Cardiac metabolism and arrhythmias

Circulation: Arrhythmia and Electrophysiology

Volumn 2, Issue 3, 2009, Pages 327-335

  Barth, Andreas S ^a   Tomaselli, Gordon F ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Arrhythmia; Diabetes mellitus; Ion channels; Ischemia; Metabolism

Indexed keywords

ADENOSINE TRIPHOSPHATASE (CALCIUM); ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); ADENOSINE TRIPHOSPHATE SENSITIVE POTASSIUM CHANNEL; ADENYLATE KINASE; CALCIUM; CALCIUM CHANNEL L TYPE; GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE; INWARDLY RECTIFYING POTASSIUM CHANNEL SUBUNIT KIR6.2; PERHEXILINE MALEATE; PROTEIN SERCA2; RANOLAZINE; REACTIVE OXYGEN METABOLITE; RYANODINE RECEPTOR 2; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; SODIUM; SODIUM CALCIUM EXCHANGE PROTEIN; SODIUM PROTON EXCHANGE PROTEIN 1; TRIMETAZIDINE; UNCLASSIFIED DRUG;

CALCIUM HOMEOSTASIS; CARDIOMYOPATHY; EXCITATION CONTRACTION COUPLING; HEART ARRHYTHMIA; HEART ATRIUM FIBRILLATION; HEART ELECTROPHYSIOLOGY; HEART FAILURE; HEART LEFT VENTRICLE HYPERTROPHY; HEART MUSCLE ISCHEMIA; HEART MUSCLE METABOLISM; HEART VENTRICLE REMODELING; HUMAN; MITOCHONDRIAL MEMBRANE POTENTIAL; NONHUMAN; PRIORITY JOURNAL; REPERFUSION INJURY; REVIEW; SODIUM BALANCE;

ARRHYTHMIAS, CARDIAC; DIABETES MELLITUS; ENERGY METABOLISM; HUMANS; ION CHANNELS; MYOCARDIAL ISCHEMIA; MYOCARDIUM;

EID: 70349583444     PISSN: 19413149     EISSN: 19413084     Source Type: Journal    
DOI: 10.1161/CIRCEP.108.817320     Document Type: Review

References (102)

1. Cobb LA, Fahrenbruch CE, Olsufka M, Copass MK. Changing incidence of out-of-hospital ventricular fibrillation, 1980 -2000. JAMA. 2002; 288:3008 -3013.
2. Myerburg RJ. Sudden cardiac death: exploring the limits of our knowledge. J Cardiovasc Electrophysiol. 2001; 12:369 -381.
3. Zipes DP, Wellens HJ. Sudden cardiac death. Circulation. 1998; 98: 2334-2351.
4. Nass RD, Aiba T, Tomaselli GF, Akar FG. Mechanisms of disease: ion channel remodeling in the failing ventricle. Nat Clin Pract Cardiovasc Med. 2008; 5:196 -207.
5. Shah M, Akar FG, Tomaselli GF. Molecular basis of arrhythmias. Circulation. 2005; 112:2517-2529.
6. Barth E, Stammler G, Speiser B, Schaper J. Ultrastructural quantitation of mitochondria and myofilaments in cardiac muscle from 10 different animal species including man. J Mol Cell Cardiol. 1992; 24:669-681.
7. O'Rourke B, Cortassa S, Aon MA. Mitochondrial ion channels: gatekeepers of life and death. Physiology (Bethesda). 2005; 20:303-315. (Pubitemid 41457396)
8. Murphy E, Steenbergen C. Ion transport and energetics during cell death and protection. Physiology (Bethesda). 2008; 23:115-123.
9. John SA, Kondo R, Wang SY, Goldhaber JI, Weiss JN. Connexin-43 hemichannels opened by metabolic inhibition. J Biol Chem. 1999; 274: 236-240.
10. Kondo RP, Wang SY, John SA, Weiss JN, Goldhaber JI. Metabolic inhibition activates a non-selective current through connexin hemichannels in isolated ventricular myocytes. J Mol Cell Cardiol. 2000; 32:1859 -1872.
11. Manjunath CK, Page E. Cell biology and protein composition of cardiac gap junctions. Am J Physiol. 1985; 248:H783-H791.
