Плейотропные эффекты левосимендана на сердце и другие органы


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Аннотация


Левосимендан — негликозидное кардиотоническое лекарственное средство, обладающее вазодилатирующими свойствами. К основным механизмам действия препарата относят увеличение чувствительности сократительных белков кардиомиоцитов к кальцию и способность открывать аденозинтрифосфат-зависимые калиевые каналы в гладких мышцах сосудистой стенки. В соответствии с настоящими рекомендациями Европейского общества кардиологов, показанием к использованию левосимендана является лечение острой декомпенсации тяжелой хронической сердечной недостаточности. С момента первого применения препарата (более 15 лет назад) обнаружен ряд дополнительных плейотропных эффектов, которые не только оказывают влияние на состояние миокарда (при ишемии и ремоделировании), но и потенцируют органопротективные процессы за пределами сердечно-сосудистой системы. В ходе экспериментальных и клинических исследований были выявлены механизмы, оказывающие положительное влияние на функцию легких, почек, печени, органов желудочно-кишечного тракта, центральной нервной системы, а также на процессы воспаления и сепсиса. В данной обзорной статье обобщены существующие исследования и доказательства плейотропных эффектов левосимендана, а также показаны потенциальные новые области его клинического применения.

Поступила в редакцию 3 апреля 2017 г. Принята к печати 30 мая 2016 г.

Финансирование
Исследование не имело спонсорской поддержки.
Конфликт интересов
Авторы заявляют об отсутствии конфликта интересов.


В. В. Ломиворотов
http://orcid.org/0000-0001-8591-6461
ФГБУ «Сибирский федеральный биомедицинский исследовательский центр имени академика Е.Н. Мешалкина», Министерство здравоохранения Российской Федерации, Новосибирск, Российская Федерация

В. А. Бобошко
http://orcid.org/0000-0001-5420-2263
ФГБУ «Сибирский федеральный биомедицинский исследовательский центр имени академика Е.Н. Мешалкина», Министерство здравоохранения Российской Федерации, Новосибирск, Российская Федерация

