Anti-ischemic and antiarrhythmic activity of dibornol in conditions of multiple transitory myocardial ischemia in rats
https://doi.org/10.29001/2073-8552-2020-35-1-151-158
Abstract
Material and Methods. The experiment was performed on male Wistar rats with a model of myocardial ischemia caused by 5-time 3-minute occlusions of the left coronary artery, followed by 15-minute reperfusion periods. Rats of the experimental group received Dibornol 10 mg/kg intragastrically once for 4 days; control animals received an equivalent volume of 1% starch mucus. On the ECG, the magnitudes of the ST segment elevation were determined for minutes 1, 2, and 3 of each episode of ischemia and for minutes 5, 10, and 15 of reperfusion; the nature and duration of ventricular arrhythmias were determined as well.
Results. In the control group, the ST segment was elevated during all five episodes of ischemia. During reperfusion periods, a decrease in the elevation of the ST segment was detected, but no normalization occurred. Ischemic and reperfusionrelated ventricular arrhythmias were observed in the rats of the control group. Mortality in the control group reached 67% (6 animals out of 9). In the experimental group, in animals receiving Dibornol at a dose of 10 mg/kg, the occlusion of the left coronary artery was associated only with a slight elevation of the ST segment and its rapid recovery during reperfusion. Magnitudes of the ST segment elevation were significantly lower than the corresponding control values during all the episodes of ischemia. During reperfusion periods, the differences with the control group were more significant during the first to fourth periods and at minute 15 of the fifth reperfusion period. The death rate in the experimental group (1 animal out of 9) was significantly lower relative to the corresponding value in the control group.
Conclusion. The course preventive use of Dibornol in multiple myocardial ischemia/reperfusion had significant anti-ischemic and antiarrhythmic effects during reperfusion periods and significantly increased the survival rate in animal models.
About the Authors
G. A. ChernyshevaRussian Federation
Dr. Sci. (Med.), Leading Scientist
3, Lenin ave., Tomsk, 634050, Russian Federation
V. I. Smolyakova
Russian Federation
Ph.D., Scientist
3, Lenin ave., Tomsk, 634050, Russian Federation
T. M. Plotnikova
Russian Federation
Dr. Sci. (Med.), Professor, Department of Pharmacology
2, Moskovsky tract, Tomsk, 634050, Russian Federation
A. V. Kutchin
Russian Federation
Dr. Sci. (Chem.), Professor, Corresponding Member of the Russian Academy of Sciences, Head of Organic Chemistry Laboratory
48, Pervomaiskaya str., Komi Republic, Syktyvkar, 167000, Russian Federation
I. Yu. Chukicheva
Russian Federation
Dr. Sci. (Chem.), Senior Scientist
48, Pervomaiskaya str., Komi Republic, Syktyvkar, 167000, Russian Federation
M. B. Plotnikov
Russian Federation
Dr. Sci. (Med.), Professor, Head of Pharmacology Department
3, Lenin ave., Tomsk, 634050, Russian Federation
References
1. WHO. Cardiovascular disease. Newsletter No. 317, January 2015. http://www.who.int/ mediacentre/factsheets/fs317/ru/ (In Russ.).
2. Grebenchikov O.A., Likhvantsev V.V., Plotnikov E.Yu., Silachev D.N., Pevzner I.B., Zorova L.D. et al. Molecular mechanisms of ischemic-reperfusion syndrome and its therapy. Russian Journal of Anаеsthesiology and Reanimatology. 2014;3:59–67 (In Russ.).
3. Shlyakhto E.V., Nifontov E.M., Galagudza M.M. Limitation of ischemic and reperfusion myocardial damage by pre-and postconditioning: molecular mechanisms and targets for pharmacotherapy. Creative Cardiology. 2007;1–2:75–101 (In Russ.).
4. Chukicheva I.Yu., Kuchin A.V. Natural and synthetic terpenophenols. Russian Journal of General Chemistry. 2004;48(3):21–37 (In Russ.).
5. Plotnikov M.B., Chernysheva G.A., Smol’yakova V.I., Ivanov I.S., Kuchin A.V., Chukicheva I.Yu. et al. Neuroprotective effects and mechanisms of action of dibornol in cerebral ischemia. Annals of the Russian Аcademy of Мedical Sciences. 2009;11:12–17 (In Russ.).
6. Guidelines for pre-clinical trials of drugs; edit. A.N. Mironov. Part 1. Moscow: Grif and K; 2012:944 (In Russ.).
7. Wit A.L., Janse M.J. Reperfusion arrhythmias and sudden cardiac death: century of progress toward an understanding of the mechanisms. Circulation Research. 2001;89(9):741-743. DOI: 10.1161/hh2101.099661.
8. Aielo E., Jabr R., Cole W. Arrhythmia and delayed recovery of cardiac action potential during reperfusion after ischemia. Circulation Research. 1995;77(1):153–162. DOI: 10.1161/01.RES.77.1.153.
9. Collard C.D., Gelman S. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology. 2001;94(6):1133–1138. DOI: 10.1097/00000542-200106000-00030.
10. Bolli R., Triana J.F., Jeroudi M.O. Prolonged impairment of coronary vasodilatation after reversible ischemia. Evidence for microvascular “stunning”. Circulation Research. 1990;67(2):332–343. DOI: 10.1161/01.RES.67.2.332.
11. Carden D.L., Grange D.N. Pathophysiology of ischaemia-reperfusion injury. J. Pathology. 2000;19(3):255–266. DOI: 10.1002/(SICI)1096-9896(200002)190:3<255::AID-PATH526>3.0.CO;2-6.
12. Ambrosio G., Chiariello M. Myocardial reperfusion injury: mechanisms and management – overview. Am. J. Med. 1991;91(3С):86–88. DOI: 10.1016/0002-9343(91)90289-A.
13. Ito H., Maruyama A., Iwakura K., Takiuchi S., Masuyama T., Hori M. et al. Clinical implications of the ‘no reflow’ phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction. Circulation. 1996;93(2):223–228. DOI: 10.1161/01.CIR.93.2.223.
14. Pabla R., Buda A.J., Flynn D.M., Blessé S.A., Shin A.M., Curtis M.J. et al. Nitric oxide attenuates neutrophil-mediated myocardial contractile dysfunction after ischemia and reperfusion. Circulation Research. 1996;78:65–72. DOI: 10.1161/01.RES.78.1.65.
15. Bobrov V.A., Simorot V.N. Reperfusion arrhythmias: mechanisms of development, ways of correction. Therapeutic Аrchive. 1993;65(9):56–62 (In Russ.).
16. Vatutin N.T., Kalinkina N.V., Eshchenko Y.V., Kravchenko I.N. Reperfusion injury of the myocardium. Kardіohіrurgіya ta Intervencіjna Kardіologіya. 2013;1:15–22 (In Ukr.).
17. Kumar D., Jugdutt B. Apoptosis and oxidants in the heart. J. Lab. Clin. Med. 2003;142(5):288–297. DOI: 10.1016/S0022-2143(03)00148-3.
18. Bolli R. Oxygen-derived free radicals and myocardial reperfusion injury: an overview. Cardiovasc. Drugs Ther. 1991;5(2):249–268. DOI: 10.1007/BF00054747.
19. