A study of myocardial contractile function and injury degree on a model of isolated rat heart subjected to four-hour car-dioplegic ischemia and reperfusion under conditions of postconditioning by levosimendan

A widespread introduction of cardiac transplantation methods into cardiological practice and increase in a number of cardiopulmonary bypass surgical interferences determine the necessity of improvement of myocardial protection methods from ischemic and reperfusion injuries. Myocardial contractile function and injury degree were studied on a model of isolated rat heart subjected to four-hour pharmaco-hypothermic cardioplegia and reperfusion under conditions of cardioprotection by levosimendan. The presence of cardioprotective effect of postconditioning by levosimendan in regard to an isolated heart in reperfusion period of four-hour cardioplegic ischemia was found out. The given effect was manifested in reducing of reperfusion ejection of myocardial injury enzymatic markers and a complete restoration of contractive activity parameters of isolated hearts in reperfusion period.

изолированное сердце, фармакохолодовая кардиоплегия, реперфузия, левосимендан, фармакологическое посткондиционирование, isolated heart, pharmaco-hypothermic cardioplegia, reperfusion, levosimendan, pharmacological postconditioning

1. Писаренко ОИ, Шульженко ВС, Студнева ИМ. Улучшение восстановления функции изолированного сердца модифицированным реперфузионным раствором. Кардиология. 2005;45(7):38-43.

2. Шляхто ЕВ, Галагудза ММ, Сыренский АВ. и др. Ишемическое посткондиционирование миокарда: новый способ защиты сердца от реперфузионного повреждения. Терапевтический архив. 2005;77(5):77-80.

3. Cohen MV, Yang XM, Downey JM. The pH hypothesis of postconditioning: staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis. Circulation. 2007;115 (14):1895-1903.

4. Наумов АБ, Баутин АЕ, Кутин АМ и др. Применение левосимендана для лечения кардиогенного шока, связанного с развитием острой правожелудочковой недостаточности после аортокоронарного шунтирования. Кардиология и сердечно-сосудистая хирургия. 2009;49(1):79-81.

5. Kolseth SM, Rolim NP, Salvesen O, Nordhaug DO, Wahba A, Hoydal MA. Levosimendan improves contractility in vivo and in vitro in a rodent model of post-myocardial infarction heart failure. Acta Physiol (Oxf). 2014;210(4):865-874. doi: 10.1111/apha.12248.

6. Lepran I, Pollesello P, Vajda S, Varró A, Papp JG. Preconditioning Effects of Levosimendan in a Rabbit Cardiac Ischemia-Reperfusion Model. J Cardiovasc Pharmacol. 2006;48 (4):148-152.

7. Hönisch A, Theuring N, Ebner B, Wagner C, Strasser RH, 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):155-167. doi: 10.1007/s00395-009-0064-9.

8. Kaheinen P1, Pollesello P, Levijoki J, Haikala H. Levosim endan Increases Diastolic Coronary Flow in Isolated Guinea-Pig Heart by Opening ATP-Sensitive Potassium Channels. J Cardiovasc Pharmacol. 2001;37(4):367-74.

9. Uberti F, Caimmi PP, Molinari C, Mary D, Vacca G, Grossini E. Levosimendan Modulates Programmed Forms of Cell Death Through KATP Channels and Nitric Oxide. J Cardiovasc Pharmacol. 2011;57(2):246-258. doi:10.1097/ FJC.0b013e318204bb55.

10. Минасян СМ, Галагудза ММ, Дмитриев ЮВ и др. Консервация донорского сердца: история и современность с позиции трансляционной медицины. Регионарное кровообращение и микроциркуляция. 2014;13(3):4-16.

11. Минасян СМ, Галагудза ММ, Сонин ДЛ и др. Методика перфузии изолированного сердца крысы. Регионарное кровообращение и микроциркуляция. 2010;8(4):54-59.

12. Sutherland FJ, Shattock MJ, Baker KE, Hearse DJ. Mouse isolated perfused heart: characteristics and cautions. Clin Exp Pharmacol Physiol. 2003;30(11):867-878.

13. Ozturk T, Gok S, Nese N. Levosimendan attenuates reperfusion injury in an isolated perfused rat heart model. J Cardiothorac Vasc Anesth. 2010;24(4):624-628. doi: 10.1053/j. jvca.2009.08.003.

14. du Toit EF, Genis A, Opie LH, 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. doi: 10.1038/bjp.2008.52.

15. Галагудза ММ. Оглушенный (станнированный) миокард: механизмы и клиническая значимость. Бюллетень ФЦСКЭ им. В. А. Алмазова. 2011;2:5-11.

16. Marban E. Patogenetic role for calcium in stunning? Cardiovasc Drugs Ther. 1991;5(5):891-893.

17. Sekili S, McCay PB, Li XY et al. Direct evidence that the hydroxyl radical plays a pathogenetic role in myocardial “stunning” in the conscious dog and demonstration that stunning can be markedly attenuated without subsequent adverse effect. Circ Res. 1993;73(4):705-723.

18. Papp Z, Édes I, Fruhwald S, De Hert SG et al. Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol. 2012;159(2):82-87. doi: 10.1016/j.ijcard.2011.07.022.

19. Papp Z, Csapó K, Pollesello P, Haikala H, Edes I. Pharmacological mechanisms contributing to the clinical efficacy of levosimendan. Cardiovasc Drug Rev. 2005;23(1):71-98.