Для корреспонденции: Бобошко Владимир Александрович, v_boboshko@meshalkin.ru

Литература


  1. Pollesello P., Papp Z., Papp J.G. Calcium sensitizers: what have we learned over the last 25 years? Int J Cardiol. 2016;203:543-8. http://dx.doi.org/10.1016/j.ijcard.2015.10.240
  2. 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. 1995;27(9):1859-66.
  3. 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. 1998;98(20):2141-7.
  4. 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. 1997;29(5):563-73.
  5. 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. 2005;288(2):H914-22. https://doi.org/10.1152/ajpheart.00465.2004
  6. Brixius K., Reicke S., Schwinger R.H. Beneficial effects of the Ca(2+) sensitize levosimendan in human myocardium. Am J Physiol Heart Circ Physiol. 2002;282(1):H131-7.
  7. Givertz M.M., Andreou C., Conrad C.H., Colucci W.S. Direct myocardial effects of levosimendan in humans with left ventricular dysfunction: alteration of forcefrequency and relaxation-frequency relationships. Circulation. 2007;115(10):1218-24. https://doi.org/10.1161/CIRCULATIONAHA.106.668640
  8. Parissis J.T., Panou F., Farmakis D., Adamopoulos S., Filippatos G., Paraskevaidis I., Venetsanou K., Lekakis J., Kremastinos D.T. Effects of levosimendan onmarkers of left ventricular diastolic function and neurohormonal activation in patients with advanced heart failure. Am J Cardiol. 2005;96(3):423-6. https://doi.org/10.1016/j.amjcard.2005.03.092
  9. 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. 2015;66(2):141-7. https://doi.org/10.1097/FJC.0000000000000256
  10. Jörgensen K., Bech-Hanssen O., Houltz E., Ricksten S.E. Effects of levosimendan on left ventricular relaxation and early filling atmaintained preload and afterload conditions after aortic valve replacement for aortic stenosis. Circulation. 2008;117(8):1075-81. https://doi.org/10.1161/CIRCULATIONAHA.107.722868 
  11. 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. 1996;91(4):296-307.
  12. 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. 2007;35(3):707-15. https://doi.org/10.1097/01.CCM.0000257326.96342.57
  13. 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. 2007;51(9):1217-24. https://doi.org/10.1111/j.1399-6576.2007.01428.x
  14. 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. 2009;60(3):41-7.
  15. 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. 2011;109(5):387-97. https://doi.org/10.1111/j.1742-7843.2011.00743.x
  16. Okada M., Suzuki A., Yamawaki H., Hara Y. Levosimendaninhibitsinterleukin-1β- induced cell migration and MMP-9 secretion in rat cardiac fibroblasts. Eur J Pharmacol. 2013;718(1-3):332-9. https://doi.org/10.1016/j.ejphar.2013.08.013
  17. 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. 2005;19(6):399-402. https://doi.org/10.1007/s10557-005-5417-5
  18. 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. 2007;9(6-7):684-94. https://doi.org/10.1016/j.ejheart.2007.04.003
  19. 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. 2013;102(7):485-93. https://doi.org/10.1007/s00392-013-0554-5
  20. 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. 2012;60(5):450-5. https://doi.org/10.1097/FJC.0b013e31826b86aa
  21. 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 midterm survival in chronic heart failure patients: meta-analysis of randomised trials. Clin Res Cardiol. 2014;103(7):505-13. https://doi.org/10.1007/s00392-013-0649-z 
  22. 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. 2014;16(8):898-906. https://doi.org/10.1002/ejhf.118 
  23. Nieminen M.S., Altenberger J., Ben-Gal T., Böhmer A., Comin-Colet J., Dickstein K., Edes I., Fedele F., Fonseca C., García-González M.J., Giannakoulas G., Iakobishvili Z., Jääskeläinen P., Karavidas A., Kettner J., Kivikko M., Lund L.H., Matskeplishvili S.T., Metra M., Morandi F., Oliva F., Parkhomenko A., Parissis J., Pollesello P., Pölzl G., Schwinger R.H., 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(2):360-7. https://doi.org/10.1016/j.ijcard.2014.04.111
  24. Pollesello P., Papp Z. The cardioprotective effects of levosimendan: preclinical and clinical evidence. J Cardiovasc Pharmacol. 2007;50(3):257-63. https://doi.org/10.1097/FJC.0b013e3180986230
  25. 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. 2010;105(2):155-67. https://doi.org/10.1007/s00395-009-0064-9 
  26. 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. 2010;54(1):103-10. https://doi.org/10.1111/j.1399-6576.2009.02070.x 
  27. 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. 2007;47(4):248-56. https://doi.org/10.1016/j.vph.2007.06.008 
  28. 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. 2008;154(1):41-50. https://doi.org/10.1038/bjp.2008.52
  29. 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. 2006;96(6):694-700. https://doi.org/10.1093/bja/ael082
  30. 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. 2004;43(12):2177-82. https://doi.org/10.1016/j.jacc.2004.02.052
  31. 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. 2006;19(2):172-7. https://doi.org/10.1016/j.echo.2005.08.016
  32. 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. 2009;156(2):250-61. https://doi.org/10.1111/j.1476-5381.2008.00024.x
  33. 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. 2012;110(3):269-74. https://doi.org/10.1111/j.1742-7843.2011.00801.x