12. Neubauer S, Newell JB, Ingwall JS. Metabolic consequences and predictability of ventricular fibrillation in hypoxia: a 31P- and 23Nanuclear magnetic resonance study of the isolated rat heart. Circulation. 1992; 86:302-310.
13. Tomaselli GF, Beuckelmann DJ, Calkins HG, Berger RD, Kessler PD, Lawrence JH, Kass D, Feldman AM, Marban E. Sudden cardiac death in heart failure: the role of abnormal repolarization. Circulation. 1994; 90: 2534-2539.
14. Veglio M, Chinaglia A, Cavallo-Perin P. QT interval, cardiovascular risk factors and risk of death in diabetes. J Endocrinol Invest. 2004; 27: 175-181.
15. Tomaselli GF, Marban E. Electrophysiological remodeling in hypertrophy and heart failure. Cardiovasc Res. 1999; 42:270 -283.
16. Hansen PS, Clarke RJ, Buhagiar KA, Hamilton E, Garcia A, White C, Rasmussen HH. Alloxan-induced diabetes reduces sarcolemmal Na+-K+ pump function in rabbit ventricular myocytes. Am J Physiol Cell Physiol. 2007; 292:C1070-C1077.
17. Shivkumar K, Deutsch NA, Lamp ST, Khuu K, Goldhaber JI, Weiss JN. Mechanism of hypoxic K loss in rabbit ventricle. J Clin Invest. 1997; 100:1782-1788.
18. Janse MJ, van Capelle FJ, Morsink H, Kleber AG, Wilms-Schopman F, Cardinal R, d'Alnoncourt CN, Durrer D. Flow of " injury" current and patterns of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts: evidence for two different arrhythmogenic mechanisms. Circ Res. 1980; 47:151-165.
19. Liu T, O'Rourke B. Enhancing mitochondrial Ca2+ uptake in myocytes from failing hearts restores energy supply and demand matching. Circ Res. 2008; 103:279 -288.
20. Huser J, Blatter LA, Sheu SS. Mitochondrial calcium in heart cells: beat-to-beat oscillations or slow integration of cytosolic transients? J Bioenerg Biomembr. 2000; 32:27-33.
21. Saks V., Dzeja P, Schlattner U, Vendelin M, Terzic A, Wallimann T. Cardiac system bioenergetics: metabolic basis of the Frank-Starling law. J Physiol. 2006; 571:253-273.
22. Maack C, Cortassa S, Aon MA, Ganesan AN, Liu T, O'Rourke B. Elevated cytosolic Na+ decreases mitochondrial Ca2+ uptake during excitation-contraction coupling and impairs energetic adaptation in cardiac myocytes. Circ Res. 2006; 99:172-182.
23. Sedova M, Dedkova EN, Blatter LA. Integration of rapid cytosolic Ca2+ signals by mitochondria in cat ventricular myocytes. Am J Physiol Cell Physiol. 2006; 291:C840-850.
24. Goldhaber JI, Parker JM, Weiss JN. Mechanisms of excitationcontraction coupling failure during metabolic inhibition in guinea-pig ventricular myocytes. J Physiol. 1991; 443:371-386.
25. Hool LC. Hypoxia increases the sensitivity of the L-type Ca(2+) current to beta-adrenergic receptor stimulation via a C2 region-containing protein kinase C isoform. Circ Res. 2000; 87:1164 -1171.
26. Lederer WJ, Nichols CG, Smith GL. The mechanism of early contractile failure of isolated rat ventricular myocytes subjected to complete metabolic inhibition. J Physiol. 1989; 413:329 -349.
27. Losito VA, Tsushima RG, Diaz RJ, Wilson GJ, Backx PH. Preferential regulation of rabbit cardiac L-type Ca2+ current by glycolytic derived ATP via a direct allosteric pathway. J Physiol. 1998; 511(Pt 1):67-78.
28. Chantawansri C, Huynh N, Yamanaka J, Garfinkel A, Lamp ST, Inoue M, Bridge JH, Goldhaber JI. Effect of metabolic inhibition on coupling behavior in rabbit ventricular myocytes. Biophys J. 2008; 94:1656 -1666.
