Isolated heart models for studying cardiac electrophysiology: a historical perspective and recent advances

References

1. Hearse DJ, Sutherland FJ. Experimental models for the study of cardiovascular function and disease. Pharmacol Res 2000;41:597–603.10.1006/phrs.1999.0651Search in Google Scholar PubMed

2. Fink M, Noble D. Pharmacodynamic effects in the cardiovascular system: the modeller's view. Basic Clin Pharmacol Toxicol 2010;106:243–9.10.1111/j.1742-7843.2009.00534.xSearch in Google Scholar PubMed

3. Hu Z, Chen Z, Wang Y, Jiang J, Tse G, Xu W, et al. Effects of granulocyte colony-stimulating factor on rabbit carotid and swine heart models of chronic obliterative arterial disease. Mol Med Rep 2016.Search in Google Scholar

4. Szel T, Koncz I, Antzelevitch C. Cellular mechanisms underlying the effects of milrinone and cilostazol to suppress arrhythmogenesis associated with Brugada syndrome. Heart Rhythm 2013;10:1720–7.10.1016/j.hrthm.2013.07.047Search in Google Scholar PubMed PubMed Central

5. Palatinus JA, Gourdie RG. Diabetes increases cryoinjury size with associated effects on Cx43 gap junction function and phosphorylation in the mouse heart. J Diabetes Res 2016;2016:8789617.10.1155/2016/8789617Search in Google Scholar PubMed PubMed Central

6. George SA, Sciuto KJ, Lin J, Salama ME, Keener JP, Gourdie RG, et al. Extracellular sodium and potassium levels modulate cardiac conduction in mice heterozygous null for the Connexin43 gene. Pflugers Arch 2015;467:2287–97.10.1007/s00424-015-1698-0Search in Google Scholar PubMed PubMed Central

7. Veeraraghavan R, Gourdie RG, Poelzing S. Mechanisms of cardiac conduction: a history of revisions. Am J Physiol Heart Circ Physiol 2014;306:H619–27.10.1152/ajpheart.00760.2013Search in Google Scholar PubMed PubMed Central

8. Gourdie RG, Green CR, Severs NJ, Anderson RH, Thompson RP. Evidence for a distinct gap-junctional phenotype in ventricular conduction tissues of the developing and mature avian heart. Circ Res 1993;72:278–89.10.1161/01.RES.72.2.278Search in Google Scholar

9. Moses Hr, Dorsey ER, Matheson DH, Thier S. Financial anatomy of biomedical research. J Am Med Assoc 2005;294:1333–42.10.1001/jama.294.11.1333Search in Google Scholar PubMed

10. Hall BH. The financing of research and development. Oxf Rev Econ Policy 2002;18:35–51.10.3386/w8773Search in Google Scholar

11. Paton W. Man and mouse: animals in medical research. Oxford: Oxford University Press, 1984.Search in Google Scholar

12. Tse G, Wong ST, Tse V, Yeo JM. Depolarization vs. repolarization: what is the mechanism of ventricular arrhythmogenesis underlying sodium channel haploinsufficiency in mouse hearts? Acta Physiol (Oxf) 2016;218:234–5.10.1111/apha.12694Search in Google Scholar PubMed

13. Tse G, Wong ST, Tse V, Yeo JM. Variability in local action potential durations, dispersion of repolarization and wavelength restitution in aged wild-type and Scn5a+/– mouse hearts modelling human Brugada syndrome. J Geriatr Cardiol 2016.Search in Google Scholar

14. Tse G, Wong ST, Tse V, Yeo JM. Determination of action potential wavelength restitution in Scn5a+/– mouse hearts modelling human Brugada syndrome. J Geriatr Cardiol 2016.Search in Google Scholar

15. Tse G, Li KH, Laxton V, Chan YW, Keung W, Li RA, et al. Electrophysiological mechanisms of Brugada syndrome: insights from pre-clinical and clinical studies. Front Physiol 2016;7:467.10.3389/fphys.2016.00467Search in Google Scholar PubMed PubMed Central

16. Xu A, Huang Y. A Tireless Giant in Vascular Research. J Cardiovasc Pharmacol 2016;67:359–60.10.1097/FJC.0000000000000389Search in Google Scholar PubMed