  34. Greenberg G., Cohen E., Garty M., Iakobishvili Z., Sandach A., Behar S. Outcomes of acute heart failure associated with acute coronary syndrome versus other causes. Acute Card Care. 2011;13(2):87-92. https://doi.org/10.3109/17482941.2011.567284 
  35. Moiseyev V.S., Põder P., Andrejevs N., Ruda M.Y., Golikov A.P., Lazebnik L.B. 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(18):1422-32.
  36. Husebye T., Eritsland J., Müller C., Sandvik L., Arnesen H., Seljeflot I. Levosimendan in acute heart failure following primary percutaneous coronary intervention-treated acute ST-elevation myocardial infarction. Results from the LEAF trial: a randomized, placebo-controlled study. Eur J Heart Fail. 2013;15(5):565-72. https://doi.org/10.1093/eurjhf/hfs215
  37. Wu X., Wu J., Yan X., Zhang Y. Enhancement of myocardial function and reduction of injury with levosimendan after percutaneous coronary intervention for acute myocardial infarction: a pilot study. Cardiology. 2013;15(5):565-72. https://doi.org/10.1093/eurjhf/hfs215
  38. Mebazaa A., Nieminen M.S., Packer M., Cohen-Solal A., Kleber F.X., Pocock S.J. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007;297(17):1883-91. https://doi.org/10.1001/jama.297.17.1883 
  39. Dominguez-Rodriguez A., Samimi-Fard S., Garcia-Gonzalez M.J., Abreu-Gonzalez P. Effects of levosimendan versus dobutamine on left ventricular diastolic function in patients with cardiogenic shock after primary angioplasty. Int J Cardiol. 2008;128(2):214-7.
  40. Landoni G., Biondi-Zoccai G., Greco M., Greco T., Bignami E., Morelli A. Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies. Crit Care Med. 2012;40(2):634-46. https://doi.org/10.1097/CCM.0b013e318232962a
  41. Koster G., Wetterslev J., Gluud C., Zijlstra J.G., Scheeren T.W., van der Horst I.C. Effects of levosimendan for low cardiac output syndrome in critically ill patients: systematic review with meta-analysis and trial sequential analysis. Intensive Care Med. 2015;41(2):203-21. https://doi.org/10.1007/s00134-014-3604-1
  42. Nieminen M.S., Buerke M., Cohen-Solál A., Costa S., Édes I., Erlikh A., Franco F., Gibson C., Gorjup V., Guarracino F., Gustafsson F., Harjola V.P., Husebye T., Karason K., Katsytadze I., Kaul S., Kivikko M., Marenzi G., Masip J., Matskeplishvili S., Mebazaa A., Møller J.E., Nessler J., Nessler B., Ntalianis A., Oliva F., Pichler-Cetin E., Põder P., Recio-Mayoral A., Rex S., Rokyta R., Strasser R.H., Zima E., Pollesello P. The role of levosimendan in acute heart failure complicating acute coronary syndrome: A review and expert consensus opinion. Int J Cardiol. 2016;218:150-7. https://doi.org/10.1016/j.ijcard.2016.05.009
  43. 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. 2011;19(2):154-9. https://doi.org/10.1177/0218492311401143
  44. 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. 2015;184:323-36. https://doi.org/10.1016/j.ijcard.2015.02.022
  45. 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. 2009;10(9):863-71.
  46. Чернявский А.М., Несмачный А.С., Рузматов Т.М., Бобошко А.В., Николаев Д.А., Бобошко В.А., Эфендиев В.У., Подсосникова Т.Н. Хирургическое лечение ишемической болезни сердца у пациентов с низкой фракцией выброса левого желудочка на работающем сердце в условиях искусственного кровообращения: непосредственные результаты. Патология кровообращения и кардиохирургия. 2015;19(1):51-8. http://dx.doi.org/10.21688/1681-3472-2015-1-51-58 [Chernyavskiy A.M., Nesmachnyy A.S., Ruzmatov T.M., Boboshko A.V., Nikolaev D.A., Boboshko V.A., Efendiev V.U., Podsosnikova T.N. Surgical on-pump beating-heart treatment of ischemic patients with low LF ejection fraction: immediate results. Patologiya krovoobrashcheniya i kardiokhirurgiya = Circulation Pathology and Cardiac Surgery. 2015;19(1):51-58. (In Russ.) http://dx.doi.org/10.21688/1681-3472-2015-1-51-58]
  47. 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. 2012;342(2):376-88. http://dx.doi.org/10.1124/jpet.112.193961
  48. 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. 2014;30:47–51. http://dx.doi.org/10.1177/0748233712451773
  49. 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. 2006;290(6):F1453-62. http://dx.doi.org/10.1152/ajprenal.00485.2005
  50. 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. 2013;41(10):2328-35. http://dx.doi.org/10.1097/CCM.0b013e31828e946a 
  51. 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. 2014;28(3):586-94. http://dx.doi.org/10.1053/j.jvca.2013.09.004 
  52. 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. 2014;16(3):281-8. http://dx.doi.org/10.1002/ejhf.9
  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. 2014;63(2):107-12. http://dx.doi.org/10.1097/FJC.0000000000000028 
  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. 2016;67(3):408-16. http://dx.doi.org/10.1053/j.ajkd.2015.09.015
  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 V., Calabrò M.G. 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. 2015;7(1):35-4.
  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. 2007;21(6):431-5. http://dx.doi.org/10.1007/s10557-007-6066-7
  57. 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). 2015. http://dx.doi.org/10.2459/JCM.0000000000000244
  58. 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. 2014;20(3):361-75. http://dx.doi.org/10.1002/lt.23799
