Partial fatty acid oxidation inhibitors for stable angina

Bibliography

• OPIE L: The heart: physiology, from cell to circulation. Lippincott-Raven, Philadelphia, USA (1998).
   Google Scholar
• •This textbook presents a thorough overview of myocardial energy metabolism.
   Google Scholar
• STANLEY WC, LOPASCHUK GD, HALL JL, MCCORMACK JG: Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions: potential for pharmacological interventions. Cardiovasc. Res. (1997) 33:243–257.
   PubMed Web of Science ®Google Scholar
• LIEDTKE AJ: Alterations in carbohydrate and lipid metabolism in the acutely ischaemic heart. Frog. Cardiovasc. DA (1981) 23:321–326.
   PubMed Web of Science ®Google Scholar
• MCNULTY PH, SINUSAS AJ, SHI CQ, et al.: Glucose metabolism distal to a critical coronary stenosis in a canine model of low-flow myocardial ischaemia. Clin. Invest. (1996) 98:62–69.
   Google Scholar
• STANLEY WC: Changes in cardiac metabolism: a critical step from stable angina to ischaemic cardiomyopathy. Euro. Heart .1. (2001) 3\(Suppl. 0):02–07.
   Google Scholar
• LOPASCHUK GD, BELKE DD, GAMBLE J, ITOI T, SCHONEKESS BO: Regulation of fatty acid oxidation in the mammalian heart in health and disease. Biochini. Biophys. Acta (1994) 1213:263–276.
   PubMed Web of Science ®Google Scholar
• TAEGTMEYER H: Energy metabolism inthe heart. Curr. Prob. Cardiol (1994) 19:59–113.
   PubMed Web of Science ®Google Scholar
• VAN DER VUSSE GJ, VAN BILSEN M, GLATZ JF: Cardiac fatty acid uptake and transport in health and disease. Cardiovasc. Res. (2000) 45:279–293.
   PubMed Web of Science ®Google Scholar
• BALABAN RS, KANTOR HL, KATZ LA, BRIGGS RW: Relation between work and phosphate metabolite in the in vivo paced mammalian heart. Science (1986) 232:1121–1123.
   PubMed Web of Science ®Google Scholar
• WISNESKI JA, GERTZ EW, NEESE RA, MMR M: Myocardial metabolism of free fatty acids: studies with MC-labeled substrates in humans.' Clin. Invest. (1987) 79:359–366.
   Google Scholar
• SCHULZ H: Regulation of fatty acid oxidation in heart." Num (1994) 124:165–171.
   Google Scholar
• GERTZ EW, WISNESKI JA, STANLEY WC, NEESE RA: Myocardial substrate utilization during exercise in humans: Dual carbon-labeled carbohydrate isotope experiments.' Clin. Invest. (1988) 82: 2017-2025.
   Google Scholar
• WISNESKI JA, GERTZ EW, NEESE RA, GRUENKE LD, MORRIS DL, CRAIG JC: Metabolic fate of extracted glucose in normal human myocardium. I Clin. Invest. (1985) 76:18 19–1827.
   Google Scholar
• WISNESKI JA, STANLEY WC, GERTZ EW, NEESE RA: Effects of hyperglycemia on myocardial glycolytic activity in normal humans.' Clin. Invest. (1990) 85: 1648-1656.
   Google Scholar
• KERBEY AL, RANDLE PJ, COOPER RH,WHITEHOUSE S, PASK HT, DENTON RM: Regulation of pyruvate dehydrogenase. Biochein. J. (1976) 154:327–348.
   PubMed Web of Science ®Google Scholar
• WIELAND 0, FUNCKE HV, LOFFLER G: Interconversion of pyruvate dehydrogenase in rat heart muscle upon perfusion with fatty acids or ketone bodies. FEBS Led (1971) 15:295–298.
   PubMed Web of Science ®Google Scholar
• WIELAND 0, SIESS E, SCHULZE-WETHMAR FH, FUNCKE HG, WINTON B: Active and inactive forms of pyruvate dehydrogenase in rat heart and kidney: effect of diabetes, fasting and refeeding on pyruvate dehydrogenase interconversion. Arch. Biochein. Biophys. (1971) 143:593–601.
   PubMed Web of Science ®Google Scholar
• HANSFORD RG, 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. Biochein. Biophys. (1978) 191:65–81.
