Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper

International Journal of Cardiology

Volumn 222, Issue , 2016, Pages 303-312

  Farmakis, Dimitrios ^a   Alvarez, Julian ^b   Gal, Tuvia Ben ^c   Brito, Dulce ^d   Fedele, Francesco ^e   Fonseca, Candida ^f   Gordon, Anthony C ^g   Gotsman, Israel ^h   Grossini, Elena ⁱ   Guarracino, Fabio ^j   Harjola, Veli Pekka ^k   Hellman, Yaron ^l   Heunks, Leo ^m   Ivancan, Visnja ⁿ   Karavidas, Apostolos ^o   Kivikko, Matti ^p   Lomivorotov, Vladimir ^q   Longrois, Dan ^r   Masip, Josep ^s   Metra, Marco ^t   Morelli, Andrea ^e   Nikolaou, Maria ^u   Papp, Zoltán ^v   Parkhomenko, Alexander ^w   Poelzl, Gerhard ^x   Pollesello, Piero ^p   Ravn, Hanne Berg ^y   Rex, Steffen ^z   Riha, Hynek ^aa   Ricksten, Sven Erik ^ab   Schwinger, Robert H G ^ac   Vrtovec, Bojan ^ad   Yilmaz, M Birhan ^ae   Zielinska, Marzenna ^af   Parissis, John ^a   more..

^a UNIVERSITY OF ATHENS   (Greece)

^b UNIVERSITY OF SANTIAGO DE COMPOSTELA   (Spain)

^c RABIN MEDICAL CENTER   (Israel)

^d HOSPITAL DE SANTA MARIA   (Portugal)

^e SAPIENZA UNIVERSITY OF ROME   (Italy)

^f NOVA MEDICAL SCHOOL   (Portugal)

^g IMPERIAL COLLEGE LONDON   (United Kingdom)

^h HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

ⁱ UNIVERSITY OF EASTERN PIEDMONT   (Italy)

^j UNIVERSITY HOSPITAL OF PISA   (Italy)

^k UNIVERSITY OF HELSINKI   (Finland)

^l CARMEL MEDICAL CENTER   (Israel)

^m RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

ⁿ KBC Zagreb   (Croatia)

^o G GENNIMATAS GENERAL HOSPITAL   (Greece)

^p ORION CORPORATION   (Finland)

^q MESHALKIN NATIONAL MEDICAL RESEARCH CENTER   (Russian Federation)

^r BICHAT HOSPITAL   (France)

^s Hospital de Sant Joan Despi Moises Broggi   (Spain)

^t Civil Hospital   (Italy)

^u AMALIA FLEMING GENERAL HOSPITAL   (Greece)

^v UNIVERSITY OF DEBRECEN   (Hungary)

^w Ukranian Strazhesko Institute of Cardiology   (Ukraine)

^x INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^y University of Copenhagen   (Denmark)

^z UNIVERSITY OF LEUVEN   (Belgium)

^aa INSTITUTE FOR CLINICAL AND EXPERIMENTAL MEDICINE   (Czech Republic)

^ab SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

^ac Klinikum Weiden   (Germany)

^ad UNIVERSITY MEDICAL CENTRE LJUBLJANA   (Slovenia)

^ae CUMHURIYET UNIVERSITY   (Turkey)

^af MEDICAL UNIVERSITY OF LODZ   (Poland)

more..

Author keywords

Cardiogenic shock; Cardioprotection; Heart failure; Inotropes; Levosimendan; Organ protection

Indexed keywords

LEVOSIMENDAN; ANTIARRHYTHMIC AGENT; CARDIOTONIC AGENT; HYDRAZONE DERIVATIVE; PYRIDAZINE DERIVATIVE; SIMENDAN;

ACUTE HEART FAILURE; ADVANCED HEART FAILURE; ANTIINFLAMMATORY ACTIVITY; BREATHING MUSCLE; CARDIOVASCULAR FUNCTION; CENTRAL NERVOUS SYSTEM; CORONARY ARTERY BLOOD FLOW; DIASTOLE; DRUG EFFECT; ENDOTHELIAL FUNCTION; HEART AFTERLOAD; HEART FAILURE; HEART MUSCLE CONTRACTILITY; HEART MUSCLE RELAXATION; HUMAN; INOTROPISM; INTESTINE; KIDNEY; LIVER; LUNG; NONHUMAN; PERIOPERATIVE PERIOD; PRIORITY JOURNAL; PROPHYLAXIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REPERFUSION INJURY; REVIEW; SEPSIS; SEPTIC SHOCK; SPLANCHNIC BLOOD FLOW; SUBARACHNOID HEMORRHAGE; VENTILATOR WEANING; VENTRICULO ARTERIAL COUPLING; ACUTE DISEASE; CLINICAL TRIAL (TOPIC); DRUG EFFECTS; EXPERT WITNESS; HEART; MUSCLE CONTRACTION; PATHOPHYSIOLOGY; PHYSIOLOGY; PROCEDURES; STANDARDS; TREATMENT OUTCOME;

ACUTE DISEASE; ANTI-ARRHYTHMIA AGENTS; CARDIOTONIC AGENTS; CLINICAL TRIALS AS TOPIC; EXPERT TESTIMONY; HEART; HEART FAILURE; HUMANS; HYDRAZONES; MUSCLE CONTRACTION; PYRIDAZINES; TREATMENT OUTCOME;

EID: 84980320215     PISSN: 01675273     EISSN: 18741754     Source Type: Journal    
DOI: 10.1016/j.ijcard.2016.07.202     Document Type: Review

References (133)

