Inflammation and cardiac dysfunction during sepsis, muscular dystrophy, and myocarditis

Burns and Trauma

Volumn 1, Issue 3, 2013, Pages 109-121

  Li, Ying ^a,b   Ge, Shuping ^c   Peng, Yizhi ^a   Chen, Xiongwen ^b  

^a THIRD MILITARY MEDICAL UNIVERSITY   (China)

^b TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c DREXEL UNIVERSITY COLLEGE OF MEDICINE   (United States)

Author keywords

Burn; cardiac dysfunction; contractility; Duchenne muscular dystrophy; inflammation; sepsis

Indexed keywords

EID: 84921435640     PISSN: None     EISSN: 23213876     Source Type: Journal    
DOI: 10.4103/2321-3868.123072     Document Type: Review

References (121)

1. Rendon JL, Choudhry MA. Th17 cells: Critical mediators of host responses to burn injury and sepsis. J Leukoc Biol 2012;92:529-38.
2. McEvoy C, Kollef MH. Determinants of hospital mortality among patients with sepsis or septic shock receiving appropriate antibiotic treatment. Curr Infect Dis Rep 2013;15:400-6.
3. Xie B, Xiao SC, Peng XD, Zhu SH, Lv KY, Li HY, et al. Epidemiology and outcome analysis of severe extensive burns: A 12-year summary of 103 cases in a burn center in China. J Burn Care Res 2012;33:e127-32.
4. Avlas O, Fallach R, Shainberg A, Porat E, Hochhauser E. Toll-like receptor 4 stimulation initiates an inflammatory response that decreases cardiomyocyte contractility. Antioxid Redox Signal 2011;15:1895-909.
5. Freigang S, Ampenberger F, Weiss A, Kanneganti TD, Iwakura Y, Hersberger M, et al. Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1alpha and sterile vascular inflammation in atherosclerosis. Nat Immunol. 2013;14:1045-53.
6. Zanotti-Cavazzoni SL, Hollenberg SM. Cardiac dysfunction in severe sepsis and septic shock. Curr Opin Crit Care 2009;15:392-7.
7. Romero-Bermejo FJ, Ruiz-Bailen M, Gil-Cebrian J, Huertos-Ranchal MJ. Sepsis-induced cardiomyopathy. Curr Cardiol Rev 2011;7:163-83.
8. Freire MO, Van Dyke TE. Natural resolution of inflammation. Periodontol 2000. 2013;63:149-64.
9. Majo G, editor. The healing hand-man and wound in the ancient World. Cambridge: Harvard University Press; 1975.
10. Medzhitov R. Inflammation 2010: New adventures of an old flame. Cell 2010;140:771-6.
11. Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol 2011;30:16-34.
12. Peng SL. Transcription factors in autoimmune diseases. Front Biosci 2008;13:4218-40.
13. Doria A, Zen M, Bettio S, Gatto M, Bassi N, Nalotto L, et al. Autoinflammation and autoimmunity: Bridging the divide. Autoimmun Rev 2012;12:22-30.
14. Kim YW, West XZ, Byzova TV. Inflammation and oxidative stress in angiogenesis and vascular disease. J Mol Med 2013;91:323-8.
15. Xiang L, Hester RL. Cardiovascular Responses to Exercise. In: Granger DN, Granger J, editors. Jackson, MS 39216. San Rafael: Morgan and Claypool Life Sciences. 2012. 126.
16. Lahiri MK, Kannankeril PJ, Goldberger JJ. Assessment of autonomic function in cardiovascular disease: Physiological basis and prognostic implications. J Am Coll Cardiol 2008;51:1725-33.
17. Vinogradova TM, Lakatta EG. Regulation of basal and reserve cardiac pacemaker function by interactions of cAMP-mediated PKA-dependent Ca2+ cycling with surface membrane channels. J Mol Cell Cardiol 2009;47:456-74.
18. Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol 1983;245:C1-14.
19. Fabiato A. Time and calcium dependence of activation and inactivation of calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J Gen Physiol 1985;85:247-89.