   PubMed Web of Science ®Google Scholar
• •Important study demonstrating the critical role of fatty acid oxidation in the inhibition of flux through pyvuate dehydrogenase in the heart.
   Google Scholar
• MCCORMACK JG, HALESTRAP AP, DENTON RM: Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physic] Rev (1990) 70:391–425.
   PubMed Web of Science ®Google Scholar
• WU P, SATO J, ZHAO Y, JASKIEWICZ J, POPOV KM, HARRIS RA: Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart. Biochem. J. (1998) 329:197–201.
   PubMed Web of Science ®Google Scholar
• RANDLE PJ, HALES CN, GARLAND PB, NEWSHOLME EA: The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet (1963) ii:785–789.
   Google Scholar
• RANDLE PJ, NEWSHOLME EA, GARLAND PB: Regulation of glucose uptake by muscle. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan diabetes and starvation, on the uptake and metabolic fate of glucose in rat heart and diaphragm muscles. Biochem. J. (1964) 93:652–665.
   Google Scholar
• LASSERS BW, WAHLQVIST ML, KAIJSER L, CARLSON LA: Effect of nicotinic acid on myocardial metabolism in man at rest and during exercise. Appl Physic] (1972) 33:72–80.
   PubMed Web of Science ®Google Scholar
• LOPASCHUK GD, SPAFFORD M, DAVIES NJ, WALL SR: Glucose and palmitate oxidation in isolated working rat hearts reperfused following a period of transient global ischaemia. Circ. Res (1990) 66:546–553.
   PubMed Web of Science ®Google Scholar
• SCHWARTZ GG, GREYSON C, WISNESKI JA, GARCIA J: Inhibition of fatty acid metabolism alters myocardial high-energy phosphates in vivo. Am. I Physiol. (1994) 267:H224–H231.
   PubMed Web of Science ®Google Scholar
• KANTOR PF, LUCIEN A, KOZAK R, LOPASCHUK GD: The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme a thiolase. Circ. Res. (2000) 86:580–588.
   PubMed Web of Science ®Google Scholar
• ••Demonstrates that trirnetazidine suppressesmyocardial fatty acid oxidation via inhibition of long-chain 3-ketoacyl coenzyme A thiolase.
   Google Scholar
• MCCORMACK JG, STANLEY WC, WOLFF AA: Pharmacology of ranolazine: a novel metabolic modulator for the treatment of angina. Gen. Pharmacol (1998) 30:639–645.
   PubMedGoogle Scholar
• ••This review covers the predinical andclinical pharmacology of ranolazine.
   Google Scholar
• PARKER JO, WEST RO, CASE RB, CHIONG MA: Temporal relationships of myocardial lactate metabolism, left ventricular function, and ST-segment depression during angina precipitate by exercise. Circulation (1969) 40:97–111.
   PubMed Web of Science ®Google Scholar
• PARKER JO, CHIONG MA, WEST RO, CASE RB: Sequential alterations in myocardial lactate metabolism, ST-segments, and left ventricular function during angina induced by atrial pacing. Circulation (1969) 40:113–131.
   PubMed Web of Science ®Google Scholar
• CHANDLER MP, HUANG H, MCELFRESH TA, STANLEY WC: Increased myocardial glycolysis and lactate production despite continued fatty acid uptake during demand-induced ischaemia. Am..! Physiol (2002): In Press.
   Google Scholar
• MIYAZAKI S, GOTO Y, GUTH BD, MIURA T, INDOLFI C, ROSS J JR: Changes in regional myocardial function and external work in exercising dogs with ischaemia. Am. J. Physiol. (1993) 264:H110–116.
   PubMed Web of Science ®Google Scholar
• FABIATO A, FABIATO F: Effects of pH onthe myofilaments and the sarcoplasmic reticulum of skinned cells from cardiac and skeletal muscles. J. Physiol (1978) 276:233–255.
   PubMed Web of Science ®Google Scholar
• MURPHY E, PERLMAN M, LONDON RE, STEENBERGEN C: Amiloride delays the ischaemia-induced rise in cytosolic free calcium. Circ. Res. (1991) 68:1250–1258.
   PubMed Web of Science ®Google Scholar
• STANLEY WC, HERNANDEZ LA, SPIRES DA, BRINGAS J, WALLACE S, MCCORMACK JG: Pyruvate dehydrogenase activity and malonyl CoA levels in normal and ischaemic swine myocardium: effects of dichloroacetate. Ma Cell. Cardiol (1996) 29:905–914.