29. Shaw RM, Rudy Y. Electrophysiologic effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration. Cardiovasc Res. 1997; 35:256-272. (Pubitemid 27372038)
30. Mohabir R, Lee HC, Kurz RW, Clusin WT. Effects of ischemia and hypercarbic acidosis on myocyte calcium transients, contraction, and pHi in perfused rabbit hearts. Circ Res. 1991; 69:1525-1537.
31. Overend CL, Eisner DA, O'Neill SC. Altered cardiac sarcoplasmic reticulum function of intact myocytes of rat ventricle during metabolic inhibition. Circ Res. 2001; 88:181-187.
32. Xu L, Mann G, Meissner G. Regulation of cardiac Ca2+ release channel (ryanodine receptor) by Ca2+ , H+, Mg2+, and adenine nucleotides under normal and simulated ischemic conditions. Circ Res. 1996; 79: 1100-1109.
33. Meissner G, Henderson JS. Rapid calcium release from cardiac sarcoplasmic reticulum vesicles is dependent on Ca2+ and is modulated by Mg2+, adenine nucleotide, and calmodulin. J Biol Chem. 1987; 262: 3065-3073.
34. Fukumoto GH, Lamp ST, Motter C, Bridge JH, Garfinkel A, Goldhaber JI. Metabolic inhibition alters subcellular calcium release patterns in rat ventricular myocytes: implications for defective excitation-contraction coupling during cardiac ischemia and failure. Circ Res. 2005; 96: 551-557.
35. Clusin WT. Mechanisms of calcium transient and action potential alternans in cardiac cells and tissues. Am J Physiol Heart Circ Physiol. 2008; 294:H1-H10.
36. Qian YW, Clusin WT, Lin SF, Han J, Sung RJ. Spatial heterogeneity of calcium transient alternans during the early phase of myocardial ischemia in the blood-perfused rabbit heart. Circulation. 2001; 104: 2082-2087.
37. Lee HC, Mohabir R, Smith N, Franz MR, Clusin WT. Effect of ischemia on calcium-dependent fluorescence transients in rabbit hearts containing indo 1: correlation with monophasic action potentials and contraction. Circulation. 1988; 78:1047-1059.
38. Dilly SG, Lab MJ. Electrophysiological alternans and restitution during acute regional ischaemia in myocardium of anaesthetized pig. J Physiol. 1988; 402:315-333.
39. Gao Z, Barth AS, DiSilvestre D, Akar FG, Tian Y, Tanskanen A, Kass DA, Winslow RL, Tomaselli GF. Key pathways associated with heart failure development revealed by gene networks correlated with cardiac remodeling. Physiol Genomics. 2008; 35:222-230.
40. Scarpulla RC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev. 2008; 88:611- 638.
41. Watanabe A, Arai M, Ohyama Y, Kurabayashi M. Mitochondrial transcription factors Tfam and Tfb2m regulate the SERCA2 gene transcription: a novel mechanism of the coordinate regulation of energy production and expenditure. Circulation. 2008; 118:S-517.
42. Ogbaghebriel A, Shrier A. Inhibition of metabolism abolishes transient outward current in rabbit atrial myocytes. Am J Physiol. 1994; 266: H182-H190.
43. Aksnes TA, Schmieder RE, Kjeldsen SE, Ghani S, Hua TA, Julius S. Impact of new-onset diabetes mellitus on development of AF and heart failure in high-risk hypertension (from the VALUE Trial). Am J Cardiol. 2008; 101:634-638.
44. Xu Z, Patel KP, Lou MF, Rozanski GJ. Up-regulation of K(-) channels in diabetic rat ventricular myocytes by insulin and glutathione. Cardiovasc Res. 2002; 53:80-88. (Pubitemid 34020768)
45. Xu Z, Patel KP, Rozanski GJ. Metabolic basis of decreased transient outward K+ current in ventricular myocytes from diabetic rats. Am J Physiol. 1996; 271:H2190-H2196.
46. Shimoni Y, Firek L, Severson D, Giles W. Short-term diabetes alters K+ currents in rat ventricular myocytes. Circ Res. 1994; 74:620-628.
47. Marionneau C, Aimond F, Brunet S, Niwa N, Finck B, Kelly DP, Nerbonne JM. PPARalpha-mediated remodeling of repolarizing voltage-gated K+ (Kv) channels in a mouse model of metabolic cardiomyopathy. J Mol Cell Cardiol. 2008; 44:1002-1015.