20. Bers DM. Cardiac excitation-contraction coupling. Nature 2002;415:198-205.
21. Bers DM. Calcium cycling and signaling in cardiac myocytes. Annu Rev Physiol 2008;70:23-49.
22. Woo AY, Xiao RP. beta-Adrenergic receptor subtype signaling in heart: From bench to bedside. Acta Pharmacol Sin 2012;33:335-41.
23. Oestreich EA, Malik S, Goonasekera SA, Blaxall BC, Kelley GG, Dirksen RT, et al. Epac and phospholipase Cepsilon regulate Ca2+ release in the heart by activation of protein kinase Cepsilon and calcium-calmodulin kinase II. J Biol Chem 2009;284:1514-22.
24. Cazorla O, Lucas A, Poirier F, Lacampagne A, Lezoualc h F. The cAMP binding protein Epac regulates cardiac myofilament function. Proc Natl Acad Sci U S A 2009;106:14144-9.
25. Pereira L, Ruiz-Hurtado G, Morel E, Laurent AC, Metrich M, Domínguez-Rodríguez A, et al. Epac enhances excitationtranscription coupling in cardiac myocytes. J Mol Cell Cardiol 2012;52:283-91.
26. Pereira L, Cheng H, Lao DH, Na L, van Oort RJ, Brown JH, et al. Epac2 mediates cardiac beta1-Adrenergic-dependent sarcoplasmic reticulum Ca2+ leak and arrhythmia. Circulation 2013;127:913-22.
27. Ruiz-Hurtado G, Dominguez-Rodriguez A, Pereira L, Fernandez-Velasco M, Cassan C, Lezoualc h F, et al. Sustained Epac activation induces calmodulin dependent positive inotropic effect in adult cardiomyocytes. J Mol Cell Cardiol 2012;53:617-25.
28. Smrcka AV, Oestreich EA, Blaxall BC, Dirksen RT. EPAC regulation of cardiac EC coupling. J Physiol 2007;584(Pt 3):1029-31.
29. Guntheroth WG, Jacky JP, Kawabori I, Stevenson JG, Moreno AH. Left ventricular performance in endotoxin shock in dogs. Am J Physiol 1982;242:H172-6.
30. Ellrodt AG, Riedinger MS, Kimchi A, Berman DS, Maddahi J, Swan HJ, et al. Left ventricular performance in septic shock: Reversible segmental and global abnormalities. Am Heart J 1985;110:402-9.
31. Parker MM, McCarthy KE, Ognibene FP, Parrillo JE. Right ventricular dysfunction and dilatation, similar to left ventricular changes, characterize the cardiac depression of septic shock in humans. Chest 1990;97:126-31.
32. Hunter JD, Doddi M. Sepsis and the heart. Br J Anaesth 2010;104:3-11.
33. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013;39:165-228.
34. Kilbourn RG, Griffith OW, Gross SS. Pathogenetic mechanisms of septic shock. N Engl J Med 1993;329:1427-8.
35. Abraham E, Singer M. Mechanisms of sepsis-induced organ dysfunction. Crit Care Med 2007;35:2408-16.
36. Levy RJ, Deutschman CS. Cytochrome c oxidase dysfunction in sepsis. Crit Care Med 2007;35:S468-75.
37. Rabuel C, Mebazaa A. Septic shock:a heart story since the 1960s. Intensive Care Med 2006;32:799-807.
38. Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1:diagnosis, and pharmacological and psychosocial management. Lancet Neurol 2009;9:77-93.
39. Kaspar RW, Allen HD, Montanaro F. Current understanding and management of dilated cardiomyopathy in Duchenne and Becker muscular dystrophy. J Am Acad Nurse Pract 2009;21:241-9.
40. Mertens L, Ganame J, Claus P, Goemans N, Thijs D, Eyskens B, et al. Early regional myocardial dysfunction in young patients with Duchenne muscular dystrophy. J Am Soc Echocardiogr 2008;21:1049-54.
41. Ogata H, Nakatani S, Ishikawa Y, Negishi A, Kobayashi M, Ishikawa Y, et al. Myocardial strain changes in Duchenne muscular dystrophy without overt cardiomyopathy. Int J Cardiol 2007;115:190-5.