   Web of Science ®Google Scholar
• SCHODER H, KNIGHT RJ, KOFOED KF, SCHELBERT HR, BUXTON DB: Regulation of pyruvate dehydrogenase activity and glucose metabolism in post-ischaemic myocardium. Biochim. Biophys. Acta (1998) 1406:62–72.
   PubMed Web of Science ®Google Scholar
• STANIFORTH AD: Contemporary management of chronic stable angina. Drugs Aging (2001) 18:109–121.
   PubMed Web of Science ®Google Scholar
• PEPINE CJ, COHN PF, DEEDWANIA PC et al: Effects of treatment on outcome in mildly symptomatic patients with ischaemia during daily life. The Atenolol Silent Ischaemia Study (ASIST). Circulation (1994) 90:762–768.
   PubMed Web of Science ®Google Scholar
• AKRAS F, JACKSON G: Efficacy of nifedipine and isosorbide mononitrate in combination with atenolol in stable angina. Lancet (1991) 338:1036–1039.
   PubMed Web of Science ®Google Scholar
• FOX KM, MULGAHY D, FINDLAY I, FORD I, DARGIE HJ, on behalf of the TIBET Study Group: The Total Ischaemic Burden European Trial (TIBET). Eur. Heart J. (1996) 17:96–103.
   PubMed Web of Science ®Google Scholar
• •Large international trial showing no added benefit with combination therapy for stable angina.
   Google Scholar
• PACKER M: Combined beta-adrenergic and calcium-entry blockade in angina pectoris. N Engl. J. Med. (1989) 320:709–718.
   PubMed Web of Science ®Google Scholar
• KELLY DP, STRAUSS AW: Inherited Cardiomyopathies. N Engl. I Med. (1994) 330:913–919.
   PubMed Web of Science ®Google Scholar
• CORR PB, YAMADA KA: Selected metabolic alterations in the ischaemic heart and their contributions to arrhythmogenesis. Herz (1995) 20:156–168.
   PubMed Web of Science ®Google Scholar
• OLIVER MF, OPIE LH: Effects of glucose and fatty acids on myocardial ischaemia and arrhythmias Lancet (1994) 343:155–158.
   Google Scholar
• ••Excellent brief overview on the metabolictherapy for ischaemia and arrhythmias.
   Google Scholar
• STEPHENS TW, HIGGINS AJ, COOK GA, HARRIS RA: Two mechanisms produce tissue-specific inhibition of fatty acid oxidation by oxfenicine. Biochem. J. (1985) 227:651–660.
   PubMed Web of Science ®Google Scholar
• BARNISH IT, CROSS PE, DANILEWICZ JC, DICKINSON RP, STOPHER DA: Promotion of carbohydrate oxidation in the heart by some phenylglyoxylic acids. J. Med. Chem. (1981) 24:399–404.
   PubMed Web of Science ®Google Scholar
• DRAKE-HOLLAND AJ, PASSINGHAM JE: The effect of Oxfenicine on cardiac carbohydrate metabolism in intact dogs. Basic Res. Cardiol (1983) 78:19–27.
   PubMed Web of Science ®Google Scholar
• BURGES RA, GARDINER DG, HIGGINSAJ: Protection of the ischaemic dog heart by oxfenicine. Life Sci (1981) 29:1847–1853.
   PubMed Web of Science ®Google Scholar
• HIGGINS AJ, MORVILLE M, BURGES RA, GARDINER DG, PAGE MG, BLACKBURN KJ: Oxfenicine diverts rat muscle metabolism from fatty acid to carbohydrate oxidation and protects the ischaemia rat heart. Life Sci. (1980) 27:963–970.
   PubMed Web of Science ®Google Scholar
• HIGGINS AJ, MORVILLE M, BURGES RA, BLACKBURN KJ: Mechanism of action of oxfenicine on muscle metabolism. Biochem. Biophys. Res. Comm. (1981) 100:291–296.
   PubMed Web of Science ®Google Scholar
• BELLEMIN-BAURREAU J, POIZOT A, HICKS PE, ARMSTRONG JM: An in vitro method for the evaluation of antiarrhythmic and antischaemic agents by using programmed electrical stimulation of rabbit heart. J. Pharinacol Toxicol Methods (1994) 31(1):31–40.
   PubMed Web of Science ®Google Scholar
• BIELEFELD DR, VARY TC, NEELY JR: Inhibition of carnitine palmitoyl-CoA transferase activity and fatty acid oxidation by lactate and oxfenicine in cardiac muscle../. Mol Cell Cardiol (1985) 17:619–625.