1. [1] Pollesello, P., Papp, Z., Papp, J.G., Calcium sensitizers: what have we learned over the last 25 years?. Int. J. Cardiol. 203 (2016), 543–548.
2. [2] Parissis, J.T., Farmakis, D., Nieminen, M., Classical inotropes and new cardiac enhancers. Heart Fail. Rev. 12 (2007), 149–156.
3. [3] Haikala, H., Kaivola, J., Nissinen, E., Wall, P., Levijoki, J., Lindén, I.B., Cardiac troponin C as a target protein for a novel calcium sensitizing drug, levosimendan. J. Mol. Cell. Cardiol. 27 (1995), 1859–1866.
4. [4] Katz, A.M., Regulation of myocardial contractility 1958–1983: an odyssey. J. Am. Coll. Cardiol. 1 (1983), 42–51.
5. [5] Hasenfuss, G., Pieske, B., Castell, M., Kretschmann, B., Maier, L.S., Just, H., Influence of the novel inotropic agent levosimendan on isometric tension and calcium cycling in failing human myocardium. Circulation 98 (1998), 2141–2147.
6. [6] Pagel, P.S., McGough, M.F., Hettrick, D.A., Lowe, D., Tessmer, J.P., Jamali, I.N., Warltier, D.C., Levosimendan enhances left ventricular systolic and diastolic function in conscious dogs with pacing-induced cardiomyopathy. J. Cardiovasc. Pharmacol. 29 (1997), 563–573.
7. [7] Tachibana, H., Cheng, H.J., Ukai, T., Igawa, A., Zhang, Z.S., Little, W.C., Cheng, C.P., Levosimendan improves LV systolic and diastolic performance at rest and during exercise after heart failure. Am. J. Physiol. Heart Circ. Physiol. 288 (2005), H914–H922.
8. [8] Brixius, K., Reicke, S., Schwinger, R.H., Beneficial effects of the Ca(2 +) sensitizer levosimendan in human myocardium. Am. J. Physiol. Heart Circ. Physiol. 282 (2002), H131–H137.
9. [9] Kawabata, H., Ryomoto, T., Ishikawa, K., Role of cardiac ATP-sensitive K + channels induced by angiotensin II type 1 receptor antagonist on metabolism, contraction and relaxation in ischemia-reperfused rabbit heart. Jpn. Circ. J. 65 (2001), 451–456.
10. [10] Givertz, M.M., Andreou, C., Conrad, C.H., Colucci, W.S., Direct myocardial effects of levosimendan in humans with left ventricular dysfunction: alteration of force-frequency and relaxation-frequency relationships. Circulation 115 (2007), 1218–1224.
11. [11] Parissis, J.T., Panou, F., Farmakis, D., Adamopoulos, S., Filippatos, G., Paraskevaidis, I., Venetsanou, K., Lekakis, J., Kremastinos, D.T., Effects of levosimendan on markers of left ventricular diastolic function and neurohormonal activation in patients with advanced heart failure. Am. J. Cardiol. 96 (2005), 423–426.
12. [12] Malik, V., Subramanian, A., Hote, M., Kiran, U., Effect of levosimendan on diastolic function in patients undergoing coronary artery bypass grafting: a comparative study. J. Cardiovasc. Pharmacol. 66 (2015), 141–147.
13. [13] Jörgensen, K., Bech-Hanssen, O., Houltz, E., Ricksten, S.E., Effects of levosimendan on left ventricular relaxation and early filling at maintained preload and afterload conditions after aortic valve replacement for aortic stenosis. Circulation 117 (2008), 1075–1081.
14. [14] Sonntag, S., Sundberg, S., Lehtonen, L.A., Kleber, F.X., The calcium sensitizer levosimendan improves the function of stunned myocardium after percutaneous transluminal coronary angioplasty in acute myocardial ischemia. J. Am. Coll. Cardiol. 43 (2004), 2177–2182.
15. [15] Louhelainen, M., Merasto, S., Finckenberg, P., Vahtola, E., Kaheinen, P., Leskinen, H., Levijoki, J., Pollesello, P., Haikala, H., Mervaala, E.M., Effects of calcium sensitizer OR-1986 on a cardiovascular mortality and myocardial remodelling in hypertensive Dahl/Rapp rats. J. Physiol. Pharmacol. 60 (2009), 41–47.
16. [16] Louhelainen, M., Vahtola, E., Kaheinen, P., Leskinen, H., Merasto, S., Kytö, V., Finckenberg, P., Colucci, W.S., Levijoki, J., Pollesello, P., Haikala, H., Mervaala, E.M., Effects of levosimendan on cardiac remodeling and cardiomyocyte apoptosis in hypertensive Dahl/Rapp rats. Br. J. Pharmacol. 150 (2007), 851–861.
17. [17] Vahtola, E., Storvik, M., Louhelainen, M., Merasto, S., Lakkisto, P., Lakkisto, J., Tikkanen, I., Kaheinen, P., Levijoki, J., Mervaala, E., Effects of levosimendan on cardiac gene expression profile and post-infarct cardiac remodelling in diabetic Goto-Kakizaki rats. Basic Clin. Pharmacol. Toxicol. 109 (2011), 387–397.
18. [18] Louhelainen, M., Vahtola, E., Forsten, H., Merasto, S., Kytö, V., Finckenberg, P., Leskinen, H., Kaheinen, P., Tikkanen, I., Levijoki, J., Mervaala, E., Oral levosimendan prevents postinfarct heart failure and cardiac remodeling in diabetic Goto-Kakizaki rats. J. Hypertens. 27 (2009), 2094–2107.
19. [19] Louhelainen, M., Merasto, S., Finckenberg, P., Vahtola, E., Kaheinen, P., Levijoki, J., Mervaala, E., Effects of the calcium sensitizer OR-1896, a metabolite of levosimendan, on post-infarct heart failure and cardiac remodelling in diabetic Goto-Kakizaki rats. Br. J. Pharmacol. 160 (2010), 142–152.
20. [20] Okada, M., Suzuki, A., Yamawaki, H., Hara, Y., Levosimendan inhibits interleukin-1β-induced cell migration and MMP-9 secretion in rat cardiac fibroblasts. Eur. J. Pharmacol. 718 (2013), 332–339.