42. Mori K, Hayabuchi Y, Inoue M, Suzuki M, Sakata M, Nakagawa R, et al. Myocardial strain imaging for early detection of cardiac involvement in patients with Duchenne s progressive muscular dystrophy. Echocardiography 2007;24:598-608.
43. Takano H, Fujii Y, Yugeta N, Takeda S, Wakao Y. Assessment of left ventricular regional function in affected and carrier dogs with Duchenne muscular dystrophy using speckle tracking echocardiography. BMC Cardiovasc Disord 2011;11:23.
44. Fayssoil A. Usefulness of myocardial strain imaging in Duchenne muscular dystrophy. Int J Cardiol 2008;140:114-5.
45. Politano L, Nigro G. Treatment of dystrophinopathic cardiomyopathy: Review of the literature and personal results. Acta Myol 2012;31:24-30.
46. Allen DG, Gervasio OL, Yeung EW, Whitehead NP. Calcium and the damage pathways in muscular dystrophy. Can J Physiol Pharmacol 2010;88:83-91.
47. Allen DG, Zhang BT, Whitehead NP. Stretch-induced membrane damage in muscle: Comparison of wild-Type and mdx mice. Adv Exp Med Biol 2010;682:297-313.
48. Deconinck N, Dan B. Pathophysiology of duchenne muscular dystrophy: Current hypotheses. Pediatr Neurol 2007;36:1-7.
49. Jackson MJ, Brooke MH, Kaiser K, Edwards RH. Creatine kinase and prostaglandin E2 release from isolated Duchenne muscle. Neurology 1991;41:101-4.
50. McArdle A, Foxley A, Edwards RH, Jackson MJ. Prostaglandin metabolism in dystrophin-deficient MDX mouse muscle. Biochem Soc Trans 1991;19:177S.
51. Liu S, Li Y, Kim S, Fu Q, Parikh D, Sridhar B, et al. Phosphodiesterases coordinate cAMP propagation induced by two stimulatory G protein-coupled receptors in hearts. Proc Natl Acad Sci U S A 2012;109:6578-83.
52. Shauer A, Gotsman I, Keren A, Zwas DR, Hellman Y, Durst R, et al. Acute viral myocarditis: Current concepts in diagnosis and treatment. Isr Med Assoc J 2013;15:180-5.
53. Sagar S, Liu PP, Cooper LT Jr. Myocarditis. Lancet 2012;379:738-47.
54. D Ambrosio A, Patti G, Manzoli A, Sinagra G, Di Lenarda A, Silvestri F, et al. The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy:a review. Heart 2001;85:499-504.
55. Hufnagel G, Pankuweit S, Richter A, Schonian U, Maisch B. The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID). First epidemiological results. Herz 2000;25:279-85.
56. Punja M, Mark DG, McCoy JV, Javan R, Pines JM, Brady W, et al. Electrocardiographic manifestations of cardiac infectious-inflammatory disorders. Am J Emerg Med 2010;28:364-77.
57. Parker MM, Shelhamer JH, Bacharach SL, Green MV, Natanson C, Frederick TM, et al. Profound but reversible myocardial depression in patients with septic shock. Ann Intern Med 1984;100:483-90.
58. Huang SJ, Nalos M, McLean AS. Is early ventricular dysfunction or dilatation associated with lower mortality rate in adult severe sepsis and septic shock? A meta-Analysis. Crit Care 2013;17:R96.
59. Cunnion RE, Schaer GL, Parker MM, Natanson C, Parrillo JE. The coronary circulation in human septic shock. Circulation 1986;73:637-44.
60. Takasu O, Gaut JP, Watanabe E, To K, Fagley RE, Sato B, et al. Mechanisms of cardiac and renal dysfunction in patients dying of sepsis. Am J Respir Crit Care Med 2013;187:509-17.
61. Andresen M, Regueira T. Myocardial dysfunction in sepsis. Rev Med Chil 2010;138:888-96.
62. Muriova K, Malaska J, Otevrel F, Slezak M, Kratochvil M, Sevík P, et al. Myocardial dysfunction in sepsis-definition and pathogenetic mechanisms. Vnitr Lek 2010;56:220-5.