   PubMed Web of Science ®Google Scholar
• VIK-MO H, MJOS OD, NEELY JR et al.: Limitation of myocardial infarct size by metabolic interventions that reduce accumulation of fatty acid metabolites in ischaemic myocardium. Am. Heart J. (1986) 111:1048.
   PubMed Web of Science ®Google Scholar
• YAMADA KA, MCHOWAT J, YAN G et al.: Cellular uncoupling induced by accumulation of long-chain acetylcarnitine during ischaemia. Circ. Res. (1994) 74:83–95.
   PubMed Web of Science ®Google Scholar
• CHANDLER MP, MCELFRESH TA, HUANG H, STANLEY WC: Partial inhibition of fatty acid oxidation decreases lactate production and increases regional contractile work during ischaemia induced by dobutamine with flow restriction. FASEB j. (2002): Abstract, In Press.
   Google Scholar
• BERGMAN G, ATKINSON L, METCALFE J, JACKSON J, JEWITT DE: Beneficial effect of enhanced myocardial carbohydrate utilisation after oxfenicine (L-hydroxyphenylglycine) in angina pectoris. Ear: Heart J. (1980) 1:247–253.
   PubMedGoogle Scholar
• BROWN MJ, HOROWITZ JD, MASHFORD ML: A double-blind trial of perhexiline maleate in the prophylaxis of angina pectoris. Med. J. Aust. (1976) 1:260–263.
   PubMed Web of Science ®Google Scholar
• BUNDE CA, GRUPP IA, GRUPP G: Effects of the antianginal agent perhexilene maleate on exercise induced tachycardia in human volunteers. Fed Proc. (1969) 28:672.
   Google Scholar
• HIRSHLEIFER I: Perhexiline maleate in the treatment of angina pectoris. Carr: Thec Res. Clin. Exp. (1969) 11:99–105.
   PubMed Web of Science ®Google Scholar
• HORGAN JH, O'CALLAGHAN WG, TEO KK: Therapy of angina pectoris with low-dose perhexiline. Cardiovasc. Pharmacol (1981) 3:566–572.
   PubMed Web of Science ®Google Scholar
• PEPINE CJ, SCHANG SJ, BEMILLER CR: Effects of perhexiline on symptomatic and haemodynamic responses to exercise in patients with angina pectoris. Am. I Cardiol (1974) 33:306–312.
   Web of Science ®Google Scholar
• PILCHER J: Comparative trial of perhexilinemaleate and oxprenolol in patients with angina pectoris. Postgrad. Med. J. (1978) 54: 663–667.
   PubMed Web of Science ®Google Scholar
• COLE PL, BEAMER AD, MCGOWAN N et al.: Efficacy and safety of perhexiline maleate in refractory angina. A double-blind placebo-controlled clinical trial of a novel antianginal agent. Circulation (1990) 81:1260–1270.
   Google Scholar
• JEFFREY FMH, ALVAREZ L, DICZKU V, SHERRY AD, MALLOY CR: Direct evidence that perhexiline modifies myocardial substrate utilization from fatty acids to lactate. .1 Cardiovasc. Pharinacol (1995) 25:469–472.
   PubMed Web of Science ®Google Scholar
• KENNEDY JA, KIOSOGLOUS AJ, MURPHY GA, PELLE MA, HOROWITZ JD: Effect of perhexiline and oxfenicine on myocardial function and metabolism during low-flow ischaemia/reperfusion in the isolated rat heart. Cardiovasc. Pharinacol (2000) 36:794–801.
   PubMed Web of Science ®Google Scholar
• KENNEDY JA, UNGER SA, HOROWITZ JD: Inhibition of carnitine palmitoyltransferase-1 in rat heart and liver by perhexiline and amiodarone. Biochem. Pharinacol (1996) 52:273–280.
   PubMed Web of Science ®Google Scholar
• HOROWITZ JD, SIA ST, MACDONALD PS, GOBLE AJ, LOUIS WJ: Perhexiline maleate treatment for severe angina pectoris-correlations with pharmacokinetics. Int. J. Cardiol (1986) 13:219–229.
   PubMed Web of Science ®Google Scholar
• HUSSEIN R, CHARLES BG, MORRIS RG, RASIAH RL: Population pharmacokinetics of perhexiline from very sparse, routine monitoring data. Thec Drug Monit. (2001) 23:636–643.