17. Tse G, Yan BP, Chan YW, Tian XY, Huang Y. Reactive oxygen species, endoplasmic reticulum stress and mitochondrial dysfunction: the link with cardiac arrhythmogenesis. Front Physiol 2016;7:313.10.3389/fphys.2016.00313Search in Google Scholar PubMed PubMed Central

18. Zhang H, Liu J, Qu D, Wang L, Luo JY, Lau CW, et al. Inhibition of miR-200c restores endothelial function in diabetic mice through suppression of COX-2. Diabetes 2016;65:1196–207.10.2337/db15-1067Search in Google Scholar PubMed

19. Zheng H, Pu SY, Fan XF, Li XS, Zhang Y, Yuan J, et al. Treatment with angiotensin-(1-9) alleviates the cardiomyopathy in streptozotocin-induced diabetic rats. Biochem Pharmacol 2015;95:38–45.10.1016/j.bcp.2015.03.009Search in Google Scholar PubMed

20. Zhang Y, Liu J, Luo JY, Tian XY, Cheang WS, Xu J, et al. Upregulation of angiotensin (1-7)-mediated signaling preserves endothelial function through reducing oxidative stress in diabetes. Antioxid Redox Signal 2015;23:880–92.10.1089/ars.2014.6070Search in Google Scholar PubMed PubMed Central

21. Murugan D, Lau YS, Lau WC, Mustafa MR, Huang Y. Angiotensin 1-7 protects against angiotensin II-induced endoplasmic reticulum stress and endothelial dysfunction via Mas receptor. PLoS One 2015;10:e0145413.10.1371/journal.pone.0145413Search in Google Scholar PubMed PubMed Central

22. Cheang WS, Tian XY, Wong WT, Lau CW, Lee SS, Chen ZY, et al. Metformin protects endothelial function in diet-induced obese mice by inhibition of endoplasmic reticulum stress through 5' adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor delta pathway. Arterioscler Thromb Vasc Biol 2014;34:830–6.10.1161/ATVBAHA.113.301938Search in Google Scholar PubMed

23. London B. Mouse models of cardiac arrhythmias. In: Saunders JH, editor. Cardiac electrophysiology: from cell to bedside, 4th ed. Philadelphia, PA, 2004:433–43.10.1016/B0-7216-0323-8/50051-8Search in Google Scholar

24. London B. Cardiac arrhythmias: from (transgenic) mice to men. J Cardiovasc Electrophysiol 2001;12:1089–91.10.1046/j.1540-8167.2001.01089.xSearch in Google Scholar PubMed

25. Baker LC, London B, Choi BR, Koren G, Salama G. Enhanced dispersion of repolarization and refractoriness in transgenic mouse hearts promotes reentrant ventricular tachycardia. Circ Res 2000;86:396–407.10.1161/01.RES.86.4.396Search in Google Scholar

26. Wang L, Swirp S, Duff H. Age-dependent response of the electrocardiogram to K(+) channel blockers in mice. Am J Physiol Cell Physiol 2000;278:C73–80.10.1152/ajpcell.2000.278.1.C73Search in Google Scholar

27. Nerbonne JM. Molecular basis of functional voltage-gated K+ channel diversity in the mammalian myocardium. J Physiol 2000;525:285–98.10.1111/j.1469-7793.2000.t01-1-00285.xSearch in Google Scholar

28. Bers DM. Cardiac excitation-contraction coupling. Nature 2002;415:198–205.10.1016/B978-0-12-378630-2.00221-8Search in Google Scholar

29. Bers DM, Despa S. Na/K-ATPase – an integral player in the adrenergic fight-or-flight response. Trends Cardiovasc Med 2009;19:111–8.10.1016/j.tcm.2009.07.001Search in Google Scholar

30. Kettlewell S, Burton FL, Smith GL, Workman AJ. Chronic myocardial infarction promotes atrial action potential alternans, afterdepolarizations, and fibrillation. Cardiovasc Res 2013;99:215–24.10.1093/cvr/cvt087Search in Google Scholar

31. Workman AJ, Kane KA, Rankin AC. Rate-dependency of action potential duration and refractoriness in isolated myocytes from the rabbit AV node and atrium. J Mol Cell Cardiol 2000;32:1525–37.10.1006/jmcc.2000.1186Search in Google Scholar