21. [21] Tziakas, D.N., Chalikias, G.K., Hatzinikolaou, H.I., Stakos, D.A., Papanas, N., Tentes, I.K., Kortsaris, A.X., Maltezos, E., Hatseras, D.I., Kaski, J.C., Levosimendan use reduces matrix metalloproteinase-2 in patients with decompensated heart failure. Cardiovasc. Drugs Ther. 19 (2005), 399–402.
22. [22] Kasikcioglu, H.A., Unal, S., Tartan, Z., Uyarel, H., Okmen, E., Kasikcioglu, E., Cam, N., Effects of levosimendan on left ventricular functional remodelling and exercise intolerance: a tissue Doppler study. J. Int. Med. Res. 33 (2005), 397–405.
23. [23] Grossini, E., Molinari, C., Caimmi, P.P., Uberti, F., Vacca, G., Levosimendan induces NO production through p38 MAPK, ERK and Akt in porcine coronary endothelial cells: role for mitochondrial K(ATP) channel. Br. J. Pharmacol. 156 (2009), 250–261.
24. [24] Parissis, J.T., Karavidas, A., Bistola, V., Arapi, S., Paraskevaidis, I.A., Farmakis, D., Korres, D., Filippatos, G., Matsakas, E., Kremastinos, D.T., Effects of levosimendan on flow-mediated vasodilation and soluble adhesion molecules in patients with advanced chronic heart failure. Atherosclerosis 197 (2008), 278–282.
25. [25] Pagel, P.S., Hettrick, D.A., Warltier, D.C., Comparison of the effects of levosimendan, pimobendan, and milrinone on canine left ventricular-arterial coupling and mechanical efficiency. Basic Res. Cardiol. 91 (1996), 296–307.
26. [26] Missant, C., Rex, S., Segers, P., Wouters, P.F., Levosimendan improves right ventriculovascular coupling in a porcine model of right ventricular dysfunction. Crit. Care Med. 35 (2007), 707–715.
27. [27] Guarracino, F., Cariello, C., Danella, A., Doroni, L., Lapolla, F., Stefani, M., Baldassarri, R., Vullo, C., Effect of levosimendan on ventriculo-arterial coupling in patients with ischemic cardiomyopathy. Acta Anaesthesiol. Scand. 51 (2007), 1217–1224.
28. [28] Pollesello, P., Papp, Z., The cardioprotective effects of levosimendan: preclinical and clinical evidence. J. Cardiovasc. Pharmacol. 50 (2007), 257–263.
29. [29] du Toit, E.F., Genis, A., Opie, L.H., Pollesello, P., Lochner, A., A role for the RISK pathway and K(ATP) channels in pre- and post-conditioning induced by levosimendan in the isolated guinea pig heart. Br. J. Pharmacol. 154 (2008), 41–50.
30. [30] Das, B., Sarkar, C., Pharmacological preconditioning by levosimendan is mediated by inducible nitric oxide synthase and mitochondrial KATP channel activation in the in vivo anesthetized rabbit heart model. Vasc. Pharmacol. 47 (2007), 248–256.
31. [31] Leprán, I., Pollesello, P., Vajda, S., Varró, A., Papp, J.G., Preconditioning effects of levosimendan in a rabbit cardiac ischemia-reperfusion model. J. Cardiovasc. Pharmacol. 48 (2006), 148–152.
32. [32] Hönisch, A., Theuring, N., Ebner, B., Wagner, C., Strasser, R.H., Weinbrenner, C., Postconditioning with levosimendan reduces the infarct size involving the PI3K pathway and KATP-channel activation but is independent of PDE-III inhibition. Basic Res. Cardiol. 105:2 (2010), 155–167.
33. [33] Metzsch, C., Linnér, R., Steen, S., Liao, Q., Algotsson, L., Levosimendan cardioprotection in acutely beta-1 adrenergic receptor blocked open chest pigs. Acta Anaesthesiol. Scand. 54 (2010), 103–110.
34. [34] Tritapepe, L., De Santis, V., Vitale, D., Santulli, M., Morelli, A., Nofroni, I., Puddu, P.E., Singer, M., Pietropaoli, P., Preconditioning effects of levosimendan in coronary artery bypass grafting—a pilot study. Br. J. Anaesth. 96 (2006), 694–700.
35. [35] De Luca, L., Sardella, G., Proietti, P., Battagliese, A., Benedetti, G., Di Roma, A., Fedele, F., Effects of levosimendan on left ventricular diastolic function after primary angioplasty for acute anterior myocardial infarction: a Doppler echocardiographic study. J. Am. Soc. Echocardiogr. 19 (2006), 172–177.
36. [36] Montes, F.R., Echeverri, D., Buitrago, L., Ramírez, I., Giraldo, J.C., Maldonado, J.D., Umaña, J.P., The vasodilatory effects of levosimendan on the human internal mammary artery. Anesth. Analg. 103 (2006), 1094–1098.
37. [37] Ambrus, N., Szolnoky, J., Pollesello, P., Kun, A., Varró, A., Papp, J.G., Pataricza, J., Prolonged antispasmodic effect in isolated radial artery graft and pronounced platelet inhibition induced by the inodilator drug, levosimendan. Basic Clin. Pharmacol. Toxicol. 110 (2012), 269–274.
38. [38] Krychtiuk, K.A., Watzke, L., Kaun, C., Buchberger, E., Hofer-Warbinek, R., Demyanets, S., Pisoni, J., Kastl, S.P., Rauscher, S., Gröger, M., Aliabadi, A., Zuckermann, A., Maurer, G., de Martin, R., Huber, K., Wojta, J., Speidl, W.S., Levosimendan exerts anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro. Thromb. Haemost. 113 (2015), 350–362.
39. [39] Hasslacher, J., Bijuklic, K., Bertocchi, C., Kountchev, J., Bellmann, R., Dunzendorfer, S., Joannidis, M., Levosimendan inhibits release of reactive oxygen species in polymorphonuclear leukocytes in vitro and in patients with acute heart failure and septic shock: a prospective observational study. Crit. Care, 15, 2011, R166.
40. [40] Parissis, J.T., Adamopoulos, S., Antoniades, C., Kostakis, G., Rigas, A., Kyrzopoulos, S., Iliodromitis, E., Kremastinos, D., Effects of levosimendan on circulating pro-inflammatory cytokines and soluble apoptosis mediators in patients with decompensated advanced heart failure. Am. J. Cardiol. 93 (2004), 1309–1312.