   PubMed Web of Science ®Google Scholar
• MORGAN MY, RESHEF R, SHAH RR, OATES NS, SMITH RL, SHERLOCK S: Impaired oxidation of debrisoquine in patients with perhexiline liver injury. Gut (1984) 25:1057–1064.
   PubMed Web of Science ®Google Scholar
• SHAH RR, OATES NS, IDLE JR, SMITH RL, LOCKHART JDF: Impaired oxidation of debrisoquine in patients with perhexiline neuropathy. Br. Med. J. (1982) 284:295–299.
   PubMed Web of Science ®Google Scholar
• SLOAN TP, MAHGOUB A, LANCASTER R, SMITH RL: Polymorphism of carbon oxidation of drugs and clinical implications. Br. Med. J. (1978) 2:655–657.
   PubMed Web of Science ®Google Scholar
• LOPASCHUK GD, WALL SR, OLLEY PM, DAVIES NJ: Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects hearts from fatty acid-induced ischaemia injury independent of changes in long chain acylcarnitine. Circ. Res. (1988) 63:1036–1043.
   PubMed Web of Science ®Google Scholar
• LOPASCHUK GD, SPAFFORD M, DAVIES NJ, WALL SR: Glucose and palmitate oxidation in isolated working rat hearts reperfused following a period of transient global ischaemia. Circ. Res. (1990) 66:546–553.
   PubMed Web of Science ®Google Scholar
• BRISTOW M: Etomoxir: a new approach to treatment of chronic heart failure. Lancet (2000) 356:1621–1622.
   PubMed Web of Science ®Google Scholar
• SCHMIDT-SCHWEDAS, HOLUBARSCH: First clincial trial with etomwdr in patients with chronic congestive heart failure. Clin. Sci (2000) 99:27–35.
   PubMed Web of Science ®Google Scholar
• VETTER R, RUPP H: CPT-I inhibition by etomwdr has a chamber-related action on cardiac sarcoplasmic reticulum and isomyosins. Am. Physiol (1994) 267:H2091–H2099.
   PubMed Web of Science ®Google Scholar
• ZARAIN-HERZBERG A, RUPP H, ELIMBAN V, DHALLA NS: Modification of sarcoplasmic reticulum gene expression in pressure overload cardiac hypertrophy by etomwdr. FASEB J. (1996) 10:1303–1309.
   PubMed Web of Science ®Google Scholar
• RUPP H, ELIMBAN V, DHALLA NS: Modification of subcellular organelles in pressure-overloaded heart by etomoxir, a carnitine palmitoyltransferase I inhibitor. FASEB (1992) 6:2349–2353.
   PubMed Web of Science ®Google Scholar
• TURCANI M, RUPP H: Etomoxir improvesleft ventricular performance of pressure-overloaded rat heart. Circulation (1997) 96:3681–3686.
   PubMed Web of Science ®Google Scholar
• TURCANI M, RUPP H: Modification of left ventricular hypertrophy by chronic etomwdr treatment. Br. J. Pharinacol (1999) 126:501–507.
   PubMed Web of Science ®Google Scholar
• MCCLELLA KJ, PLOSKER GL: Trimetazidine. A review of its use in stable angina pectoris and other coronary conditions. Drugs (1999) 58:143–157.
   Google Scholar
• FANTINI E, DEMAISON L, SENTEX E, GRYNBERG A, ATHIAS P: Some biochemical aspects of the protective effect of trimetazidine on rat cardiomyocytes during hypoxia and reoxygenation. I Mol Cell Cardiol (1994) 26:949–958.
   PubMed Web of Science ®Google Scholar
• KANTOR PF, LUCIEN A, KOZAK R, LOPASCHUK GD: The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ. Res. (2000) 86:580–588.
   PubMed Web of Science ®Google Scholar
• LOPASCHUK GD: Optimizing cardiac energy metabolism: how can fatty acid and carbohydrate metabolism be manipulated? Coron. Artery Dis (2001) 12\(Suppl. 1): s8–s11.
   Google Scholar
• BOUCHER FR, HEARSE DJ, OPIE LH: Effects of trimetazidine on ischaemic contracture in isolated perfused rat hearts. Cardiovasc. Pharmacol (1994) 24:45–49.