32. Workman AJ, Kane KA, Rankin AC. Ionic basis of a differential effect of adenosine on refractoriness in rabbit AV nodal and atrial isolated myocytes. Cardiovasc Res 1999;43:974–84.10.1016/S0008-6363(99)00166-2Search in Google Scholar

33. Workman AJ, Marshall GE, Rankin AC, Smith GL, Dempster J. Transient outward K+ current reduction prolongs action potentials and promotes afterdepolarisations: a dynamic-clamp study in human and rabbit cardiac atrial myocytes. J Physiol 2012;590:4289–305.10.1113/jphysiol.2012.235986Search in Google Scholar PubMed PubMed Central

34. Hsieh YC, Lin SF, Huang JL, Hung CY, Lin JC, Liao YC, et al. Moderate hypothermia (33C) decreases the susceptibility to pacing-induced ventricular fibrillation compared with severe hypothermia (30C) by attenuating spatially discordant alternans in isolated rabbit hearts. Acta Cardiol Sin 2014;30:455–65.Search in Google Scholar

35. Osadchii OE. Impact of hypokalemia on electromechanical window, excitation wavelength and repolarization gradients in guinea-pig and rabbit hearts. PLoS One 2014;9:e105599.10.1371/journal.pone.0105599Search in Google Scholar PubMed PubMed Central

36. Ng GA, Cobbe SM, Smith GL. Non-uniform prolongation of intracellular Ca2+ transients recorded from the epicardial surface of isolated hearts from rabbits with heart failure. Cardiovasc Res 1998;37:489–502.10.1016/S0008-6363(97)00255-1Search in Google Scholar

37. Chang C-J, Cheng C-C, Chen Y-C, Kao Y-H, Chen S-A, Chen Y-J. Gap junction modifiers regulate electrical activities of the sinoatrial node and pulmonary vein: therapeutic implications in atrial arrhythmogenesis. Int J Cardiol 2016;221:529–36.10.1016/j.ijcard.2016.07.027Search in Google Scholar PubMed

38. Osadchii OE. Effects of ventricular pacing protocol on electrical restitution assessments in guinea-pig heart. Exp Physiol 2012;97:807–21.10.1113/expphysiol.2012.065219Search in Google Scholar PubMed

39. Osadchii OE. Flecainide attenuates rate adaptation of ventricular repolarization in guinea-pig heart. Scand Cardiovasc J 2016;50:28–35.10.3109/14017431.2015.1099721Search in Google Scholar PubMed

40. Osadchii OE. Impaired epicardial activation-repolarization coupling contributes to the proarrhythmic effects of hypokalaemia and dofetilide in guinea pig ventricles. Acta Physiol (Oxf) 2014;211:48–60.10.1111/apha.12259Search in Google Scholar PubMed

41. Osadchii OE. Flecainide-induced proarrhythmia is attributed to abnormal changes in repolarization and refractoriness in perfused guinea-pig heart. J Cardiovasc Pharmacol 2012;60:456–66.10.1097/FJC.0b013e31826b86cfSearch in Google Scholar PubMed

42. Osadchii OE. Dofetilide promotes repolarization abnormalities in perfused Guinea-pig heart. Cardiovasc Drugs Ther 2012;26:489–500.10.1007/s10557-012-6405-1Search in Google Scholar PubMed

43. Osadchii OE. Quinidine elicits proarrhythmic changes in ventricular repolarization and refractoriness in guinea-pig. Can J Physiol Pharmacol 2013;91:306–15.10.1139/cjpp-2012-0379Search in Google Scholar PubMed

44. Osadchii OE, Bentzen BH, Olesen SP. Chamber-specific effects of hypokalaemia on ventricular arrhythmogenicity in isolated, perfused guinea-pig heart. Exp Physiol 2009;94:434–46.10.1113/expphysiol.2008.045567Search in Google Scholar PubMed

45. Osadchii OE, Olesen SP. Electrophysiological determinants of hypokalaemia-induced arrhythmogenicity in the guinea-pig heart. Acta Physiol (Oxf) 2009;197:273–87.10.1111/j.1748-1716.2009.02028.xSearch in Google Scholar PubMed

