ANTIISCHEMIC AND ANTIARRHYTHMIC EFFICIENCY OF REMOTE ISCHEMIC POST-CONDITIONING DURING ISCHEMIA-REPERFUSION IN RATS WITH HYPERCHOLESTEROLEMIA

The search for new effective methods of preventing or reducing ischemic myocardial injury is an actual problem of modern experimental and clinical medicine. In clinical practice, the need to protect the myocardium from ischemic and reperfusion injury most often occurs in patients with various risk factors for cardiovascular diseases, including hypercholesterolemia. The aim of the study was to determine the reproducibility of antiischemic and antiarrhythmic effects of the remote ischemic post-conditioning myocardium of rats with hypercholesterolemia. It was found that the remote ischemic post-conditioning is not effective in terms of necrosis area size limits in the left ventricle during ischemia-reperfusion in rats with hypercholesterolemia. The remote ischemic post-conditioning is effective in reducing the duration of cardiac arrhythmias during acute myocardial ischemia-reperfusion injury in rats with hypercholesterolemia. The duration of ischemic heart rhythm disturbances decreased by 85 % (p < 0.05). The results of the performed study are of great importance for practical medicine. The findings indicate the need for a differentiated approach to the appointment of the remote ischemic post-conditioning in patients with acute myocardial infarction. The existence of such a risk factor for cardiovascular diseases such as hypercholesterolemia can be a criterion for exclusion of the remote ischemic post-conditioning as a way of reducing ischemic and reperfusion injury of the myocardium in patients with acute myocardial infarction.

antiischemic effect, antiarrhythmic effect, remote ischemic post-conditioning, hypercholesterolemia, risk area, necrosis area

1. Mrochek A. G., Grakovich A. A., Kozlov I. D., Gorbachev V. V. Cardiovascular diseases in the Republic of Belarus: the analysis of the situation and control strategy. Minsk, Belaruskaja navuka [Belarusian science], 2011, 341 p. (in Russian).

2. Shliakhto E. V., Nifontov E. M., Galagurda M. M. Limitation of ischemic and reperfusion injury of the myocardium using pre- and postconditioning: molecular mechanisms and targets for pharmacotherapy. Kreativnaia kardiologiia [Creative Cardiology], 2007, no. 1/2, pp. 75–101. (in Russian).

3. Cokkinos D. V., Pantos C. Myocardial protection in man – From research concept to clinical practice. Heart Failure Reviews, 2007, vol. 12, no. 3/4, pp. 345–362. doi: 10.1007/s10741-007-9030-5.

4. Haunsenloy D. J., Yellon D. M. Preconditioning and postconditioning: united at reperfusion. Pharmacology & Therapeutics, 2007, vol. 116, no. 2, pp. 173–191. doi.org/10.1016/j.pharmthera.2007.06.005.

5. Basalay М., Barsukevich V., Mastitskaya S., Mrochek A., Pernow J., Sjöquist P. O., Ackland G. L., Gourine A. V., Gourine A. Remote ischaemic pre- and delayed postconditioning – similar degree of cardioprotection but distinct mechanisms. Journal of Experimental Physiology, 2012, vol. 97, no. 8, pp. 908–917. doi: 10.1113/expphysiol.2012.064923.

6. Schmidt M. R., Kristiansen S. B., Botker H. E. Remote ischemic preconditioning: no loss in clinical translation. Circulation Research, 2013, vol. 113, no. 12, pp. 1278–1280. doi: 10.1161/CIRCRESAHA.113.302942.

7. Osipov R. M., Bianchi C., Feng J., Clements R. T., Liu Yu., Robich M. P., Glazer H. P., Sodha N. R., Sellke F. W. Effect of hypercholesterolemia on myocardial necrosis and apoptosis in the setting of ischemia-reperfusion. Circulation, 2009, vol. 120, no. 11, pp. 22–30. doi: 10.1161/CIRCULATIONAHA.108.842724.

8. Szilvassy Z., Ferdinandy P., Szilvassy Ju., Nagy I., Karcsu S., Lonovics J., Dux L., Koltai M. The loss of pacing- induced preconditioning in atherosclerotic rabbits: role of hypercholesterolemia. Journal of Molecular and Cellular Cardiology, 1995, vol. 27, no. 12, pp. 2559–2569. doi: http://dx.doi.org/10.1006/jmcc.1995.0043.