41. [41] Parissis, J.T., Adamopoulos, S., Farmakis, D., Filippatos, G., Paraskevaidis, I., Panou, F., Iliodromitis, E., Kremastinos, D.T., Effects of serial levosimendan infusions on left ventricular performance and plasma biomarkers of myocardial injury and neurohormonal and immune activation in patients with advanced heart failure. Heart 92 (2006), 1768–1772.
42. [42] Parissis, J.T., Andreadou, I., Markantonis, S.L., Bistola, V., Louka, A., Pyriochou, A., Paraskevaidis, I., Filippatos, G., Iliodromitis, E.K., Kremastinos, D.T., Effects of levosimendan on circulating markers of oxidative and nitrosative stress in patients with advanced heart failure. Atherosclerosis 195 (2007), e210–e215.
43. [43] Trikas, A., Antoniades, C., Latsios, G., Vasiliadou, K., Karamitros, I., Tousoulis, D., Tentolouris, C., Stefanadis, C., Long-term effects of levosimendan infusion on inflammatory processes and sFas in patients with severe heart failure. Eur. J. Heart Fail. 8 (2006), 804–809.
44. [44] Grossini, E., Molinari, C., Pollesello, P., Bellomo, G., Valente, G., Mary, D., Vacca, G., Caimmi, P., Levosimendan protection against kidney ischemia/reperfusion injuries in anesthetized pigs. J. Pharmacol. Exp. Ther. 342 (2012), 376–388.
45. [45] Yakut, N., Yasa, H., Bahriye Lafci, B., Ortac, R., Tulukoglu, E., Aksun, M., Ozbek, C., Gurbuz, A., The influence of levosimendan and iloprost on renal ischemia-reperfusion: an experimental study. Interact. Cardiovasc. Thorac. Surg. 7 (2008), 235–239.
46. [46] Gecit, I., Kavak, S., Yüksel, M.B., Basel, H., Bektas, H., Gümrükçüoglu, H.A., Meral, I., Demir, H., Effect of short-term treatment with levosimendan on oxidative stress in renal tissues of rats. Toxicol. Ind. Health 30 (2014), 47–51.
47. [47] Zager, R.A., Johnson, A.C., Lund, S., Hanson, S.Y., Abrass, C.K., Levosimendan protects against experimental endotoxemic acute renal failure. Am. J. Physiol. Ren. Physiol. 290 (2006), F1453–F1462.
48. [48] Yilmaz, M.B., Grossini, E., Silva Cardoso, J.C., Édes, I., Fedele, F., Pollesello, P., Kivikko, M., Harjola, V.P., Hasslacher, J., Mebazaa, A., Morelli, A., le Noble, J., Oldner, A., Oulego Erroz, I., Parissis, J.T., Parkhomenko, A., Poelzl, G., Rehberg, S., Ricksten, S.E., Rodríguez Fernández, L.M., Salmenperä, M., Singer, M., Treskatsch, S., Vrtovec, B., Wikström, G., Renal effects of levosimendan: a consensus report. Cardiovasc. Drugs Ther. 27 (2013), 581–590.
49. [49] Bragadottir, G., Redfors, B., Ricksten, S.E., Effects of levosimendan on glomerular filtration rate, renal blood flow, and renal oxygenation after cardiac surgery with cardiopulmonary bypass: a randomized placebo-controlled study. Crit. Care Med. 41 (2013), 2328–2335.
50. [50] Baysal, A., Yanartas, M., Dogukan, M., Gundogus, N., Kocak, T., Koksal, C., Levosimendan improves renal outcome in cardiac surgery: a randomized trial. J. Cardiothorac. Vasc. Anesth. 28 (2014), 586–594.
51. [51] Fedele, F., Bruno, N., Brasolin, B., Caira, C., D'Ambrosi, A., Mancone, M., Levosimendan improves renal function in acute decompensated heart failure: possible underlying mechanisms. Eur. J. Heart Fail. 16 (2014), 281–288.
52. [52] Knezevic, I., Poglajen, G., Hrovat, E., Oman, A., Pintar, T., Wu, J.C., Vrtovec, B., Haddad, F., The effects of levosimendan on renal function early after heart transplantation: results from a pilot randomized trial. Clin. Transpl. 28 (2014), 1105–1111.
53. [53] Niu, Z.Z., Wu, S.M., Sun, W.Y., Hou, W.M., Chi, Y.F., Perioperative levosimendan therapy is associated with a lower incidence of acute kidney injury after cardiac surgery: a meta-analysis. J. Cardiovasc. Pharmacol. 63 (2014), 107–112.
54. [54] Zhou, C., Gong, J., Chen, D., Wang, W., Liu, M., Liu, B., Levosimendan for prevention of acute kidney injury after cardiac surgery: a meta-analysis of randomized controlled trials. Am. J. Kidney Dis. 67 (2016), 408–416.
55. [55] Bove, T., Matteazzi, A., Belletti, A., Paternoster, G., Saleh, O., Taddeo, D., Dossi, R., Greco, T., Bradic, N., Husedzinovic, I., Nigro Neto, C., Lomivorotov V6, Calabrò MG. Beneficial impact of levosimendan in critically ill patients with or at risk for acute renal failure: a meta-analysis of randomized clinical trials. Heart Lung Vessel 7 (2015), 35–46.
56. [56] Yilmaz, M.B., Yalta, K., Yontar, C., Karadas, F., Erdem, A., Turgut, O.O., Yilmaz, A., Tandogan, I., Levosimendan improves renal function in patients with acute decompensated heart failure: comparison with dobutamine. Cardiovasc. Drugs Ther. 21 (2007), 431–435.
57. [57] Hou, Z.Q., Sun, Z.X., Su, C.Y., Tan, H., Zhong, X., Hu, B., Zhou, Y., Shang, D.Y., Effect of levosimendan on estimated glomerular filtration rate in hospitalized patients with decompensated heart failure and renal dysfunction. Cardiovasc. Ther. 31 (2013), 108–114.
58. [58] Rafouli-Stergiou, P., Parissis, J.T., Farmakis, D., Bistola, V., Frogoudaki, A., Vasiliadis, K., Ikonomidis, I., Paraskevaidis, I., Kremastinos, D., Filippatos, G., Lekakis, J., Effects of levosimendan on markers of kidney function in patients with acutely decompensated heart failure and renal impairment. J. Cardiovasc. Med. (Hagerstown), 31, 2015 Jan (Epub ahead of print).