48. Xu Z, Rozanski GJ. K+ current inhibition by amphiphilic fatty acid metabolites in rat ventricular myocytes. Am J Physiol. 1998; 275: C1660-1667.
49. Shimoni Y, Liu XF. Gender differences in ANG II levels and action on multiple K+ current modulation pathways in diabetic rats. Am J Physiol Heart Circ Physiol. 2004; 287:H311-H319.
50. Lengyel C, Virag L, Biro T, Jost N, Magyar J, Biliczki P, Kocsis E, Skoumal R, Nanasi PP, Toth M, Kecskemeti V, Papp JG, Varro A. Diabetes mellitus attenuates the repolarization reserve in mammalian heart. Cardiovasc Res. 2007; 73:512-520.
51. Inagaki N, Gonoi T, Clement JP, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L, Seino S, Bryan J. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science. 1995; 270: 1166-1170.
52. Noma A. ATP-regulated K+ channels in cardiac muscle. Nature. 1983; 305:147-148.
53. Zingman LV, Alekseev AE, Hodgson-Zingman DM, Terzic A. ATPsensitive potassium channels: metabolic sensing and cardioprotection. J Appl Physiol. 2007; 103:1888 -1893.
54. O'Rourke B, Ramza BM, Marban E. Oscillations of membrane current and excitability driven by metabolic oscillations in heart cells. Science. 1994; 265:962-966.
55. Weiss JN, Lamp ST. Glycolysis preferentially inhibits ATP-sensitive K+ channels in isolated guinea pig cardiac myocytes. Science. 1987; 238:67- 69.
56. Dhar-Chowdhury P, Harrell MD, Han SY, Jankowska D, Parachuru L, Morrissey A, Srivastava S, Liu W, Malester B, Yoshida H, Coetzee WA. The glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase, triose-phosphate isomerase, and pyruvate kinase are components of the K(ATP) channel macromolecular complex and regulate its function. J Biol Chem. 2005; 280:38464 -38470.
57. Jovanovic S, Du Q, Crawford RM, Budas GR, Stagljar I, Jovanovic A. Glyceraldehyde 3-phosphate dehydrogenase serves as an accessory protein of the cardiac sarcolemmal K(ATP) channel. EMBO Rep. 2005; 6:848-852.
58. Jovanovic S, Jovanovic A. High glucose regulates the activity of cardiac sarcolemmal ATP-sensitive K+ channels via 1, 3-bisphosphoglycerate: a novel link between cardiac membrane excitability and glucose metabolism. Diabetes. 2005; 54:383-393.
59. Shimoni Y, Light PE, French RJ. Altered ATP sensitivity of ATP-dependent K+ channels in diabetic rat hearts. Am J Physiol. 1998; 275: E568-E576.
60. Smith JM, Wahler GM. ATP-sensitive potassium channels are altered in ventricular myocytes from diabetic rats. Mol Cell Biochem. 1996; 158: 43-51.
61. Li RA, Leppo M, Miki T, Seino S, Marban E. Molecular basis of electrocardiographic ST-segment elevation. Circ Res. 2000; 87: 837-839.
62. Zingman LV, Hodgson DM, Bast PH, Kane GC, Perez-Terzic C, Gumina RJ, Pucar D, Bienengraeber M, Dzeja PP, Miki T, Seino S, Alekseev AE, Terzic A. Kir6.2 is required for adaptation to stress. Proc Natl Acad Sci U S A. 2002; 99:13278 -13283.
63. Bauer A, Becker R, Dreyhaupt J, Voss F, Kraft P, Kelemen K, Senges- Becker JC, Katus HA, Schoels W. Role of KATP channels in repetitive induction of ventricular fibrillation. Europace. 2007; 9:154 -161.
64. Billman GE, Avendano CE, Halliwill JR, Burroughs JM. The effects of the ATP-dependent potassium channel antagonist, glyburide, on coronary blood flow and susceptibility to ventricular fibrillation in unanesthetized dogs. J Cardiovasc Pharmacol. 1993; 21:197-204.
65. Marin-Garcia J, Goldenthal MJ. Heart mitochondria signaling pathways: appraisal of an emerging field. J Mol Med. 2004; 82:565-578.
66. Turrens JF, Boveris A. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem J. 1980; 191: 421-427.
67. Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ. Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem. 2003; 278:36027-36031.
