 79 (1987) 359-366
167. Wolf H.P.O. Aryl-Substituted 2-Oxirane Carboxylic Acids: a New Group of Antidiabetic Drugs (1990), Smith-Gordon, London
168. Wu Z., Puigserver P., Andersson U., Zhang C., Adelmant G., Mootha V., Troy A., Cinti S., Lowell B., Scarpulla R.C., and Spiegelman B.M. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98 (1999) 115-124
169. Young L.H., Coven D.L., and Russell R.R. Cellular and molecular regulation of cardiac glucose transport. J Nucl Cardiol 7 (2000) 267-276
170. Zarain-Herzberg A., and Rupp H. Therapeutic potential of CPT I inhibitors: cardiac gene, transcription as a target. Expert Opin Investig Drugs 11 (2002) 345-356
171. ZarainHerzberg A., Rupp H., Elimban V., and Dhalla N.S. Modification of sarcoplasmic reticulum gene expression in pressure overload cardiac hypertrophy by etomoxir. Faseb J 10 (1996) 1303-1309
172. Zhao G., Jeoung N.H., Burgess S.C., Rosaaen-Stowe K.A., Inagaki T., Latif S., Shelton J.M., McAnally J., Bassel-Duby R., Harris R.A., Richardson J.A., and Kliewer S.A. Overexpression of pyruvate dehydrogenase kinase 4 in heart perturbs metabolism and exacerbates calcineurin-induced cardiomyopathy. Am J Physiol Heart Circ Physiol (2007)
173. Zhou G., Myers R., Li Y., Chen Y., Shen X., Fenyk-Melody J., Wu M., Ventre J., Doebber T., Fujii N., Musi N., Hirshman M.F., Goodyear L.J., and Moller D.E. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108 (2001) 1167-1174
174. Zong H., Ren J.M., Young L.H., Pypaert M., Mu J., Birnbaum M.J., and Shulman G.I. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci USA 99 (2002) 15983-15987