63. Duncan DJ, Hopkins PM, Harrison SM. Negative inotropic effects of tumour necrosis factor-Alpha and interleukin-1beta are ameliorated by alfentanil in rat ventricular myocytes. Br J Pharmacol 2007;150:720-6.
64. Rudiger A, Singer M. The heart in sepsis: From basic mechanisms to clinical management. Curr Vasc Pharmacol 2013;11:187-95.
65. Joulin O, Petillot P, Labalette M, Lancel S, Neviere R. Cytokine profile of human septic shock serum inducing cardiomyocyte contractile dysfunction. Physiol Res 2007;56:291-7.
66. Duncan DJ, Yang Z, Hopkins PM, Steele DS, Harrison SM. TNF-Alpha and IL-1beta increase Ca2+ leak from the sarcoplasmic reticulum and susceptibility to arrhythmia in rat ventricular myocytes. Cell Calcium 2010;47:378-86.
67. Maass DL, White J, Sanders B, Horton JW. Role of cytosolic vs. mitochondrial Ca2+ accumulation in burn injury-related myocardial inflammation and function. Am J Physiol Heart Circ Physiol 2005;288:H744-51.
68. Lupia E, Goffi A, Bosco O, Montrucchio G. Thrombopoietin as biomarker and mediator of cardiovascular damage in critical diseases. Mediators Inflamm 2012;2012:390892.
69. Aziz M, Jacob A, Yang WL, Matsuda A, Wang P. Current trends in inflammatory and immunomodulatory mediators in sepsis. J Leukoc Biol 2012;93:329-42.
70. Levine AB, Punihaole D, Levine TB. Characterization of the role of nitric oxide and its clinical applications. Cardiology 2012;122:55-68.
71. Sips PY, Irie T, Zou L, Shinozaki S, Sakai M, Shimizu N, et al. Reduction of cardiomyocyte S-nitrosylation by S-nitrosoglutathione reductase protects against sepsisinduced myocardial depression. Am J Physiol Heart Circ Physiol 2013;304:H1134-46.
72. Ichinose F, Buys ES, Neilan TG, Furutani EM, Morgan JG, Jassal DS, et al. Cardiomyocyte-specific overexpression of nitric oxide synthase 3 prevents myocardial dysfunction in murine models of septic shock. Circ Res 2007;100:130-9.
73. Lin NT, Yang FL, Lee RP, Peng TC, Chen HI. Inducible nitric oxide synthase mediates cytokine release: The time course in conscious and septic rats. Life Sci 2006;78:1038-43.
74. De Kock I, Van Daele C, Poelaert J. Sepsis and septic shock: Pathophysiological and cardiovascular background as basis for therapy. Acta Clin Belg 2010;65:323-9.
75. Zang Q, Maass DL, Tsai SJ, Horton JW. Cardiac mitochondrial damage and inflammation responses in sepsis. Surg Infect 2007;8:41-54.
76. Zang QS, Sadek H, Maass DL, Martinez B, Ma L, Kilgore JA, et al. Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model. Am J Physiol Heart Circ Physiol 2012;302:H1847-59.
77. Wu LL, Tang C, Liu MS. Altered phosphorylation and calcium sensitivity of cardiac myofibrillar proteins during sepsis. Am J Physiol Regul Integr Comp Physiol 2001;281:R408-16.
78. Yasuda S, Lew WY. Lipopolysaccharide depresses cardiac contractility and beta-Adrenergic contractile response by decreasing myofilament response to Ca2+ in cardiac myocytes. Circ Res 1997;81:1011-20.
79. Tavernier B, Li JM, El-Omar MM, Lanone S, Yang ZK, Trayer IP, et al. Cardiac contractile impairment associated with increased phosphorylation of troponin I in endotoxemic rats. FASEB J 2001;15:294-6.
80. Oldner A, Konrad D, Weitzberg E, Rudehill A, Rossi P, Wanecek M, et al. Effects of levosimendan, a novel inotropic calcium-sensitizing drug, in experimental septic shock. Crit Care Med 2001;29:2185-93.
