vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"vestim-366Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEПРОТИВОИШЕМИЧЕСКАЯ И АНТИАРИТМИЧЕСКАЯ ЭФФЕКТИВНОСТЬ ДИСТАНТНОГО ИШЕМИЧЕСКОГО ПОСТКОНДИЦИОНИРОВАНИЯ ПРИ ИШЕМИИ-РЕПЕРФУЗИИ МИОКАРДА У КРЫС С ГИПЕРХОЛЕСТЕРОЛЕМИЕЙANTIISCHEMIC AND ANTIARRHYTHMIC EFFICIENCY OF REMOTE ISCHEMIC POST-CONDITIONING DURING ISCHEMIA-REPERFUSION IN RATS WITH HYPERCHOLESTEROLEMIAВисмонтФ. И.VismontF. I.

чл.-кор. НАН Беларуси, д-р мед. наук, профессор, заведующий кафедрой

Corresponding Member, D. Sc. (Med.), Professor, Head of the Department

patfiz@bsmu.byЧепелевС. Н.ChepelevS. N.

ассистент кафедры

Assistant of the Department

patfiz@bsmu.byЮшкевичП. Ф.JushkevichP. F.

канд. мед. наук, ассистент кафедры

Ph. D. (Med.), assistant of the Department

patfiz@bsmu.byБелорусский государственный медицинский университетBelarusian State Medical University201708082017021625Copyright © Висмонт Ф.И., Чепелев С.Н., Юшкевич П.Ф., 20172017Висмонт Ф.И., Чепелев С.Н., Юшкевич П.Ф.Vismont F.I., Chepelev S.N., Jushkevich P.F.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/366

Поиск новых эффективных методов предотвращения или ослабления ишемического повреждения миокарда является актуальной задачей современной экспериментальной и клинической медицины. В клинической практике необходимость защиты миокарда от ишемического и реперфузионного повреждения чаще всего возникает у пациентов с различными факторами риска сердечно-сосудистых заболеваний, к числу которых относится и гиперхолестеролемия. Целью исследования было выявление воспроизводимости противоишемического и антиаритмического эффектов дистантного ишемического посткондиционирования (ДИПостК) миокарда у крыс с гиперхолестеролемией. Установлено, что ДИПостК при ишемии-реперфузии миокарда у крыс с гиперхолестеролемией не эффективно в плане ограничения размеров зоны некроза в миокарде левого желудочка и эффективно в плане снижения продолжительности нарушений сердечного ритма. Длительность ишемических нарушений сердечного ритма уменьшалась на 85 % (p < 0,05). Результаты исследования имеют важное значение для практической медицины. Полученные данные свидетельствуют о необходимости дифференцированного подхода к назначению ДИПостК пациентам с острым инфарктом миокарда. Наличие такого фактора риска сердечно-сосудистых заболеваний, как гиперхолестеролемия, может служить критерием для исключения ДИПостК с целью снижения ишемических и реперфузионных повреждений миокарда у таких пациентов. 

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.