46. Brunner M, Peng X, Liu GX, Ren XQ, Ziv O, Choi BR, et al. Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome. J Clin Invest 2008;118:2246–59.10.1172/JCI33578Search in Google Scholar PubMed PubMed Central

47. Hondeghem LM. Disturbances of cardiac wavelength and repolarization precede Torsade de Pointes and ventricular fibrillation in Langendorff perfused rabbit hearts. Prog Biophys Mol Biol 2016;121:3–10.10.1016/j.pbiomolbio.2016.03.004Search in Google Scholar PubMed

48. Lu HR, Yan G-X, Gallacher DJ. A new biomarker – index of Cardiac Electrophysiological Balance (iCEB) – plays an important role in drug-induced cardiac arrhythmias: beyond QT-prolongation and Torsades de Pointes (TdPs). J Pharmacol Toxicol Methods 2013;68:250–9.10.1016/j.vascn.2013.01.003Search in Google Scholar PubMed

49. Milberg P, Reinsch N, Osada N, Wasmer K, Monnig G, Stypmann J, et al. Verapamil prevents torsade de pointes by reduction of transmural dispersion of repolarization and suppression of early afterdepolarizations in an intact heart model of LQT3. Basic Res Cardiol 2005;100:365–71.10.1007/s00395-005-0533-8Search in Google Scholar PubMed

50. Tse G, Ali A, Prasad SK, Vassiliou V, Raphael CE. Atypical case of post-partum cardiomyopathy: an overlap syndrome with arrhythmogenic right ventricular cardiomyopathy? BJR Case Rep 2015;1:20150182.10.1259/bjrcr.20150182Search in Google Scholar PubMed PubMed Central

51. Tse G, Ali A, Alpendurada F, Prasad S, Raphael CE, Vassiliou V. Tuberculous constrictive pericarditis. Res Cardiovasc Med 2015;4:e29614.10.5812/cardiovascmed.29614Search in Google Scholar PubMed PubMed Central

52. Vassiliou V, Chin C, Perperoglou A, Tse G, Ali A, Raphael C, et al. 93 ejection fraction by cardiovascular magnetic resonance predicts adverse outcomes post aortic valve replacement. Heart 2014;100:A53–4.10.1136/heartjnl-2014-306118.93Search in Google Scholar

53. Vaillant F, Magat J, Bour P, Naulin J, Benoist D, Loyer V, et al. Magnetic resonance-compatible model of isolated working heart from large animal for multimodal assessment of cardiac function, electrophysiology and metabolism. Am J Physiol Heart Circ Physiol 2016;310:H1371–80.10.1152/ajpheart.00825.2015Search in Google Scholar PubMed

54. Elkins RC. Is tissue-engineered heart valve replacement clinically applicable? Curr Cardiol Rep 2003;5:125–8.10.1007/s11886-003-0079-zSearch in Google Scholar PubMed

55. Rivard AL, Suwan PT, Imaninaini K, Gallegos RP, Bianco RW. Development of a sheep model of atrial fibrillation for preclinical prosthetic valve testing. J Heart Valve Dis 2007;16:314–23.Search in Google Scholar

56. Gallegos RP, Nockel PJ, Rivard AL, Bianco RW. The current state of in-vivo pre-clinical animal models for heart valve evaluation. J Heart Valve Dis 2005;14:423–32.Search in Google Scholar

57. Stengl M. Experimental models of spontaneous ventricular arrhythmias and of sudden cardiac death. Physiol Res 2010;59:S25–31.10.33549/physiolres.932001Search in Google Scholar PubMed

58. Chen Z, Sun B, Tse G, Jiang J, Xu W. Reversibility of both sinus node dysfunction and reduced HCN4 mRNA expression level in an atrial tachycardia pacing model of tachycardia-bradycardia syndrome in rabbit hearts. Int J Clin Exp Pathol 2016;9:8526–8531.Search in Google Scholar

59. Workman AJ, MacKenzie I, Northover BJ. Do KATP channels open as a prominent and early feature during ischaemia in the Langendorff-perfused rat heart? Basic Res Cardiol 2000;95:250–60.10.1007/s003950050188Search in Google Scholar

