Українська Русский English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2011; 57(1): 55-65


Effect of medical form of flocalin on the course of myocardial reperfusion injury

Strutyns'kyĭ RB, Rovenets' RA, Neshcheret OP, Tumanovs'ka LV, Boĭchuk TM, Dzhuran BV, Moĭbenko OO

    Bogomoletz Institute of physiology NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz57.01.055

Abstract

In experiments on anaesthetized dogs with modeling of experi­mental ischemia (90min) and reperfusion (180min), the car­dioprotective influence of the pharmacological precondition­ing caused by intragastric (with a help of catheter) introduc­tion of medicinal form (tablets) of new fluorine-containing opener of ATP-sensitive potassium channels flocalin was shown. Flocalin was introduced in a dose 2,2mg/kg, which in the conditions of physiological norm has a minimum influence on the parameters of cardiohemodynamic. The conducted research allowed to define the changes of these parameters during development of antiischemic protective effect of phar­macological preconditioning, caused by the medicinal form of flocalin, and describes basic cardioprotective mechanisms, related to the changes of cardiohemodynamic in the dynamics of ischemia-reperfusion of myocardium. In our opinion, to positive influences of flocalin, which are possibly related to cardioprotective action, it is possible to add the prevention of an increase of general peripheral resistance, resistance of coronal vessels of heart, and relative preservation of myocardium contractility in the period of reperfusion. Also these positive effects can be explained by moderate decrease of blood pres­sure that decreases the loading on the damaged heart and al­lows to preserve cardiac emission in the first period of is­chemia. One of the major indexes of development of protec­tive mechanism of pharmacological preconditioning caused by preischemic introduction of medicinal form of flocalin is the diminishing of infarct size of myocardium in experiments with ischemia-reperfusion of myocardium on 42,53% ± 2,91% ver­sus control experiments.

Keywords: KATP channels, floсalin, medicinal form, ischemia-reperfusion, сardiohemodynamic, infarct of myocardium