9. Krisztina K., Csonka C., Bencsik P., Fodor G., Ferdinandy P. The cardioprotective effect of postconditioning is lost in cholesterol diet-induced hyperlipidemia in rats. Journal of Molecular and Cellular Cardiology, 2006, vol. 40, no. 6, pp. 976–977. doi: http://dx.doi.org/10.1016/j.yjmcc.2006.03.168.

10. Wu N., Zhang X., Guan Y., Shu W., Jia P., Jia D. Hypercholesterolemia fibrogates the cardioprotection of ischemic postconditioning in isolated rat heart: roles of glycogen synthase kinase-3β and the mitochondrial permeability transition pore. Cell Biochemistry and Biophysics, 2014, vol. 69, no. 1, pp. 123–130. doi:10.1007/s12013-013-9778-2.

11. D’Annunzio V., Donato M., Buchholz B., Pérez V., Miksztowicz V., Berg G., Gelpi R. J. High cholesterol diet effects on ischemia-reperfusion injury of the heart. Canadian Journal of Physiology and Pharmacology, 2012, vol. 90, no. 9, pp. 1185–1196. doi: 10.1139/y2012-085.

12. Kremastinos D. T., Bofilis E., Karavolias G. K., Papalois A., Kaklamanis L., Iliodromitis E. K. Preconditioning limits myocardial infarct size in hypercholesterolemic rabbit. Atherosclerosis, 2000, vol. 150, no. 1, pp. 81–89.

13. Iliodromitis E. K., Zoga A., Vrettou A., Andreadou I., Paraskevaidis I. A., Kaklamanis L., Kremastinos D. T.

14. The effectiveness of postconditioning and preconditioning on infarct size in hypercholesterolemic and normal anesthetized rabbits. Atherosclerosis, 2006, vol. 188, no. 2, pp. 356–362. doi: http://dx.doi.org/10.1016/j.atherosclerosis.2005.11.023.

15. Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. Available at: http:// www.eur-lex.europa.eu. (Accessed 21 May 2012).

16. Good Laboratory Practice (GLP), TСP 125-2008 (02040), Technical Code of Good Practice. Minsk, Ministerstvo zdravoohranenija Respubliki Belarus’ [Ministry of Health of the Republic of Belarus], 2008. 35 p. (in Russian).

17. The animal health rules for the reception, care and dissection of the experimental animals in the vivarium research institutes, stations, laboratories, schools and nurseries, VSP, May 21, 2010, no. 36. The National Fund of Technical Legal Acts of the Republic of Belarus. Avialable at: http:// www.tnpa.by (Accessed 11 May 2012). (in Russian).

18. On the norms of feeding laboratory animals and producers, Order of Health of the USSR M-va, 10 March 1966, no. 163. Complete Collection of legislation of the USSR. Avialable at: http://www.ussrdoc.com. (Accessed 01 April 2012). (in Russian).

19. Clark C. Coronary artery ligation in anesthetized rats as a method for the production of experimental dysrhythmias and for the determination of infarct size. Journal of Pharmacological Methods, 1980, vol. 3, no. 4, pp. 357–368. (in Russian).

20. Fishbein M. C. Early phase acute myocardial infarct size quantification: validation of the triphenyl tetrazolium chloride tissue enzyme staining technique. American Heart Journal, 1981, vol. 101, no. 5, pp. 593–600.

21. Jung O., Jung W., Malinski T., Wiemer G., Schoelkens B. A., Linz W. Ischemic preconditioning and infarct mass: the effect of hypercholesterolemia and endothelial dysfunction. Clinical and Experimental Hypertension, 2000, vol. 22, no. 2, pp. 165–179.

22. Sack M., Murphy E. The role of co-morbidities in cardioprotection. Journal of Cardiovascular Pharmacology and Therapeutics, 2011, vol. 16, no. 3/4, pp. 267–272.

23. Samoylov M. O., Rybnikova E. A., Churilova A. V. Signal molecular and hormonal mechanisms of formation of the hypoxic preconditioning protective effects. Patologicheskaia fiziologiia i eksperimental’naia terapiia [Pathological Physiology and Experimental Therapy], 2012, no. 3. pp. 3–10. (in Russian).