59. [59] Zemljic, G., Bunc, M., Yazdanbakhsh, A.P., Vrtovec, B., Levosimendan improves renal function in patients with advanced chronic heart failure awaiting cardiac transplantation. J. Card. Fail. 13 (2007), 417–421.
60. [60] Grossini, E., Pollesello, P., Bellofatto, K., Sigaudo, L., Farruggio, S., Origlia, V., Mombello, C., Mary, D.A., Valente, G., Vacca, G., Protective effects elicited by levosimendan against liver ischemia/reperfusion injury in anesthetized rats. Liver Transpl. 20 (2014), 361–375.
61. [61] Grossini, E., Bellofatto, K., Farruggio, S., Sigaudo, L., Marotta, P., Raina, G., De Giuli, V., Mary, D., Pollesello, P., Minisini, R., Pirisi, M., Vacca, G., Levosimendan inhibits peroxidation in hepatocytes by modulating apoptosis/autophagy interplay. PLoS One, 10, 2015, e0124742.
62. [62] Onody, P., Stangl, R., Fulop, A., Rosero, O., Garbaisz, D., Turoczi, Z., Lotz, G., Rakonczay, Z. Jr., Balla, Z., Hegedus, V., Harsanyi, L., Szijarto, A., Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury?. PLoS One, 8, 2013, e73758.
63. [63] Ibrahim, M.A., Abdel-Gaber, S.A., Amin, E.F., Ibrahim, S.A., Mohammed, R.K., Abdelrahman, A.M., Molecular mechanisms contributing to the protective effect of levosimendan in liver ischemia-reperfusion injury. Eur. J. Pharmacol. 741 (2014), 64–73.
64. [64] Pagel, P.S., Hettrick, D.A., Warltier, D.C., Influence of levosimendan, pimobendan, and milrinone on the regional distribution of cardiac output in anaesthetized dogs. Br. J. Pharmacol. 119 (1996), 609–615.
65. [65] García-Septien, J., Lorente, J.A., Delgado, M.A., de Paula, M., Nin, N., Moscoso, A., Sánchez-Ferrer, A., Perez-Vizcaino, F., Esteban, A., Levosimendan increases portal blood flow and attenuates intestinal intramucosal acidosis in experimental septic shock. Shock 34 (2010), 275–280.
66. [66] Alvarez, J., Baluja, A., Selas, S., Otero, P., Rial, M., Veiras, S., Caruezo, V., Taboada, M., Rodriguez, I., Castroagudin, J., Tome, S., Rodriguez, A., Rodriguez, J., A comparison of dobutamine and levosimendan on hepatic blood flow in patients with a low cardiac output state after cardiac surgery: a randomised controlled study. Anaesth. Intensive Care 41 (2013), 719–727.
67. [67] Memiş, D., Inal, M.T., Sut, N., The effects of levosimendan vs dobutamine added to dopamine on liver functions assessed with noninvasive liver function monitoring in patients with septic shock. J. Crit. Care, 27, 2012 (318.e1–6).
68. [68] Schwarte, L.A., Picker, O., Bornstein, S.R., Fournell, A., Scheeren, T.W., Levosimendan is superior to milrinone and dobutamine in selectively increasing microvascular gastric mucosal oxygenation in dogs. Crit. Care Med. 33 (2005), 135–142 (discussion 246–7).
69. [69] Dubin, A., Murias, G., Sottile, J.P., Pozo, M.O., Barán, M., Edul, V.S., Canales, H.S., Etcheverry, G., Maskin, B., Estenssoro, E., Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study. Intensive Care Med. 33 (2007), 485–494.
70. [70] Cunha-Goncalves, D., Perez-de-Sa, V., Grins, E., Dahm, P.L., Thörne, J., Blomquist, S., Inotropic support during experimental endotoxemic shock: part I. The effects of levosimendan on splanchnic perfusion. Anesth. Analg. 109 (2009), 1568–1575.
71. [71] Leppikangas, H., Tenhunen, J.J., Lindgren, L., Salenius, J.P., Ruokonen, E., Effects of levosimendan on indocyanine green plasma disappearance rate and the gastric mucosal-arterial pCO2 gradient in abdominal aortic aneurysm surgery. Acta Anaesthesiol. Scand. 52 (2008), 785–792.
72. [72] Zhang, C., Guo, Z., Liu, H., Shi, Y., Ge, S., Influence of levosimendan postconditioning on apoptosis of rat lung cells in a model of ischemia-reperfusion injury. PLoS One, 10, 2015, e0114963.
73. [73] Wang, X., Ma, S., Liu, Y., Xu, W., Li, Z., Effects and mechanism analysis of combined infusion by levosimendan and vasopressin on acute lung injury in rats septic shock. Cell Biochem. Biophys. 70 (2014), 1639–1645.
74. [74] Erbüyün, K., Vatansever, S., Tok, D., Ok, G., Türköz, E., Aydede, H., Erhan, Y., Tekin, I., Effects of levosimendan and dobutamine on experimental acute lung injury in rats. Acta Histochem. 111 (2009), 404–414.
75. [75] Alkan, M., Çelik, A., Bilge, M., Kiraz, H.A., Kip, G., Özer, A., Şıvgın, V., Erdem, Ö., Arslan, M., Kavutçu, M., The effect of levosimendan on lung damage after myocardial ischemia reperfusion in rats in which experimental diabetes was induced. J. Surg. Res. 193 (2015), 920–925.
76. [76] Yasa, H., Yakut, N., Emrecan, B., Ergunes, K., Ortac, R., Karahan, N., Ozbek, C., Gurbuz, A., Protective effects of levosimendan and iloprost on lung injury induced by limb ischemia-reperfusion: a rabbit model. J. Surg. Res. 147 (2008), 138–142.
77. [77] Boost, K.A., Hoegl, S., Dolfen, A., Czerwonka, H., Scheiermann, P., Zwissler, B., Hofstetter, C., Inhaled levosimendan reduces mortality and release of proinflammatory mediators in a rat model of experimental ventilator-induced lung injury. Crit. Care Med. 36 (2008), 1873–1879.