References

  1. Moibenko OO, Strutinsky RB, Yagupolsky LM, Mohort MA Development and preparation for the introduction of a new domestic cardioprotector drug fluorine-containing activator of ATP-dependent potassium channels Flokalin . Science and Innovation. 2006. 2, N 4. p. 114-119. CrossRef  
  2. Moibenko OO, Strutinsky RB, Yagupolsky LM, Mohort MA, Shalamay AS Organization of factory production of the drug Flokalin a new domestic myotropic antispasmodic and cardioprotector . Science and Innovation.  - 2009. 5, N 1. P.80-84. CrossRef  
  3. Morozov MA Emergency medical care. Tutorial. allowance. SPb: Didactics, 1995. 215 p.
  4.  
  5. Strutinsky RB Investigation of the influence of new activators of ATP-dependent potassium channels on cardiac function and vasomotor responses in normal and pathological conditions. Author's abstract. diss. ... biol. Sciences. 2002. 20 p.
  6.  
  7. Strutyns'kyĭ RB, Neshcheret OP, Tumanovs'ka LV, Rovenets' RA, Moĭbenko OO. [Cardioprotective effects of flokalin in experiments in vivo: influence on hemodynamic and myocardial lesions in ischemia-reperfusion].. Fiziol Zh. 2009;55(5) P.9-16.
  8.  
  9. Strutyns'kyĭ RB, Moĭbenko OO, Iahupol's'kyĭ LM, Iuz'kiv MIa, Kvochina LI, Shysh AM. Cardioprotective effects of a new fluorine-containing synthetic activator of ATP-dependent potassium channels.. Fiziol Zh. 2001. 47, N 2. P.16-23.
  10.  
  11. Strutinsky P., Mohort M., Yagupolsky L., Moybenko O. Flokalin a new domestic cardioprotector . Visn. pharmacology and pharmacy. 2010. N 3. P.44-56.
  12.  
  13. Strutinsky RB, Pivovar SN,. Moibenko AA ATP-dependent potassium channels and their role as a central link of cardioprotection in ischemia myocardial reperfusion. In book: Endogenous mechanisms of cardioprotection as a basis of pathogenetic therapy of heart diseases . Ed. A.A. Moibenko, V.E. Dosenko, AN Parkhomenko. K .: Sciences. opinion, 2008. p. 206-252.
  14.  
  15. Strutyns'kyĭ RB, Pyvovar SM, Tumanovs'ka LV, Moĭbenko OO. Cardioprotective effects of flokalin: relative role of activation of sarcolemmal and mitochondrial adenosine triphosphate-dependent potassium channels. . Fiziol Zh.  - 2008. 54, N 6. p. 15-23.
  16.  
  17. Strutyns'kyĭ RB, Rovenets' RA, Neshcheret OP. [Effect of a new activator of adenosine triphosphate-sensitive potassium channels flocalin on the glucose level in blood].. Fiziol Zh. 2010. 56, N 6. p. 39-47. CrossRef PubMed
  18.  
  19. Strutinskiy RB, Frantsuzova SB., Rovenets RA, Tumanovskaya LV, Moybenko OO Flokalin a new domestic cardioprotector . V National Congress of Pathophysiologists of Ukraine with International Participation "Modern Problems of Pathophysiology: From Molecular-Genetic to Integrative Aspects", September 17-19, 2008, Zaporizhzhya . Pathology. 2008. 5, N 3. p. 22.
  20.  
  21. Klebanov BM, IIMaletina, LM Yagupolsky and others. Stalemate. 17071A Ukraine, IPC6 A 61 K 31. 03. N-(1,2,2-trimethylpropyl) N '' cyano-N'-arylguanidines with fluorine-containing substituents in the aromatic nucleus exhibiting hypotensive and cardiotonic action No. 95041977; Statement 04. 26. 95; Publ. 10. 31. 97 Industrial property. 1997. N 5. p. 3.1.76.
  22.  
  23. Alekseev A.E., Hodgson D.M., Karger A.B., Park S., Zingman L.V., Terzic F. 2005 ATP-sensitive K+ channel channel. enzyme multimer: Metabolic gating in the heart . J. Molec. and Cell Cardiol . 2005. 38. P.895-905. CrossRef PubMed PubMedCentral
  24.  
  25. Bhatnagar A., Bolli R. Modulation of K channels to protect the ischemic myocardium: Clinical implications . Exp. Clin. Cardiol . 1999. 4, N 1. P.20-22.
  26.  
  27. Costa A.D., Quinlan C.L., Andrukhiv A., West I.C, Jaburek M., Garlid K.D. The direct physiological ef­fects of mitoK(ATP) opening on heart mitochondria . Amer. J. Physiol. Heart. Circulat. Physiol. 2006. 290(1). P.406-415. CrossRef PubMed
  28.  
  29. Dzeja P.P., Bast P., Ozcan C, Valverde A., Holmuha-medov E.L., Wylen D.G.L.V., Terzic A. Targeting nucle-otide-requiring enzymes: implications for diazoxide-induced cardioprotection . Ibid. 2003. 284, N 4. P. 1048-1056. CrossRef PubMed
  30.  
  31. Garlid KD and Paucek P. Mitochondrial potassium transport: the K O'Rourke cycle . Biochim. and Biophys. Acta. 2003. 1606. P. 23-41. CrossRef  
  32. Gross G.J., Fryer R.M. Sarcolemmal versus mitochon­drial ATP-sensitive K+ channels and myocardial pre­conditioning . Circulat. Res. 1999. 84, N 9. P.973-979. CrossRef PubMed
  33.  
  34. Hanley PJ, Daut J. K(ATP) channels and precondi­tioning: a re-examination of the role of mitochondrial K(ATP) channels and an overview of alternative mecha­nisms . J. Mol. Cell. Cardiol. 2005. 1. P.17-50. CrossRef PubMed
  35.  
  36. Holmuhamedov E.L., Jovanovic S., Dzeja P.P., Jovanovic A., Terzic A. Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function . Amer. J. Physiol. Heart. Circulat.. Physiol. 1998. 275. P. 1567-1576. CrossRef PubMed
  37.  
  38. Jahandir A., Terzic A. K channel therapeutics at the bedside . J. Mol. and Cellular Cardiol. 2005. 39. P. 99-112. CrossRef PubMed PubMedCentral
  39.  
  40. O'Rourke B. Myocardial K channels in precondi­tioning . Circulat. Res. 2000. 87. P. 845-855. CrossRef PubMed
  41.  
  42. Teshima Y, Akao M., Li R.A., Chong T.H., Baumgartner W.A., Johnston M.V., Marban E. Mitochondrial ATP-sensitive potassium channel activation protects cerebel­lar granule neurons from apoptosis induced by oxidative stress . Stroke. 2003. 34, N 7. P. 1796-802. CrossRef PubMed
  43.  
  44. Wakahara N., Katoh H, Yaguchi Y, Uehara A, Satoh H, Terada H, Fujise Y, Hayashi H, Difference in the car-dioprotective mechanisms between Ischemic pre­conditioning and pharmacological preconditioning by diazoxide in rat hearts . Circulat. J. 2004. 68. P.156-162. CrossRef PubMed
  45.  
  46. Yagupolskii L.M., Maletina I.I., Klebanov B.M. Fluo­rine-containing cardiovascular drugs R. Filler et al. Organofluorine compounds in medicinal chemistry and biomedical applications. Amsterdam-London- New York-Tokyo: Elesevier Science Publishers B.V., 1993. P. 73-99.
  47.  
  48. Yagupolskii L.M., Maletina I.I., Petko K.I.. New fluo­rine-containing hypotensive preparations (Rev.) . J. Fluor. Chem. 2001. 109. P. 87-94. CrossRef  
  49. Yao Z., Cavero I., Gross G. J. Activation of cardiac K channels: an endogenous protective mechanism during repetitive ischemia . Amer. J. Physiol. 264. (Heart. Circulat. Physiol. 33). 1993, N 2. P.H495-H504. CrossRef PubMed

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2019.