противоишемический эффектантиаритмический эффектдистантное ишемическое посткондиционированиегиперхолестеролемиязона рисказона некрозаantiischemic effectantiarrhythmic effectremote ischemic post-conditioninghypercholesterolemiarisk areanecrosis areaReferencesСердечно-сосудистые заболевания в Республике Беларусь: анализ ситуации и стратегии контроля / А. Г. Мрочек [и др.] ; Нац. акад. наук Беларуси, Отд-ние мед. наук, Респ. науч.-практ. центр «Кардиология». – Минск : Беларус. на-вука, 2011. – 341 с.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).Шляхто, Е. В. Ограничение ишемического и реперфузионного повреждения миокарда с помощью пре- и пост-кондиционирования: молекулярные механизмы и мишени для фармакотерапии / Е. В. Шляхто, Е. М. Нифонтов, М. М. Галагурда // Креатив. кардиология. – 2007. – № 1/2. – С. 75–101.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).Cokkinos, D. V. Myocardial protection in man – From research concept to clinical practice / D. V. Cokkinos, C. Pantos // Heart Fail. Rev. – 2007. – Vol. 12, N 3/4. – P. 345–362.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.Hausenloy, D. J. Preconditioning and postconditioning: united at reperfusion / D. J. Haunsenloy, D. M. Yellon // Pharmacol Ther. – 2007. – Vol. 116, iss. 2. – P. 173–191.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.Remote ischaemic pre- and delayed postconditioning – similar degree of cardioprotection but distinct mechanisms / М. Basalay [et. al.] // J. Exp. Physiol. – 2012. – Vol. 97, N 8. – P. 908–917.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.Schmidt, M. R. Remote ischemic preconditioning: no loss in clinical translation / M. R. Schmidt, S. B. Kristiansen, H. E. Botker // Circ. Res. – 2013. – Vol. 113, N 12. – P. 1278–1280.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.Effect of hypercholesterolemia on myocardial necrosis and apoptosis in the setting of ischemia-reperfusion / R. M. Osipov [et al.] // Circulation. – 2009. – Vol. 120, suppl. 11. – P. 22–30.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.The loss of pacing-induced preconditioning in atherosclerotic rabbits: role of hypercholesterolemia / Z. Szilvassy [et al.] // J. Mol. Cell. Cardiol. – 1995. – Vol. 27, iss. 12. – P. 2559–2569.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.The cardioprotective effect of postconditioning is lost in cholesterol diet-induced hyperlipidemia in rats / K. Krisztina [et al.] // J. Mol. Cell. Cardiol. – 2006. – Vol. 40, iss. 6. – P. 976–977.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.Hypercholesterolemia fibrogates the cardioprotection of ischemic postconditioning in isolated rat heart: roles of glycogen synthase kinase-3β and the mitochondrial permeability transition pore / N. Wu [et al.] // Cell. Biochem. Biophys. – 2014. – Vol. 69, iss. 1. – P. 123–130.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.High cholesterol diet effects on ischemia-reperfusion injury of the heart / V. D’Annunzio [et al.] // Can. J. Physiol. Pharmacol. – 2012. – Vol. 90, iss. 9. – P. 1185–1196.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.Preconditioning limits myocardial infarct size in hypercholesterolemic rabbits / D. T. Kremastinos [et al.] // Atherosclerosis. – 2000. – Vol. 150, iss. 1. – P. 81–89.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.The effectiveness of postconditioning and preconditioning on infarct size in hypercholesterolemic and normal anesthetized rabbits / E. K. Iliodromitis [et al.] // Atherosclerosis. – 2006. – Vol. 188, iss. 2. – P. 356–362.Iliodromitis E. K., Zoga A., Vrettou A., Andreadou I., Paraskevaidis I. A., Kaklamanis L., Kremastinos D. T.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 [Electronic resource]. – Mode of access: www.eur-lex.europa.eu. – Date of access: 21.05.2012.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.Надлежащая лабораторная практика = Належная лабараторная практыка = Good Laboratory Practice (GLP) : ТКП 125-2008 (02040). – Введ. 01.05.2008. – Минск : М-во здравоохранения Респ. Беларусь, 2008. – 35 с. – (Технический кодекс установившейся практики).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).Ветеринарно-санитарные правила по приему, уходу и вскрытию подопытных животных в вивариях научно-исследовательских институтов, станциях, лабораториях, учебных заведениях, а также в питомниках [Электронный ресурс] : ВСП, 21 мая 2010 г., № 36 // Национальный фонд технических нормативных правовых актов Республики Беларусь. – Режим доступа: www.tnpa.by. – Дата доступа: 11.05.2012.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).О нормах кормления лабораторных животных и продуцентов [Электронный ресурс] : приказ М-ва здравоохранения СССР, 10 марта 1966 г., № 163 // Полное собрание законодательства СССР. – Режим доступа: www.ussrdoc.com. – Дата доступа: 01.04.2012.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).Clark, C. Coronary artery ligation in anesthetized rats as a method for the production of experimental dysrhythmias and for the determination of infarct size / C. Clark // J. Pharmacol. Methods. – 1980. – Vol. 3, N 4. – P. 357–368.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).Fishbein, M. C. Early phase acute myocardial infarct size quantification: validation of the triphenyl tetrazolium chloride tissue enzyme staining technique / M. C. Fishbein // Am. Heart J. – 1981. – Vol. 101, N 5. – P. 593–600.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).Ischemic preconditioning and infarct mass: the effect of hypercholesterolemia and endothelial dysfunction / O. Jung [et al.] // Clin. Exp. Hypertens. – 2000. – Vol. 22, iss. 2. – P. 165–179.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.Sack, M. The role of co-morbidities in cardioprotection / M. Sack, E. Murphy // J. Cardiovasc. Pharmacol. Ther. – 2011. – Vol. 16, N 3/4. – P. 267–272.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.Самойлов, М. О. Сигнальные молекулярные и гормональные механизмы формирования протективных эффектов гипоксического прекондиционирования / М. О. Самойлов, Е. А. Рыбникова, А. В. Чурилова // Патолог. физиология и эксперим. терапия. – 2012, № 3. – С. 3–10.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.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).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).

The authors declare that there are no conflicts of interest present.