   PubMed Web of Science ®Google Scholar
• EL BANANI H, BERNARD M, BAETZ D et al.: Changes in intracellular sodium and pH during ischaemia-reperfusion are attenuated by trimetazidine. Comparison between low- and zero-flow ischaemia. Cardiovasc. Res. (2000) 47:688–696.
   Google Scholar
• LAVANCHY N, MARTIN J, ROSSI A: Anti-ischaemia effects of trimetazidine: 31P-NMR spectroscopy in the isolated rat heart. Arch. Int. Phannacodyn. (1987) 286:97–110.
   PubMedGoogle Scholar
• DALLA-VOLTA S, MARAGLINO G, DELLA-VALENTINA P, VIENA P, DESIDERI A: Comparison of trimetazidine with nifedipine in effort angina: a double-blind, crossover study. Cardiovasc. Drugs The]: (1990) 4:853–860.
   PubMed Web of Science ®Google Scholar
• DETRYJM, SELLIER P, PENNAFORTE S, COKKINOS D, DARGIE H, MATHES P: Trimetazidine: a new concept in the treatment of angina. Comparison with propranolol in patients with stable angina. Br: J. Clin. Phannacol (1994) 37:279–288.
   PubMed Web of Science ®Google Scholar
• MANCHANDASC, KRISCHNASWAMI S: Combination treatemt with trimetazidine and diltiazem in stable angina pectoris. Heart (1997) 78:353–357.
   PubMed Web of Science ®Google Scholar
• SELLIER P: Chronic effects of trimetazidine on ergometric parameters in effort angina. Cariovasc. Drugs The]: (1990) 4:822–823.
   PubMed Web of Science ®Google Scholar
• SZWED H, SADOWSKI Z, ELIKOWSKI W et al.: Combination treatment in stable effort angina using trimetazidine and metoprolol. Results of a randomized, double-blind, multicentre study (TRIMPOL II). Euro. Heart .1. (2001) 22:2267-2274.
   Google Scholar
• ••Recent controlled trial demonstrating clearefficacy with trimetazidine on top of a a-blocker.
   Google Scholar
• Effect of 48-h intravenous trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy; A double-blind, placebo-controlled, randomized trial. The EMIP-FR Group. European Myocardial Infarction Project-Free Radicals. Eur Heart (2000) 21:1537–1546.
   Google Scholar
• BELLARDINELLI R, PURCARO A: Effects of trimetazidine on the contractile response of chronically dysfunctional myocardium to low-dose dobutamine in ischaemic cardiomyopathy. Europ. Heart .1. (2001) 23:2164–2170.
   Web of Science ®Google Scholar
• •Intriguing small trial showing improved LV function in ischaemic heart failure patients.
   Google Scholar
• D'HAHAN N, TAOUIL K, DASSOULI A, MOREL JE: Long-term therapy with trimetazidine in cardiomyopathic Syrian hamster BIO 14:6. Euro. J. Phannacol. (1997) 328:163–174.
   PubMed Web of Science ®Google Scholar
• SELLIER P, BROUSTET JP: Efficacy at trough and safety of trimetazidine MR 35 mg in patients with stable angina pectoris. Cardiovasc. Drugs Therapy (2001) 15\(Suppl. 1):81.
   Google Scholar
• •Abstract describing the efficacy of maintained release" formulation of trimetazidine.
   Google Scholar
• CLARKE B, WYATT KM, MCCORMACK JG: Ranolazine increases active pyruvate dehydrogenase in perfused normoxic rat hearts: evidence for an indirect mechanism. Ma Cell Cardiol (1996) 28:341–350.
   PubMed Web of Science ®Google Scholar
• SCHOFIELD RS, HILL JA: The use of ranolazine in cardiovascular disease. Expert Opin. Livestig. Drugs (2002) 11:117–123.
   PubMed Web of Science ®Google Scholar
• ••Recent overview of the clinicalpharmacology of ranolazine.
   Google Scholar
• MCCORMACK JG, BARR RL, WOLFF AA, LOPASCHUK GD: Ranolazine stimulates glucose oxidation in normoxic, ischaemic, and reperfused ischaemic rat hearts. Circulation (1996) 93:135–145.
   PubMed Web of Science ®Google Scholar
• ••Preclinical studies demonstrating increasedmyocardial glucose oxidation with ranolazine.
   Google Scholar
• MCCORMACK JG, BARACOS VE, BARR R, LOPASCHUK GD: Effects of ranolazine on oxidative substrate preference in epitrochlearis muscle. Appl. Physiol (1996) 81:905–910.
