Cardiovascular Drugs and Therapy

, Volume 17, Issue 2, pp 111–113 | Cite as

Vasodilating Mechanisms of Levosimendan

Editorial Board


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  1. 1.
    Pollesello P, Ovaska M, Kaivola J, et al. Binding of a new Ca2+ sensitizer, levosimendan, to recombinant human cardiac troponin C. A molecular modelling, fluorescence probe, and proton nuclear magnetic resonance study. J Biol Chem 1994;269:28584-28590.Google Scholar
  2. 2.
    Haikala H, Kaivola J, Nissinen E, Wall P, Levijoki J, Linden IB. Cardiac troponin C as a target protein for a novel calcium sensitizing drug, levosimendan. J Mol Cell Cardiol 1995;27:1859-1866.Google Scholar
  3. 3.
    Haikala H, Nissinen E, Etemadzadeh E, Levijoki J, Linden IB. Troponin. C-mediated calcium sensitization induced by levosimendan does not impair relaxation. J Cardiovasc Pharmacol 1995;25:794-801.Google Scholar
  4. 4.
    Edes I, Kiss E, Kitada Y, et al. Effects of levosimendan, a cardiotonic agent targeted to troponin C, on cardiac function and on phosphorylation and Ca2+ sensitivity of cardiac myofibrils and sarcoplasmic reticulum in guinea pig heart. Circ Res 1995;77:107-113.Google Scholar
  5. 5.
    Nijhawan N, Nicolosi AC, Montgomery MW, Aggarwal A, Pagel PS, Warltier DC. Levosimendan enhances cardiac performance after cardiopulmonary bypass: Aprospective, randomized placebo-controlled trial. J Cardiovasc Pharmacol 1999;34:219-228.Google Scholar
  6. 6.
    Slawsky MT, Colucci WS, Gottlieb SS, et al. Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Circulation 2000;102:2222-2227.Google Scholar
  7. 7.
    Follath F, Cleland JG, Just H, et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): A randomised double-blind trial. Lancet 2002;360:196-202.Google Scholar
  8. 8.
    Moiseyev VS, Poder P, Andrejevs N, et al. Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN). Eur Heart J 2002;23:1422-1432.Google Scholar
  9. 9.
    Rump AF, Acar D, Klaus W. A quantitative comparison of functional and anti-ischaemic effects of the phosphodiesterase-inhibitors, amrinone, milrinone and levosimendan in rabbit isolated hearts. Br J Pharmacol 1994;112:757-762.Google Scholar
  10. 10.
    Lilleberg J, Nieminen MS, Akkila J, et al. Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting. Eur Heart J 1998;19:660-668.Google Scholar
  11. 11.
    Gruhn N, Nielsen-Kudsk JE, Theilgaard S, Bang L, Olesen SP, Aldershvile J. Coronary vasorelaxant effect Vasodilating Mechanisms of Levosimendan 113 of levosimendan, a new inodilator with calcium-sensitizing properties. J Cardiovasc Pharmacol 1998;31:741-749.Google Scholar
  12. 12.
    Haikala H, Kaheinen P, Levijoki J, Linden IB. The role of cAMP-and cGMP-dependent protein kinases in the cardiac actions of the new calcium sensitizer, levosimendan. Cardiovasc Res 1997;34:536-546.Google Scholar
  13. 13.
    Bowman P, Haikala H, Paul RJ. Levosimendan, a calcium sensitizer in cardiac muscle, induces relaxation in coronary smooth muscle through calcium desensitization. J Pharmacol Exp Ther 1999;288:316-325.Google Scholar
  14. 14.
    Yokoshiki H, Katsube Y, Sunagawa M, Sperelakis N. Levosimendan, a novel Ca2+ sensitizer, activates the glibenclamide-sensitiveK+ channel in rat arterial myocytes. Eur J Pharmacol 1997;333:249-259.Google Scholar
  15. 15.
    Pataricza J, Hohn J, Petri A, Balogh A, Papp JG. Comparison of the vasorelaxing effect of cromakalim and the new inodilator, levosimendan, in human isolated portal vein. J Pharm Pharmacol 2000;52:213-217.Google Scholar
  16. 16.
    De Witt BJ, Ibrahim IN, Bayer E, et al. An analysis of responses to levosimendan in the pulmonary vascular bed of the cat. Anesth Analg 2002;94:1427-1433.Google Scholar
  17. 17.
    Kersten JR, Montgomery MW, Pagel PS, Warltier DC. Levosimendan, a new positive inotropic drug, decreases myocardial infarct size via activation of K(ATP) channels. Anesth Analg 2000;90:5-11.Google Scholar
  18. 18.
    Kaheinen P, Pollesello P, Levijoki J, Haikala H. Levosimendan increases diastolic coronary flow in isolated guinea-pig heart by opening ATP-sensitive potassium channels. J Cardiovasc Pharmacol 2001;37:367-374.Google Scholar
  19. 19.
    Quast U. Do the K+ channel openers relax smooth muscle by opening K+ channels? Trends Pharmacol Sci 1993;14:332-337.Google Scholar
  20. 20.
    Koppel H, Holzmann S, Pilger E, Klein W, Gasser R. Minimal effects of levosimendan on coronary artery smooth muscle tone. Cardiovasc Drugs Ther 1999;13:357-358.Google Scholar
  21. 21.
    Krassoi I, Pataricza J, Kun A, Papp JG. Calcium-dependent vasorelaxant capacity of levosimendan in porcine and human epicardial coronary artery preparations. Cardiovasc Drugs Ther 2000;14:691-693.Google Scholar
  22. 22.
    Pataricza J, Krassói I, Hôhn J, Kun A, Papp JG. Functional role of potassium channels in the vasodilating mechanism of levosimendan in porcine isolated coronary artery. Cardiovasc Drugs Ther 2003 (in press).Google Scholar
  23. 23.
    Nelson MT, Quayle JM. Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol 1995;268:C799-822.Google Scholar
  24. 24.
    Harder DR, Belardinelli L, Sperelakis N, Rubio R, Berne RM. Differential effects of adenosine and nitroglycerin on the action potentials of large and small coronary arteries. Circ Res 1979;44:176-182.Google Scholar
  25. 25.
    Sato K, Kanatsuka H, Sekiguchi N, et al. Effect of an ATP sensitive potassium channel opener, levcromakalim, on coronary arterial microvessels in the beating canine heart. Cardiovasc Res 1994;28:1780-1786.Google Scholar
  26. 26.
    Shimizu S, Yokoshiki H, Sperelakis N, Paul RJ. Role of voltage-dependent and Ca(2+)-activated K(+) channels on the regulation of isometric force in porcine coronary artery. J Vasc Res 2000;37:16-25.Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  1. 1.Department of Cardiovascular MedicineHokkaido University Graduate School of Medicine, SapporoJapan
  2. 2.Department of Molecular and Cellular PhysiologyUniversity of Cincinnati, College of MedicineCincinnatiUSA

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