60. Workman AJ, MacKenzie I, Northover BJ. A K(ATP) channel opener inhibited myocardial reperfusion action potential shortening and arrhythmias. Eur J Pharmacol 2001;419:73–83.10.1016/S0014-2999(01)00972-4Search in Google Scholar

61. Hagendorff A, Schumacher B, Kirchhoff S, Luderitz B, Willecke K. Conduction disturbances and increased atrial vulnerability in Connexin40-deficient mice analyzed by transesophageal stimulation. Circulation 1999;99:1508–15.10.1161/01.CIR.99.11.1508Search in Google Scholar

62. Sun B, Qi X, Jiang J. Heptanol decreases the incidence of ischemia-induced ventricular arrhythmias through altering electrophysiological properties and connexin 43 in rat hearts. Biomed Rep 2014;2:349–53.10.3892/br.2014.247Search in Google Scholar

63. Shi S, Liu T, Wang D, Zhang Y, Liang J, Yang B, et al. Activation of N-methyl-d-aspartate receptors reduces heart rate variability and facilitates atrial fibrillation in rats. Europace 2016 [ahead of print: pii: euw086].10.1093/europace/euw086Search in Google Scholar

64. Cyon E. Über den einfluss der temperaturänderungen auf zahl, dauer und stärke der herzschläge. Berichte über die verhandlungen der königlich sächsischen gesellschaft der wissenschaften zu Leipzig. Mathematisch-Physische Classe 1866;18:256–306.Search in Google Scholar

65. Langendorff O. Untersuchungen am überlebenden Säugetierherzen. Pflug Archiv 1898;61:291–332.10.1007/BF01812150Search in Google Scholar

66. Taegtmeyer H. One hundred years ago: Oscar Langendorff and the birth of cardiac metabolism. Can J Cardiol 1995;11:1030–35.Search in Google Scholar

67. Zimmer HG. The isolated perfused heart and its pioneers. News Physiol Sci 1998;13:203–10.10.1152/physiologyonline.1998.13.4.203Search in Google Scholar

68. Skrzypiec-Spring M, Grotthus B, Szelag A, Schulz R. Isolated heart perfusion according to Langendorff---still viable in the new millennium. J Pharmacol Toxicol Methods 2007;55:113–26.10.1016/j.vascn.2006.05.006Search in Google Scholar

69. Wiggers CJ. The innervation of the coronary vessels. Am J Physiol 1909;24:391–405.10.1152/ajplegacy.1909.24.4.391Search in Google Scholar

70. Broadley KJ. The Langendorff heart preparation—reappraisal of its role as a research and teaching model for coronary vasoactive drugs. J Pharmacol Methods 1979;2:143–56.10.1016/0160-5402(79)90038-XSearch in Google Scholar

71. Katz G, Paine WG, Tiller PM. A new method for coronary perfusion of the mammalian heart. Arch Int Pharmacodyn 1939;61:109–12.Search in Google Scholar

72. Broadley KJ. An analysis of the coronary vascular responses to catecholamines, using a modified Langendorff heart preparation. Br J Pharmacol 1970;40:617–29.10.1111/j.1476-5381.1970.tb10642.xSearch in Google Scholar

73. Choy L, Yeo JM, Tse V, Chan SP, Tse G. Cardiac disease and arrhythmogenesis: mechanistic insights from mouse models. Int J Cardiol Heart Vasc 2016;12:1–10.10.1016/j.ijcha.2016.05.005Search in Google Scholar

74. Tse G, Tse V, Yeo JM. Ventricular anti-arrhythmic effects of heptanol in hypokalaemic, Langendorff-perfused mouse hearts. Biomed Rep 2016;4:313–24.10.3892/br.2016.577Search in Google Scholar

75. Tse G, Lai ET, Lee AP, Yan BP, Wong SH. Electrophysiological mechanisms of gastrointestinal arrhythmogenesis: lessons from the heart. Front Physiol 2016;7:230.10.3389/fphys.2016.00230Search in Google Scholar

76. Sutherland FJ, Shattock MJ, Baker KE, Hearse DJ. Mouse isolated perfused heart: characteristics and cautions. Clin Exp Pharmacol Physiol 2003;30:867–78.10.1046/j.1440-1681.2003.03925.xSearch in Google Scholar