81. Behrends M, Peters J. The calcium sensitizer levosimendan attenuates endotoxin-evoked myocardial dysfunction in isolated guinea pig hearts. Intensive Care Med 2003;29:1802-7.
82. Zhong J, Hwang TC, Adams HR, Rubin LJ. Reduced L-Type calcium current in ventricular myocytes from endotoxemic guinea pigs. Am J Physiol 1997;273:H2312-24.
83. Dong LW, Wu LL, Ji Y, Liu MS. Impairment of the ryanodinesensitive calcium release channels in the cardiac sarcoplasmic reticulum and its underlying mechanism during the hypodynamic phase of sepsis. Shock 2001;16:33-9.
84. Wu G, Yang SL, Hsu C, Yang RC, Hsu HK, Liu N, et al. Transcriptional regulation of cardiac sarcoplasmic reticulum calcium-ATPase gene during the progression of sepsis. Shock 2004;22:46-50.
85. Wu LL, Tang C, Dong LW, Liu MS. Altered phospholambancalcium ATPase interaction in cardiac sarcoplasmic reticulum during the progression of sepsis. Shock 2002;17:389-93.
86. Steendijk P. Sepsis and intracellular calcium homeostasis, a sparkling story. Crit Care Med 2005;33:688-90.
87. Takayama TK, Miller C, Szabo G. Elevated tumor necrosis factor alpha production concomitant to elevated prostaglandin E2 production by trauma patients monocytes. Arch Surg 1990;125:29-35.
88. Kalogeropoulos AP, Georgiopoulou VV, Butler J. From risk factors to structural heart disease: The role of inflammation. Heart Fail Clin 2012;8:113-23.
89. Cheng YJ, Lang D, Caruthers SD, Efimov IR, Chen J, Wickline SA, et al. Focal but reversible diastolic sheet dysfunction reflects regional calcium mishandling in dystrophic mdx mouse hearts. Am J Physiol Heart Circ Physiol 2012;303:H559-68.
90. Chao W. Toll-like receptor signaling:a critical modulator of cell survival and ischemic injury in the heart. Am J Physiol Heart Circ Physiol 2009;296:H1-12.
91. Feng Y, Chao W. Toll-like receptors and myocardial inflammation. Int J Inflam 2011;2011:170352.
92. Glembotski CC, Irons CE, Krown KA, Murray SF, Sprenkle AB, Sei CA, et al. Myocardial alpha-Thrombin receptor activation induces hypertrophy and increases atrial natriuretic factor gene expression. J Biol Chem 1993;268:20646-52.
93. Palmer JN, Hartogensis WE, Patten M, Fortuin FD, Long CS Interleukin-1 beta induces cardiac myocyte growth but inhibits cardiac fibroblast proliferation in culture. J Clin Invest 1995;95:2555-64.
94. Kurdi M, Randon J, Cerutti C, Bricca G. Increased expression of IL-6 and LIF in the hypertrophied left ventricle of TGR (mRen2) 27 and SHR rats. Mol Cell Biochem 2005;269:95-101.
95. Wang M, Markel TA, Meldrum DR. Interleukin 18 in the heart. Shock 2008;30:3-10.
96. Post F, Weilemann LS, Messow CM, Sinning C, Munzel T. B-Type natriuretic peptide as a marker for sepsis-induced myocardial depression in intensive care patients. Crit Care Med 2008;36:3030-7.
97. Rudiger A, Dyson A, Felsmann K, Carre JE, Taylor V, Hughes S, et al. Early functional and transcriptomic changes in the myocardium predict outcome in a long-Term rat model of sepsis. Clin Sci 2013;124:391-401.
98. Rodino-Klapac LR, Mendell JR, Sahenk Z. Update on the treatment of Duchenne muscular dystrophy. Curr Neurol Neurosci Rep 2013;13:332.
99. Mosqueira M, Zeiger U, Forderer M, Brinkmeier H, Fink RH. Cardiac and respiratory dysfunction in Duchenne muscular dystrophy and the role of second messengers. Med Res Rev 2013;33:1174-213.
100. Tabas I, Glass CK. Anti-inflammatory therapy in chronic disease: Challenges and opportunities. Science 2013;339:166-72.