68. Corbucci GG, Perrino C, Donato G, Ricchi A, Lettieri B, Troncone G, Indolfi C, Chiariello M, Avvedimento EV. Transient and reversible deoxyribonucleic acid damage in human left ventricle under controlled ischemia and reperfusion. J Am Coll Cardiol. 2004; 43:1992-1999.
69. Zorov DB, Filburn CR, Klotz LO, Zweier JL, Sollott SJ. Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes. J Exp Med. 2000; 192:1001-1014.
70. Aon MA, Cortassa S, Marban E, O'Rourke B. Synchronized whole cell oscillations in mitochondrial metabolism triggered by a local release of reactive oxygen species in cardiac myocytes. J Biol Chem. 2003; 278: 44735-44744.
71. Aon MA, Cortassa S, O'Rourke B. Percolation and criticality in a mitochondrial network. Proc Natl Acad Sci U S A. 2004; 101: 4447-4452.
72. Cortassa S, Aon MA, Winslow RL, O'Rourke B. A mitochondrial oscillator dependent on reactive oxygen species. Biophys J. 2004; 87: 2060-2073.
73. Brady NR, Hamacher-Brady A, Westerhoff HV, Gottlieb RA. A wave of reactive oxygen species (ROS)-induced ROS release in a sea of excitable mitochondria. Antioxid Redox Signal. 2006; 8:1651-1665.
74. Aon MA, Cortassa S, Akar FG, O'Rourke B. Mitochondrial criticality: a new concept at the turning point of life or death. Biochim Biophys Acta. 2006; 1762:232-240.
75. Aon MA, Cortassa S, O'Rourke B. The fundamental organization of cardiac mitochondria as a network of coupled oscillators. Biophys J. 2006; 91:4317- 4327.
76. Akar FG, Aon MA, Tomaselli GF, O'Rourke B. The mitochondrial origin of postischemic arrhythmias. J Clin Invest. 2005; 115:3527-3535.
77. Cheung PC, Salt IP, Davies SP, Hardie DG, Carling D. Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding. Biochem J. 2000; 346 Pt 3:659-669.
78. Davies SP, Hawley SA, Woods A, Carling D, Haystead TA, Hardie DG. Purification of the AMP-activated protein kinase on ATP-gammasepharose and analysis of its subunit structure. Eur J Biochem. 1994; 223:351-357.
79. Hardie DG, Carling D. The AMP-activated protein kinase: fuel gauge of the mammalian cell? Eur J Biochem. 1997; 246:259 -273.
80. Hardie DG. AM. P-activated protein kinase: the guardian of cardiac energy status. J Clin Invest. 2004; 114:465- 468.
81. Pelletier A, Joly E, Prentki M, Coderre L. Adenosine 5′- monophosphate-activated protein kinase and p38 mitogen-activated protein kinase participate in the stimulation of glucose uptake by dinitrophenol in adult cardiomyocytes. Endocrinology. 2005; 146: 2285-2294.
82. Davies JK, Wells DJ, Liu K, Whitrow HR, Daniel TD, Grignani R, Lygate CA, Schneider JE, Noel G, Watkins H, Carling D. Characterization of the role of gamma2 R531G mutation in AMP-activated protein kinase in cardiac hypertrophy and Wolff-Parkinson-White syndrome. Am J Physiol Heart Circ Physiol. 2006; 290:H1942-H1951.
83. Sidhu JS, Rajawat YS, Rami TG, Gollob MH, Wang Z, Yuan R, Marian AJ, DeMayo FJ, Weilbacher D, Taffet GE, Davies JK, Carling D, Khoury DS, Roberts R. Transgenic mouse model of ventricular preexcitation and atrioventricular reentrant tachycardia induced by an AMP-activated protein kinase loss-of-function mutation responsible for Wolff- Parkinson-White syndrome. Circulation. 2005; 111:21-29.
84. Zou L, Shen M, Arad M, He H, Lofgren B, Ingwall JS, Seidman CE, Seidman JG, Tian R. N488I mutation of the gamma2-subunit results in bidirectional changes in AMP-activated protein kinase activity. Circ Res. 2005; 97:323-328.