77. Liao R, Podesser BK, Lim CC. The continuing evolution of the Langendorff and ejecting murine heart: new advances in cardiac phenotyping. Am J Physiol Heart Circ Physiol 2012;303:H156–67.10.1152/ajpheart.00333.2012Search in Google Scholar

78. Neely JR, Rovetto MJ, Whitmer JT, Morgan HE. Effects of ischemia on function and metabolism of the isolated working rat heart. Am J Physiol 1973;225:651–8.10.1152/ajplegacy.1973.225.3.651Search in Google Scholar

79. Neely JR, Liebermeister H, Battersby EJ, Morgan HE. Effect of pressure development on oxygen consumption by isolated rat heart. Am J Physiol 1967;212:804–14.10.1152/ajplegacy.1967.212.4.804Search in Google Scholar

80. Bateman MG, Iaizzo PA. Comparative imaging of cardiac structures and function for the optimization of transcatheter approaches for valvular and structural heart disease. Int J Cardiovasc Imaging 2011;27:1223–34.10.1007/s10554-011-9807-4Search in Google Scholar

81. Chinchoy E, Soule CL, Houlton AJ, Gallagher WJ, Hjelle MA, Laske TG, et al. Isolated four-chamber working swine heart model. Ann Thorac Surg 2000;70:1607–14.10.1016/S0003-4975(00)01977-9Search in Google Scholar

82. Martin HN, Applegrath EC. On the temperature limits of the vitality of the mammalian heart. Stud Biol Lab Johns Hopkins Univ 1890;4:275.Search in Google Scholar

83. Manuck HP, Hockman CH. Central nervous system mechanisms mediating cardiac rate and rhythm. Am Heart J 1967;74:96–109.10.1016/0002-8703(67)90047-6Search in Google Scholar

84. Gellhorn E. The significance of the state of the central autonomic nervous system for quantitative and qualitative aspects of some cardiovascular reactions. Am Heart J 1963;67:106–20.10.1016/0002-8703(64)90406-5Search in Google Scholar

85. Mason DT. The autonomic nervous system and regulation of cardiovascular performance. Anesthesiology 1968;29:670–80.10.1097/00000542-196807000-00009Search in Google Scholar PubMed

86. Wolf S. Neural mechanisms in sudden cardiac death. Trans Am Clin Climatol Assoc 1968;79:158–76.Search in Google Scholar

87. Coumel P. Cardiac arrhythmias and the autonomic nervous system. J Cardiovasc Electrophysiol 1993;4:338–55.10.1111/j.1540-8167.1993.tb01235.xSearch in Google Scholar PubMed

88. Sutherland FJ, Hearse DJ. The isolated blood and perfusion fluid perfused heart. Pharmacol Res 2000;41:613–27.10.1006/phrs.1999.0653Search in Google Scholar PubMed

89. Mantravadi R, Gabris B, Liu T, Choi BR, de Groat WC, Ng GA, et al. Autonomic nerve stimulation reverses ventricular repolarization sequence in rabbit hearts. Circ Res 2007;100:e72–80.10.1161/01.RES.0000264101.06417.33Search in Google Scholar PubMed PubMed Central

90. Ng GA, Brack KE, Coote JH. Effects of direct sympathetic and vagus nerve stimulation on the physiology of the whole heart--a novel model of isolated Langendorff perfused rabbit heart with intact dual autonomic innervation. Exp Physiol 2001;86:319–29.10.1113/eph8602146Search in Google Scholar PubMed

91. Brack KE, Coote JH, Ng GA. Interaction between direct sympathetic and vagus nerve stimulation on heart rate in the isolated rabbit heart. Exp Physiol 2004;89:128–39.10.1113/expphysiol.2003.002654Search in Google Scholar PubMed

92. Brack KE, Coote JH, Ng GA. The effect of direct autonomic nerve stimulation on left ventricular force in the isolated innervated Langendorff perfused rabbit heart. Auton Neurosci 2006;124:69–80.10.1016/j.autneu.2005.11.005Search in Google Scholar PubMed