101. Marik PE, Flemmer M. The immune response to surgery and trauma: Implications for treatment. J Trauma Acute Care Surg 2012;73:801-8.
102. Rudiger A. Beta-block the septic heart. Crit Care Med 2010;38(10 Suppl):S608-612.
103. Berk JL, Hagen JF, Beyer WH, Gerber MJ, Dochat GR. The treatment of endotoxin shock by beta adrenergic blockade. Ann Surg 1969;169:74-81.
104. Suzuki T, Morisaki H, Serita R, Yamamoto M, Kotake Y, Ishizaka A, et al. Infusion of the beta-Adrenergic blocker esmolol attenuates myocardial dysfunction in septic rats. Crit Care Med 2005;33:2294-301.
105. Herndon DN, Hart DW, Wolf SE, Chinkes DL, Wolfe RR (2001) Reversal of catabolism by beta-blockade after severe burns. N Engl J Med 345:1223-1229.
106. Arbabi S, Ahrns KS, Wahl WL, Hemmila MR, Wang SC, Brandt MM, et al. Beta-blocker use is associated with improved outcomes in adult burn patients. J Trauma 2004;56:265-9; discussion 269-71.
107. Arab HH, El-Sawalhi MM. Carvedilol alleviates adjuvantinduced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators. Toxicol Appl Pharmacol 2013;268:241-8.
108. O Keefe JH, Lurk JT, Kahatapitiya RC, Haskin JA. The reninangiotensin-aldosterone system as a target in coronary disease. Curr Atheroscler Rep 2003;5:124-30.
109. Tsikouris JP, Cox CD. Pharmacologic blockade of the reninangiotensin system: Vascular benefits beyond commonly understood pharmacologic actions. Pharmacotherapy 2003;23:1141-52.
110. White M, Racine N, Ducharme A, de Champlain J. Therapeutic potential of angiotensin II receptor antagonists. Expert Opin Investig Drugs 2001;10:1687-701.
111. Bangash MN, Kong ML, Pearse RM. Use of inotropes and vasopressor agents in critically ill patients. Br J Pharmacol 2012;165:2015-33.
112. Rognoni A, Lupi A, Lazzero M, Bongo AS, Rognoni G. Levosimendan: From basic science to clinical trials. Recent Pat Cardiovasc Drug Discov 2011;6:9-15.
113. Pathak A, Lebrin M, Vaccaro A, Senard JM, Despas F. Pharmacology of levosimendan: Inotropic, vasodilatory and cardioprotective effects. J Clin Pharm Ther 2013;38:341-9.
114. Toller WG, Stranz C. Levosimendan, a new inotropic and vasodilator agent. Anesthesiology 2006;104:556-69.
115. Karakus E, Halici Z, Albayrak A, Bayir Y, Aydin A, Unal D, et al. Beneficial pharmacological effects of levosimendan on antioxidant status of acute inflammation induced in paw of rat: Involvement in inflammatory mediators. Basic Clin Pharmacol Toxicol 2013;112:156-63.
116. Doorduin J, Sinderby CA, Beck J, Stegeman DF, van Hees HW, van der Hoeven JG, et al. The calcium sensitizer levosimendan improves human diaphragm function. Am J Respir Crit Care Med 2012;185:90-5.
117. Williams FN, Herndon DN, Suman OE, Lee JO, Norbury WB, Branski LK, et al. Changes in cardiac physiology after severe burn injury. J Burn Care Res 2011;32:269-74.
118. Leibovici L, Gafter-Gvili A, Paul M, Almanasreh N, Tacconelli E, Andreassen S, et al. Relative tachycardia in patients with sepsis: An independent risk factor for mortality. QJM 2007;100:629-34.
119. Ivanovic BA, Tadic M, Dincic D. Heart rate-predictor of cardiovascular risk. Vojnosanit Pregl 2012;69:799-802.
120. Speranza L, Franceschelli S, Riccioni G. The biological effects of ivabradine in cardiovascular disease. Molecules 2012;17:4924-35.
121. Finsterer J, Stollberger C, Berger E. Beneficial effect of ivabradine in dilated cardiomyopathy from Becker muscular dystrophy. Herz 2012;37:702-5.