   PubMed Web of Science ®Google Scholar
• CLARKE B, M. S, PATMORE L, MCCORMACK JG: Protective effects of ranolazine in guinea-pig hearts during low-flow ischaemia and their association with increases in active pyruvate dehydrogenase. Br: J. Pharmacol (1993) 109:748–750.
   PubMed Web of Science ®Google Scholar
• GRALINSKI MR, BLACK SC, KILGORE KS, CHOU AY, MCCORMACK JG, LUCCHESI BR: Cardioprotective effects of ranolazine (RS-43285) in the isolated perfused rabbit heart. Cardiovasc. Res. (1994) 28:1231–1237.
   PubMed Web of Science ®Google Scholar
• ALLELY MC, BROWN CM, KENNY BA, KILPATRICK AT, MARTIN A, SPEDDING M: Modulation of alpha 1-adrenoceptors in rat left ventricle by ischaemia and acetyl carnitines: protection by ranolazine. Cardiovasc. Pharmacol (1993) 21:869–873.
   PubMed Web of Science ®Google Scholar
• COCCO G, ROUSSEAU ME BOUVY T et al.: Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina pectoris patients treated with beta-blocker or diltiazem. Cardiovasc. Phannacol. (1992) 20:131–138.
   Google Scholar
• •This interesting clinical trial has never been published as a full paper.
   Google Scholar
• PEPINE CJ, WOLFF AA FOR THE RANOLAZINE STUDY GROUP: A controlled trial with a novel anti-ischaemic agent, ranolazine, in chronic stable angina pectoris that is responsive to conventional antianginal agents. Arm Cardiol (1999) 84:46–50.
   PubMed Web of Science ®Google Scholar
• ROUSSEAU ME VISSER FG, BAX JJ et al.: Ranolazine: antianginal therapy with a novel mechanism: placebo controlled comparison versus atenolol. Eut: Heart J. (1994) 15 (Suppl.):95.
   Google Scholar
• THADANI U, EZEKOWITZ M, FENNEY L, CHIANG YK: Double-blind efficacy and safety study of a novel anti-ischaemic agent, ranolazine, versus placebo in patients with chronic stable angina pectoris. Ranolazine Study Group. Circulation (1994) 90:726-734.WOLFF AA FOR THE MARISA INVESTIGATORS: Monotherapy assessment of ranolazine in stable angina. Am. Coll. Cardiol (2000) 35(Suppl. A):408A.
   Google Scholar
• This is the definitive trial with ranolazine montherapy and has only been published in abstract form.
   Google Scholar
• DEQUATTRO V, SKETTINO S, CHAITMAN B et al.: Comparative antianginal efficacy and tolerability of ranolazine in diabetic and nondiabetic patients: results of the MARISA trial. Am. College Cardiol 50th Annual Scientific Session (2001).
   Google Scholar
• JANSKY P, SKETTINO S, CHAITMAN BR et al.: Comparative antianginal efficacy of ranolazine in young (65 years) versus elderly (> 65 years) patients: results of the MARISA trial. Circulation (2000) 102 (Suppl. II) :11–72.
   Google Scholar
• CHAITMAN BR FOR THE CARISA INVESTIGATORS: Improved exercise capacity using a novel pFOX inhibitor as antianginal therapy: results of the Combination Assessment of Ranolazine In Stable Angina (CARISA). Circulation (2001) 104:2B.
   PubMed Web of Science ®Google Scholar
• ••The CARISA trial has only been published in abstract form.
   Google Scholar
• STANLEY WC, MISHIMA T, BIESIADECKI BJ et al.: Ranolazine, a partial fatty acid oxidation inhibitor, improves left ventricular performance in dogs with chronic heart failure. Euro..1. Heart Failure (2000) 2 (Suppl. 2):97.
   Google Scholar
• STANLEY WC, CHANDLER MP, MISHIMA T et al.: Ranolazine, a partial fatty acid oxidation (pFOX) inhibitor, improves left ventricular efficiency in dogs with heart failure. Cardiovasc. Drugs Ther. (2001) 15\(Suppl. 1):107.
   Google Scholar
• CHAITMAN BR, SKETTINO S, DEQUATTRO V et al.: Improved exercise performance on ranolazine in patients with chronic angina and a history of heart failure: the MARISA Trial. J. Ain. Col. Cardiol. (2001) Suppl.
   Google Scholar