78. [78] Rieg, A.D., Rossaint, R., Verjans, E., Maihöfer, N.A., Uhlig, S., Martin, C., Levosimendan relaxes pulmonary arteries and veins in precision-cut lung slices — the role of KATP-channels, cAMP and cGMP. PLoS One, 8, 2013, e66195.
79. [79] Morelli, A., Teboul, J.L., Maggiore, S.M., Vieillard-Baron, A., Rocco, M., Conti, G., De Gaetano, A., Picchini, U., Orecchioni, A., Carbone, I., Tritapepe, L., Pietropaoli, P., Westphal, M., Effects of levosimendan on right ventricular afterload in patients with acute respiratory distress syndrome: a pilot study. Crit. Care Med. 34 (2006), 2287–2293.
80. [80] Ottenheijm, C.A., Heunks, L.M., Sieck, G.C., Zhan, W.Z., Jansen, S.M., Degens, H., de Boo, T., Dekhuijzen, P.N., Diaphragm dysfunction in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 172 (2005), 200–205.
81. [81] van Hees, H.W., Dekhuijzen, P.N., Heunks, L.M., Levosimendan enhances force generation of diaphragm muscle from patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 179 (2009), 41–47.
82. [82] Schellekens, W.J., van Hees, H.W., Linkels, M., Dekhuijzen, P.N., Scheffer, G.J., van der Hoeven, J.G., Heunks, L.M., Levosimendan affects oxidative and inflammatory pathways in the diaphragm of ventilated endotoxemic mice. Crit. Care, 19, 2015, 69.
83. [83] Doorduin, J., Sinderby, C.A., Beck, J., Stegeman, D.F., van Hees, H.W., van der Hoeven, J.G., Heunks, L.M., The calcium sensitizer levosimendan improves human diaphragm function. Am. J. Respir. Crit. Care Med. 185 (2012), 90–95.
84. [84] Roehl, A.B., Hein, M., Loetscher, P.D., Rossaint, J., Weis, J., Rossaint, R., Coburn, M., Neuroprotective properties of levosimendan in an in vitro model of traumatic brain injury. BMC Neurol., 10, 2010, 97.
85. [85] Hein, M., Zoremba, N., Bleilevens, C., Bruells, C., Rossaint, R., Roehl, A.B., Levosimendan limits reperfusion injury in a rat middle cerebral artery occlusion (MCAO) model. BMC Neurol., 13, 2013, 106.
86. [86] Katircioglu, S.F., Seren, M., Parlar, A.I., Turan, N.N., Manavbasi, Y., Aydog, G., Cicekcioglu, F., Tutun, U., Ulus, A.T., Levosimendan effect on spinal cord ischemia-reperfusion injury following aortic clamping. J. Card. Surg. 23 (2008), 44–48.
87. [87] Roehl, A.B., Zoremba, N., Kipp, M., Schiefer, J., Goetzenich, A., Bleilevens, C., Kuehn-Velten, N., Tolba, R., Rossaint, R., Hein, M., The effects of levosimendan on brain metabolism during initial recovery from global transient ischaemia/hypoxia. BMC Neurol., 12, 2012, 81.
88. [88] Bravo, M.C., López, P., Cabañas, F., Pérez-Rodríguez, J., Pérez-Fernández, E., Quero, J., Pellicer, A., Acute effects of levosimendan on cerebral and systemic perfusion and oxygenation in newborns: an observational study. Neonatology 99 (2011), 217–223.
89. [89] Kivikko, M., Kuoppamäki, M., Soinne, L., Sundberg, S., Pohjanjousi, P., Ellmen, J., Roine, R.O., Oral levosimendan increases cerebral blood flow velocities in patients with a history of stroke or transient ischemic attack: a pilot safety study. Curr. Ther. Res. Clin. Exp. 77 (2015), 46–51.
90. [90] Varvarousi, G., Xanthos, T., Sarafidou, P., Katsioula, E., Georgiadou, M., Eforakopoulou, M., Pavlou, H., Role of levosimendan in the management of subarachnoid hemorrhage. Am. J. Emerg. Med. 34 (2016), 298–306.
91. [91] Cengiz, S.L., Erdi, M.F., Tosun, M., Atalik, E., Avunduk, M.C., Sönmez, F.C., Mehmetoglu, I., Baysefer, A., Beneficial effects of levosimendan on cerebral vasospasm induced by subarachnoid haemorrhage: an experimental study. Brain Inj. 24 (2010), 877–885.
92. [92] Busani, S., Rinaldi, L., Severino, C., Cobelli, M., Pasetto, A., Girardis, M., Levosimendan in cardiac failure after subarachnoid hemorrhage. J. Trauma 68 (2010), E108–E110.
93. [93] Metra, M., Ponikowski, P., Dickstein, K., McMurray, J.J., Gavazzi, A., Bergh, C.H., Fraser, A.G., Jaarsma, T., Pitsis, A., Mohacsi, P., Böhm, M., Anker, S., Dargie, H., Brutsaert, D., Komajda, M., Heart Failure Association of the European Society of Cardiology. Advanced chronic heart failure: a position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology. Eur. J. Heart Fail. 9 (2007), 684–694.
94. [94] Nanas, J.N., Papazoglou, P., Tsagalou, E.P., Ntalianis, A., Tsolakis, E., Terrovitis, J.V., Kanakakis, J., Nanas, S.N., Alexopoulos, G.P., Anastasiou-Nana, M.I., Efficacy and safety of intermittent, long-term, concomitant dobutamine and levosimendan infusions in severe heart failure refractory to dobutamine alone. Am. J. Cardiol. 95 (2005), 768–771.
95. [95] Tuomainen, P.O., Magga, J., Timonen, P., Miettinen, K., Kurttila, M., Vanninen, E., Laitinen, T., Timonen, K., Punnonen, K., Parviainen, I., Uusaro, A., Vuolteenaho, O., Kivikko, M., Peuhkurinen, K., Intermittent levosimendan treatment in patients with severe congestive heart failure. Clin. Res. Cardiol. 102 (2013), 485–493.
96. [96] Malfatto, G., Della Rosa, F., Villani, A., Rella, V., Branzi, G., Facchini, M., Parati, G., Intermittent levosimendan infusions in advanced heart failure: favourable effects on left ventricular function, neurohormonal balance, and one-year survival. J. Cardiovasc. Pharmacol. 60 (2012), 450–455.