85. Arad M, Benson DW, Perez-Atayde AR, McKenna WJ, Sparks EA, Kanter RJ, McGarry K, Seidman JG, Seidman CE. Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest. 2002; 109:357-362.
86. Gollob MH, Seger JJ, Gollob TN, Tapscott T, Gonzales O, Bachinski L, Roberts R. Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation. 2001; 104:3030 -3033.
87. Light PE, Wallace CH, Dyck JR. Constitutively active adenosine monophosphate-activated protein kinase regulates voltage-gated sodium channels in ventricular myocytes. Circulation. 2003; 107:1962-1965.
88. Li J, Hu X, Selvakumar P, Russell RR III, Cushman SW, Holman GD, Young LH. Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle. Am J Physiol Endocrinol Metab. 2004; 287:E834 -E841.
89. Bonnet D, Martin D, Pascale De L, Villain E, Jouvet P, Rabier D, Brivet M, Saudubray JM. Arrhythmias and conduction defects as presenting symptoms of fatty acid oxidation disorders in children. Circulation. 1999; 100:2248 -2253.
90. Cha YM, Dzeja PP, Shen WK, Jahangir A, Hart CY, Terzic A, Redfield MM. Failing atrial myocardium: energetic deficits accompany structural remodeling and electrical instability. Am J Physiol Heart Circ Physiol. 2003; 284:H1313-H1320.
91. Mayr M, Yusuf S, Weir G, Chung YL, Mayr U, Yin X, Ladroue C, Madhu B, Roberts N, De Souza A, Fredericks S, Stubbs M, Griffiths JR, Jahangiri M, Xu Q, Camm AJ. Combined metabolomic and proteomic analysis of human atrial fibrillation. J Am Coll Cardiol. 2008; 51: 585-594.
92. Barth AS, Merk S, Arnoldi E, Zwermann L, Kloos P, Gebauer M, Steinmeyer K, Bleich M, Kaab S, Hinterseer M, Kartmann H, Kreuzer E, Dugas M, Steinbeck G, Nabauer M. Reprogramming of the human atrial transcriptome in permanent atrial fibrillation: expression of a ventricular-like genomic signature. Circ Res. 2005; 96:1022-1029.
93. Ausma J, Coumans WA, Duimel H, Van der Vusse GJ, Allessie MA, Borgers M. Atrial high energy phosphate content and mitochondrial enzyme activity during chronic atrial fibrillation. Cardiovasc Res. 2000; 47:788 -796.
94. Barbey O, Pierre S, Duran MJ, Sennoune S, Levy S, Maixent JM. Specific up-regulation of mitochondrial F0F1-ATPase activity after short episodes of atrial fibrillation in sheep. J Cardiovasc Electrophysiol. 2000; 11:432-438.
95. Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH, Arensberg D, Baker A, Friedman L, Greene HL. Mortality and morbidity in patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression Trial. N Engl J Med. 1991; 324: 781-788.
96. Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF, Pitt B, Pratt CM, Schwartz PJ, Veltri EP. Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction: the SWORD Investigators: Survival With Oral d-Sotalol. Lancet. 1996; 348:7-12.
97. Freudenberger RS, Wilson AC, Kostis JB. Comparison of rate versus rhythm control for atrial fibrillation in patients with left ventricular dysfunction (from the AFFIRM Study). Am J Cardiol. 2007; 100:247-252.
98. Van Gelder, IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, Said SA, Darmanata JI, Timmermans AJ, Tijssen JG, Crijns HJ. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002; 347: 1834-1840.
99. Coplen SE, Antman EM, Berlin JA, Hewitt P, Chalmers TC. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion: a meta-analysis of randomized control trials. Circulation. 1990; 82:1106 -1116.
100. Abozguia K, Clarke K, Lee L, Frenneaux M. Modification of myocardial substrate use as a therapy for heart failure. Nat Clin Pract Cardiovasc Med. 2006; 3:490-498.
101. Brown DA, Aon MA, Akar FG, Liu T, Sorarrain N, O'Rourke B. Effects of 4′-chlorodiazepam on cellular excitation-contraction coupling and ischaemia-reperfusion injury in rabbit heart. Cardiovasc Res. 2008; 79: 141-149.
102. Jupiter DC, VanBuren V. A visual data mining tool that facilitates reconstruction of transcription regulatory networks. PLoS ONE. 2008; 3:e1717.