  59. 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. 1996;119(3):609-15.
  60. 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. 2010;34(3):275-80. http://dx.doi.org/10.1097/SHK.0b013e3181cd8c5b 
  61. 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. 2013;41(6):719-27. 
  62. 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. 2005;33(1):135-42;discussion 246-7.
  63. 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. 2009;109(5):1568-75. http://dx.doi.org/10.1213/ane.0b013e3181af3fe3
  64. 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. 2008;52(6):785-92. http://dx.doi.org/10.1111/j.1399-6576.2008.01659.x 
  65. 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. 2015;10(1):e0114963. http://dx.doi.org/10.1371/journal.pone.0114963 
  66. 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. 2013;8(6):e66195. http://dx.doi.org/10.1371/journal.pone.0066195 
  67. 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. 2006;34(9):2287-93. http://dx.doi.org/10.1097/01.CCM.0000230244.17174.4F 
  68. 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. 2005;172(2):200-5. http://dx.doi.org/10.1164/rccm.200502-262OC
  69. 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. 2009;179(1):41-7. http://dx.doi.org/10.1164/rccm.200805-732OC 
  70. 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 path- ways in the diaphragm of ventilated endotoxemic mice. Crit Care. 2015;19:69. http://dx.doi.org/10.1186/s13054-015-0798-8
  71. 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. 2012;185(1):90-5. http://dx.doi.org/10.1164/rccm.201107-1268OC
  72. 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. 2012;737:235-8. http://dx.doi.org/10.1007/978-1-4614-1566-4_34
  73. Affronti A., di Bella I., Carino D., Ragni T. Levosimendan may improve weaning outcomes in venoarterial ECMO patients. ASAIO J. 2013;59(6):554-7. http://dx.doi.org/10.1097/MAT.0b013e3182a4b32e 
  74. 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. 2009;87(2):448-54. http://dx.doi.org/10.1016/j.athoracsur.2008.10.029
  75. 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. 2010;10:97. http://dx.doi.org/10.1186/1471-2377-10-97 
  76. 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. 2013;13:106. http://dx.doi.org/10.1186/1471-2377-13-106
  77. 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. 2008;23(1):44-8. http://dx.doi.org/10.1111/j.1540-8191.2007.00486.x 
  78. 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. 2012;12:81. http://dx.doi.org/10.1186/1471-2377-12-81 
  79. 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 ox- ygenation in newborns: an observational study. Neonatology. 2011;99(3):217-23. http://dx.doi.org/10.1159/000314955 
  80. 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. 2015;77:46-51. http://dx.doi.org/10.1016/j.curtheres.2015.01.001 
  81. 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. 2016;34(2):298-306. http://dx.doi.org/10.1016/j.ajem.2015.11.024
  82. 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. 2010;24(6):877-85. http://dx.doi.org/10.3109/02699051003789260 
  83. Busani S., Rinaldi L., Severino C., Cobelli M., Pasetto A., Girardis M. Levosimendan in cardiac failure after subarachnoid hemorrhage. J Trauma. 2010;68(5):E108-10. http://dx.doi.org/10.1097/TA.0b013e31817c4284
  84. 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. 2008;197(1):278-82.
  85. 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. 2015;113(2):350-62. http://dx.doi.org/10.1160/TH14-06-0549 
  86. 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. 2011;15(4):R166. http://dx.doi.org/10.1186/cc10307. 
  87. 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. 2006 Dec;8(8):804-9. http://dx.doi.org/10.1016/j.ejheart.2006.03.003
  88. 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. 2014;18(6):652. http://dx.doi.org/10.1186/s13054-014-0652-4
  89. 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 pro- file of levosimendan in cecal ligation-induced septic mice and in lipopolysaccha-ride-stimulated macrophages. Crit Care Med. 2015;43(11):e508-20. http://dx.doi.org/10.1097/CCM.0000000000001269
  90. 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. 2015;30(5):908-13. http://dx.doi.org/10.1016/j.jcrc.2015.05.017
  91. 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. 2005;31(5):638-44. http://dx.doi.org/10.1007/s00134-005-2619-z
  92. 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. 2010;14(6):R232. http://dx.doi.org/10.1186/cc9387
  93. 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. 2014;102:166-73. http://dx.doi.org/10.1016/j.biochi.2014.03.006 
  94. Gordon A.C., Perkins G.D., Singer M., McAuley D.F., Orme R.M., Santhakumaran S., Mason A.J., Cross M., Al-Beidh F., Best-Lane J., Brealey D., Nutt C.L., McNamee J.J., Reschreiter H., Breen A., Liu K.D., Ashby D. Levosimendan for the prevention of acute organ dysfunction in sepsis. N Engl J Med. 2016;375(17):1638-1648. http://dx.doi.org/10.1056/NEJMoa1609409

Ломиворотов В. В., Бобошко В. А. Плейотропные эффекты левосимендана на сердце и другие органы. Патология кровообращения и кардиохирургия. 2017;21(2):14-28. http://dx.doi.org/10.21688/1681-3472-2017-2-14-28


DOI: http://dx.doi.org/10.21688/1681-3472-2017-2-14-28

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