97. [97] Bonios, M.J., Terrovitis, J.V., Drakos, S.G., Katsaros, F., Pantsios, C., Nanas, S.N., Kanakakis, J., Alexopoulos, G., Toumanidis, S., Anastasiou-Nana, M., Nanas, J.N., Comparison of three different regimens of intermittent inotrope infusions for end stage heart failure. Int. J. Cardiol. 159 (2012), 225–229.
98. [98] Papadopoulou, E.F., Mavrogeni, S.I., Dritsas, A., Cokkinos, D.V., Assessment of quality of life using three activity questionnaires in heart failure patients after monthly, intermittent administration of levosimendan during a six-month period. Hell. J. Cardiol. 50 (2009), 269–274.
99. [99] Drakos, S.G., Kanakakis, J.V., Nanas, S., Bonios, M., Kaldara, E., Katsaros, F., Pantsios, C., Nanas, J.N., Intermittent inotropic infusions combined with prophylactic oral amiodarone for patients with decompensated end-stage heart failure. J. Cardiovasc. Pharmacol. 53 (2009), 157–161.
100. [100] Kleber, F.X., Bollmann, T., Borst, M.M., Costard-Jäckle, A., Ewert, R., Kivikko, M., Petterson, T., Pohjanjousi, P., Sonntag, S., Wikström, G., Repetitive dosing of intravenous levosimendan improves pulmonary hemodynamics in patients with pulmonary hypertension: results of a pilot study. J. Clin. Pharmacol. 49 (2009), 109–115.
101. [101] Parle, N.M., Thomas, M.D., Dembo, L., Best, M., Driscoll, G.O., Repeated infusions of levosimendan: well tolerated and improves functional capacity in decompensated heart failure — a single-centre experience. Heart Lung Circ. 17 (2008), 206–210.
102. [102] Mavrogeni, S., Giamouzis, G., Papadopoulou, E., Thomopoulou, S., Dritsas, A., Athanasopoulos, G., Adreanides, E., Vassiliadis, I., Spargias, K., Panagiotakos, D., Cokkinos, D.V., A 6-month follow-up of intermittent levosimendan administration effect on systolic function, specific activity questionnaire, and arrhythmia in advanced heart failure. J. Card. Fail. 13 (2007), 556–559.
103. [103] Silvetti, S., Nieminen, M.S., Repeated or intermittent levosimendan treatment in advanced heart failure: an updated meta-analysis. Int. J. Cardiol. 202 (2016), 138–143.
104. [104] Silvetti, S., Greco, T., Di Prima, A.L., Mucchetti, M., de Lurdes, C.M., Pasin, L., Scandroglio, M., Landoni, G., Zangrillo, A., Intermittent levosimendan improves mid-term survival in chronic heart failure patients: meta-analysis of randomised trials. Clin. Res. Cardiol. 103 (2014), 505–513.
105. [105] Altenberger, J., Parissis, J.T., Costard-Jaeckle, A., Winter, A., Ebner, C., Karavidas, A., Sihorsch, K., Avgeropoulou, E., Weber, T., Dimopoulos, L., Ulmer, H., Poelzl, G., Efficacy and safety of the pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep) study: a multicentre randomized trial. Eur. J. Heart Fail. 16 (2014), 898–906.
106. [106] Nieminen MS, Altenberger J, Ben-Gal T, Böhmer A, Comin-Colet J, Dickstein K, Edes I, Fedele F, Fonseca C, García-González MJ1, Giannakoulas G, Iakobishvili Z, Jääskeläinen P, Karavidas A, Kettner J, Kivikko M, Lund LH, Matskeplishvili ST, Metra M, Morandi F, Oliva F, Parkhomenko A, Parissis J, Pollesello P, Pölzl G, Schwinger RH, Segovia J, Seidel M, Vrtovec B, Wikström G. Repetitive use of levosimendan for treatment of chronic advanced heart failure: clinical evidence, practical considerations, and perspectives: an expert panel consensus. Int. J. Cardiol. 2014;174:360–7.
107. [107] Tsao, C.M., Li, K.Y., Chen, S.J., Ka, S.M., Liaw, W.J., Huang, H.C., Wu, C.C., Levosimendan attenuates multiple organ injury and improves survival in peritonitis-induced septic shock: studies in a rat model. Crit. Care, 18, 2014, 652.
108. [108] Barraud, D., Faivre, V., Damy, T., Welschbillig, S., Gayat, E., Heymes, C., Payen, D., Shah, A.M., Mebazaa, A., Levosimendan restores both systolic and diastolic cardiac performance in lipopolysaccharide-treated rabbits: comparison with dobutamine and milrinone. Crit. Care Med. 35 (2007), 1376–1382.
109. [109] Ji, M., Li, R., Li, G.M., Fan, Y., Dong, L., Yang, J., Peng, Y.G., Wu, J., Effects of combined levosimendan and vasopressin on pulmonary function in porcine septic shock. Inflammation 35 (2012), 871–880.
110. [110] Dubin, A., Maskin, B., Murias, G., Pozo, M.O., Sottile, J.P., Barán, M., Edul, V.S., Canales, H.S., Estenssoro, E., Effects of levosimendan in normodynamic endotoxaemia: a controlled experimental study. Resuscitation 69 (2006), 277–286.
111. [111] Wang, Q., Yokoo, H., Takashina, M., Sakata, K., Ohashi, W., Abedelzaher, L.A., Imaizumi, T., Sakamoto, T., Hattori, K., Matsuda, N., Hattori, Y., Anti-inflammatory profile of levosimendan in cecal ligation-induced septic mice and in lipopolysaccharide-stimulated macrophages. Crit. Care Med. 43 (2015), e508–e520.
112. [112] Sareila, O., Korhonen, R., Auvinen, H., Hämäläinen, M., Kankaanranta, H., Nissinen, E., Moilanen, E., Effects of levo- and dextrosimendan on NF-kappaB-mediated transcription, iNOS expression and NO production in response to inflammatory stimuli. Br. J. Pharmacol. 155 (2008), 884–895.
113. [113] Zangrillo, A., Putzu, A., Monaco, F., Oriani, A., Frau, G., De Luca, M., Di Tomasso, N., Bignami, E., Lomivorotov, V., Likhvantsev, V., Landoni, G., Levosimendan reduces mortality in patients with severe sepsis and septic shock: a meta-analysis of randomized trials. J. Crit. Care 30 (2015), 908–913.
