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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. 2002; 48(6): 3-10


Protection of heart from reperfusion injury andineffective oxygen using by inhibitors of the mitochondrial permeability transition pore

Sagach V.F., Shymanskaya T.V., Nadtochiy S.M.

    A.A. Bogomoletz Institute of Physiology NAS Ukraine, Kiev


Abstract

In experiments on isolated hearts of guinea-pig, perfused under Langendorff preparation, possible protection of hearts from reperfusion injury by the known inhibitors of mitochondrial permeability transition pore - cyclosporin A, and trolox - water-soluble vitamin E was studied. It has been shown that cardiac reperfusion was followed with an increase in an oxygen cost of myocardial work (by 83% from control level in 40 min of reperfusion), in addition to the disturbances of cardiac contractility, tone of the coronary vessels and heart rate. The heart function and myocardial oxygen metabolism disturbances, due to global 20 min ischaemia and reperfusion, were essentially decreased by a preliminary application of investigated agents. Trolox improved cardiac recovery both when it was perfused in vitro and after its administration per os. In 40 min of heart reperfusion LVdeveloped pressure was 79% as compared to 51% in that at control; dР/dtmax and dР/dtmin were 88% and 85% accordingly against 66% and 45% in control; oxygen cost of myocardial work didn“t change reliably). Conclusion: postreperfusion disturbances of cardiac contractility, tone of the coronary vessels and heart rate, as well as noneffective oxygen utilization by the heart tissue were due to an opening of mitochondrial permeability transition pore.

References

  1. Сагач В.Ф., Шиманська Т.В., Надточій С.М. Вивчення ролі оксиду азоту у змінах споживання кисню та кисневої вартості роботи серцевого м’яза // Фізіол. журн. –2000. – 46, №2. – С.33 – 40.
  2. Ткаченко М.М., Сагач В.Ф., Коцюруба А.В. та ін. Ендотелійзалежні скорочувальні реакції судинних гладеньких м’язів і вміст вільних радикалів кисню у щурів за умов старіння // Фізіол. журн. –2002. – 48, №4. – С.3 – 13.
  3. Brookes P.S., Salinas E.P., Usmar K.D. et al. Concentration-dependent effects of nitric oxise on mitochondrial permeability transition and cytochrome C release // J.Biol.Chemistry .– 2000. – 275, N 27. –P. 20474 – 20478.
  4. Crompton M., Costi A. A heart mitochondrial Ca induced pore of possible relevance to reperfusion injury // Biochem.J. – 1990. – 266. – P.33 – 39.
  5. Crompton M., Andreeva L. On the involment of a mitochondrial pore in reperfusion injury // Bas. Res. Cardiol. – 1993. – 88. – P.513 – 523.
  6. Crompton M. The mitochondrial permeability transition pore and its role in cell death // Biochem.J. – 1999. – 341. – P.233 – 249.
  7. Crompton M . Mitichondrial intermembrane junctional complexes and their role in cell death// J. Physiol. – 2000. – 529, N1. – P.11 – 21.
  8. Chen Y., Traverse J.H., Du R. et al. Nitric oxide modulates myocardial oxygen consumption in failing heart// Circulation.– 2002.– 106, N2.– P.273 – 279.
  9. 9. Duchen M. Mitochondrial and calcium: from cell signalling to cell death // J.Physiol. – 2000. – 529, N1. – P.57 – 68.
  10. 10. Griffiths E., Halestrap A. Protection by cyclosporin A of ischaemia/reperfusion induced damage in isolated heart // J.Mol.Cell.Cardiol. – 1993. – 25. – P.1461–1469.
  11. Griffiths E., Halestrap A. Mitichondrial non specific pores remain closed during cardiac ischaemia but open upon reperfusion // Biochem.J. – 1995. – 307. – P.93 – 98.
  12. Halestrap A. Mitochondria and cell death // The Biochemist. – 2000. – P.19 – 24.
  13. Hunter P., Haworth R. The Ca induced membrane transition in mitochondria // Arch. And Biochem.Biophys. –1979.– 195. – P.468 – 477.
  14. Korge P., Goldhaber J., Weiss J. Phenilarsine oxide induces mitochondrial permeability transition, hypercontracture, and cardiac cell death // Amer. J.Physiol. –2001. – 280. –P.H2203 – H2213.
  15. Mather M., Rottenberg H. Aging enhances the activation of permeability transition pore in mitochondria // Biochem. and Biophys.Res.Com. – 2000. – 273. – P.603 – 608.
  16. Nazareth W., Yafei N., Crompton M. Ingibition of anoxiainduced injury in heart myocytes by cyclosporin A //J.Mol.Cell.Cardiol. – 1991. – 23. – P.1351 – 1354.
  17. Neely J.R., Liebermeister H., Battersby E.J. et al. Effect of pressure development on oxygen consumption by isolated heart // Amer. J. Physiol.– 1967. – 221. – P.804 – 813.
  18. Paxinou E., Weisse M., Chen O. et al. Dynamic regulation of metabolism and respiration by endogenously produced nitric oxide protects against oxidative stress// Proc. Natl. Acad. Sci USA. – 2001. – 98, N20. –P.11575 – 11580.
  19. 19. Sagach V., Scrosati M., Fielding J. et al. The watersoluble vitamin E analogue trolox protects against ischaemia/reperfusion damage in vitro and ex vivo. A comparison with vitamin E // Pharmacol.Res. – 2002. –45. – P.435 – 439.
  20. 20. Shen W., Xu X., Ochoa M. et al. Role of nitric oxide in the regulation of oxygen consumption in conscious dogs //Circulat. Res. – 1994. – 75, N 6. – P.1086 – 1095.
  21. Zorov D.B., Filburn C.R., Klotz L-O. et al. Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes // J. Exp.Med. – 2000. – 192, N7. – P.1001 – 1014.

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