93. Brack KE, Coote JH, Ng GA. Vagus nerve stimulation inhibits the increase in Ca2+ transient and left ventricular force caused by sympathetic nerve stimulation but has no direct effects alone--epicardial Ca2+ fluorescence studies using fura-2 AM in the isolated innervated beating rabbit heart. Exp Physiol 2010;95:80–92.10.1113/expphysiol.2009.048215Search in Google Scholar PubMed

94. Ng GA, Brack KE, Patel VH, Coote JH. Autonomic modulation of electrical restitution, alternans and ventricular fibrillation initiation in the isolated heart. Cardiovasc Res 2007;73:750–60.10.1016/j.cardiores.2006.12.001Search in Google Scholar PubMed

95. Brack KE, Patel VH, Coote JH, Ng GA. Nitric oxide mediates the vagal protective effect on ventricular fibrillation via effects on action potential duration restitution in the rabbit heart. J Physiol 2007;583:695–704.10.1113/jphysiol.2007.138461Search in Google Scholar PubMed PubMed Central

96. Ng GA, Mantravadi R, Walker WH, Ortin WG, Choi BR, de Groat W, et al. Sympathetic nerve stimulation produces spatial heterogeneities of action potential restitution. Heart Rhythm 2009;6:696–706.10.1016/j.hrthm.2009.01.035Search in Google Scholar PubMed

97. Winter J, Brack KE, Coote JH, Ng GA. Cardiac contractility modulation increases action potential duration dispersion and decreases ventricular fibrillation threshold via beta1-adrenoceptor activation in the crystalloid perfused normal rabbit heart. Int J Cardiol 2014;172:144–54.10.1016/j.ijcard.2013.12.184Search in Google Scholar PubMed PubMed Central

98. Ng GA. Vagal modulation of cardiac ventricular arrhythmia. Exp Physiol 2014;99:295–9.10.1113/expphysiol.2013.072652Search in Google Scholar PubMed

99. Valentin JP, Hoffmann P, De Clerck F, Hammond TG, Hondeghem L. Review of the predictive value of the Langendorff heart model (Screenit system) in assessing the proarrhythmic potential of drugs. J Pharmacol Toxicol Methods 2004;49:171–81.10.1016/j.vascn.2004.03.008Search in Google Scholar PubMed

100. Tse G, Yeo JM, Tse V, Sun B. Gap junction inhibition by heptanol increases ventricular arrhythmogenicity by decreasing conduction velocity without affecting repolarization properties or myocardial refractoriness in Langendorff-perfused mouse hearts. Mol Med Rep 2016;14:4069–4074.10.3892/mmr.2016.5738Search in Google Scholar PubMed PubMed Central

101. Tse G, Lai ET, Chan YW, Yeo JM, Yan BP. What is the arrhythmic substrate in viral myocarditis? Insights from clinical and animal studies. Front Physiol 2016;7:308.10.3389/fphys.2016.00308Search in Google Scholar PubMed PubMed Central

102. Tse G, Lai ET, Yeo JM, Yan BP. Electrophysiological mechanisms of Bayés syndrome: insights from clinical and mouse studies. Front Physiol 2016;7:188.10.3389/fphys.2016.00188Search in Google Scholar PubMed PubMed Central

103. Tse G, Lai ET, Tse V, Yeo JM. Molecular and electrophysiological mechanisms underlying cardiac arrhythmogenesis in diabetes mellitus. J Diabetes Res 2016:2848759.10.1155/2016/2848759Search in Google Scholar PubMed PubMed Central

104. Pye MP, Cobbe SM. Arrhythmogenesis in experimental models of heart failure: the role of increased load. Cardiovasc Res 1996;32:248–57.10.1016/0008-6363(96)00080-6Search in Google Scholar

105. Nicolson WB, McCann GP, Brown PD, Sandilands AJ, Stafford PJ, Schlindwein FS, et al. A novel surface electrocardiogram-based marker of ventricular arrhythmia risk in patients with ischemic cardiomyopathy. J Am Heart Assoc 2012;1:e001552.10.1161/xJAHA.111.001552Search in Google Scholar

106. Nicolson WB, McCann GP, Smith MI, Sandilands AJ, Stafford PJ, Schlindwein FS, et al. Prospective evaluation of two novel ECG-based restitution biomarkers for prediction of sudden cardiac death risk in ischaemic cardiomyopathy. Heart 2014;100:1878–85.10.1136/heartjnl-2014-305672Search in Google Scholar