114. [114] Morelli, A., De Castro, S., Teboul, J.L., Singer, M., Rocco, M., Conti, G., De Luca, L., Di Angelantonio, E., Orecchioni, A., Pandian, N.G., Pietropaoli, P., Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression. Intensive Care Med. 31 (2005), 638–644.
115. [115] Morelli, A., Donati, A., Ertmer, C., Rehberg, S., Lange, M., Orecchioni, A., Cecchini, V., Landoni, G., Pelaia, P., Pietropaoli, P., Van Aken, H., Teboul, J.L., Ince, C., Westphal, M., Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study. Crit. Care, 14, 2010, R232.
116. [116] Torraco, A., Carrozzo, R., Piemonte, F., Pastore, A., Tozzi, G., Verrigni, D., Assenza, M., Orecchioni, A., D'Egidio, A., Marraffa, E., Landoni, G., Bertini, E., Morelli, A., Effects of levosimendan on mitochondrial function in patients with septic shock: a randomized trial. Biochimie 102 (2014), 166–173.
117. [117] Orme, R.M., Perkins, G.D., McAuley, D.F., Liu, K.D., Mason, A.J., Morelli, A., Singer, M., Ashby, D., Gordon, A.C., An efficacy and mechanism evaluation study of Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS): protocol for a randomized controlled trial. Trials, 15, 2014, 199.
118. [118] Lomivorotov, V.V., Boboshko, V.A., Efremov, S.M., Kornilov, I.A., Chernyavskiy, A.M., Lomivorotov, V.N., Knazkova, L.G., Karaskov, A.M., Levosimendan versus an intra-aortic balloon pump in high-risk cardiac patients. J. Cardiothorac. Vasc. Anesth. 26 (2012), 596–603.
119. [119] Leppikangas, H., Järvelä, K., Sisto, T., Maaranen, P., Virtanen, M., Lehto, P., Karlsson, S., Kööbi, T., Lindgren, L., Preoperative levosimendan infusion in combined aortic valve and coronary bypass surgery. Br. J. Anaesth. 106 (2011 Mar), 298–304.
120. [120] Di Chiara, L., Ricci, Z., Garisto, C., Morelli, S., Giorni, C., Vitale, V., Di Donato, R.M., Picardo, S., Initial experience with levosimendan infusion for preoperative management of hypoplastic left heart syndrome. Pediatr. Cardiol. 31 (2010), 166–167.
121. [121] De Hert, S.G., Lorsomradee, S., vanden Eede, H., Cromheecke, S., Van der Linden, P.J., A randomized trial evaluating different modalities of levosimendan administration in cardiac surgery patients with myocardial dysfunction. J. Cardiothorac. Vasc. Anesth. 22 (2008), 699–705.
122. [122] De Hert, S.G., Lorsomradee, S., Cromheecke, S., Van der Linden, P.J., The effects of levosimendan in cardiac surgery patients with poor left ventricular function. Anesth. Analg. 104 (2007 Apr), 766–773.
123. [123] Barisin, S., Husedzinovic, I., Sonicki, Z., Bradic, N., Barisin, A., Tonkovic, D., Levosimendan in off-pump coronary artery bypass: a four-times masked controlled study. J. Cardiovasc. Pharmacol. 44 (2004), 703–708.
124. [124] Tasouli, A., Papadopoulos, K., Antoniou, T., Kriaras, I., Stavridis, G., Degiannis, D., Geroulanos, S., Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use. Eur. J. Cardiothorac. Surg. 32 (2007), 629–633.
125. [125] Toller, W., Heringlake, M., Guarracino, F., Algotsson, L., Alvarez, J., Argyriadou, H., Ben-Gal, T., Černý, V., Cholley, B., Eremenko, A., Guerrero-Orriach, J.L., Järvelä, K., Karanovic, N., Kivikko, M., Lahtinen, P., Lomivorotov, V., Mehta, R.H., Mušič, Š., Pollesello, P., Rex, S., Riha, H., Rudiger, A., Salmenperä, M., Szudi, L., Tritapepe, L., Wyncoll, D., Öwall, A., Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion. Int. J. Cardiol. 184 (2015), 323–336.
126. [126] Morelli, A., Ertmer, C., Pietropaoli, P., Westphal, M., Reducing the risk of major elective non-cardiac surgery: is there a role for levosimendan in the preoperative optimization of cardiac function?. Curr. Drug Targets 10 (2009), 863–871.
127. [127] Fournell, A., Scheeren, T.W., Picker, O., Schwarte, L.A., Pharmacologic interventions to improve splanchnic oxygenation during ventilation with positive end-expiratory pressure. Adv. Exp. Med. Biol. 737 (2012), 235–238.
128. [128] Farmakis, D., Stafylas, P., Giamouzis, G., Maniadakis, N., Parissis, J., The medical and socioeconomic burden of heart failure: a comparative delineation with cancer. Int. J. Cardiol. 203 (2016), 279–281.
129. [129] Feltracco, P., Carollo, C., Ori, C., Levosimendan in lung transplant recipients with difficult weaning from ECMO. Minerva Anestesiol. 81 (2015), 92–93.
130. [130] Affronti, A., di Bella, I., Carino, D., Ragni, T., Levosimendan may improve weaning outcomes in venoarterial ECMO patients. ASAIO J. 59 (2013), 554–557.
131. [131] Eriksson, H.I., Jalonen, J.R., Heikkinen, L.O., Kivikko, M., Laine, M., Leino, K.A., Kuitunen, A.H., Kuttila, K.T., Peräkylä, T.K., Sarapohja, T., Suojaranta-Ylinen, R.T., Valtonen, M., Salmenperä, M.T., Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function. Ann. Thorac. Surg. 87 (2009), 448–454.
132. [132] Papanikolaou, J., Tsolaki, V., Makris, D., Zakynthinos, E., Early levosimendan administration may improve outcome in patients with subarachnoid hemorrhage complicated by acute heart failure. Int. J. Cardiol. 176 (2014), 1435–1437.
133. [133] Taccone, F.S., Brasseur, A., Vincent, J.L., De Backer, D., Levosimendan for the treatment of subarachnoid hemorrhage-related cardiogenic shock. Intensive Care Med. 39 (2013), 1497–1498.