107. Tse G. Both transmural dispersion of repolarization and transmural dispersion of refractoriness are poor predictors of arrhythmogenicity: a role for the index of Cardiac Electrophysiological Balance (QT/QRS)? J Geriatr Cardiol 2016;13:813–4.Search in Google Scholar

108. Tse G. (Tpeak-Tend)/QRS and (Tpeak-Tend)/(QT x QRS): novel markers for predicting arrhythmic risk in the Brugada syndrome. Europace 2016; pii: euw194.10.1093/europace/euw194Search in Google Scholar

109. Tse G, Yan BP. Traditional and novel electrocardiographic conduction and repolarization markers of sudden cardiac death. Europace 2016; pii: euw280.10.1093/europace/euw280Search in Google Scholar

110. Tse G. Novel conduction-repolarization indices for the stratification of arrhythmic risk. J Geriatr Cardiol 2016;13:811–812.Search in Google Scholar

111. Curtis MJ, Hancox JC, Farkas A, Wainwright CL, Stables CL, Saint DA, et al. The Lambeth Conventions (II): Guidelines for the study of animal and human ventricular and supraventricular arrhythmias. Pharmacol Ther 2013;139:213–48.10.1016/j.pharmthera.2013.04.008Search in Google Scholar

112. Krebs HA, Henseleit K. Untersuchungen ueber die Harnstoffbildung im Tierkoerper. Hoppe-Seyler's Z Physiol Chem 1932;210:33–6.10.1515/bchm2.1932.210.1-2.33Search in Google Scholar

113. Reichelt ME, Willems L, Hack BA, Peart JN, Headrick JP. Cardiac and coronary function in the Langendorff-perfused mouse heart model. Exp Physiol 2009;94:54–70.10.1113/expphysiol.2008.043554Search in Google Scholar

114. Bing RJ, Siegel A, Ungar I, Gilbert M. Studies on fat, ketone and amino acid metabolism. Am J Med 1954;16:504–15.10.1016/0002-9343(54)90365-4Search in Google Scholar

115. Belke DD, Larsen TS, Lopaschuk GD, Severson DL. Glucose and fatty acid metabolism in the isolated working mouse heart. Am J Physiol 1999;277:R1210–7.10.1152/ajpregu.1999.277.4.R1210Search in Google Scholar PubMed

116. Bell RM, Mocanu MM, Yellon DM. Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion. J Mol Cell Cardiol 2011;50:940–50.10.1016/j.yjmcc.2011.02.018Search in Google Scholar

117. Bing RJ. Some aspects of biochemistry of myocardial infarction. Cell Mol Life Sci 2001;58:351–5.10.1007/PL00000862Search in Google Scholar

118. Qiu Y, Hearse DJ. Comparison of ischemic vulnerability and responsiveness to cardioplegic protection in crystalloid-perfused versus blood-perfused hearts. J Thorac Cardiovasc Surg 1992;103:960–8.10.1016/S0022-5223(19)34921-9Search in Google Scholar

119. Armitage WJ, Pegg DE. An evaluation of colloidal solutions for normothermic perfusion of rabbit hearts: an improved perfusate containing Haemaccel. Cryobiology 1977;14:428–34.10.1016/0011-2240(77)90004-9Search in Google Scholar

120. Zausig YA, Chappell D, Becker BF, Potschka D, Busse H, Nixdorf K, et al. The impact of crystalloidal and colloidal infusion preparations on coronary vascular integrity, interstitial oedema and cardiac performance in isolated hearts. Crit Care 2013;17:R203.10.1186/cc12898Search in Google Scholar PubMed PubMed Central

121. White CW, Hasanally D, Mundt P, Li Y, Xiang B, Klein J, et al. A whole blood-based perfusate provides superior preservation of myocardial function during ex vivo heart perfusion. J Heart Lung Transplant 2015;34:113–21.10.1016/j.healun.2014.09.021Search in Google Scholar PubMed

122. Pasini E, Solfrini R, Bachetti T, Marino M, Bernocchi P, Visioli F, et al. The blood perfused isolated heart: characterization of the model. Basic Res Cardiol 1999;94:215–22.10.1007/s003950050145Search in Google Scholar PubMed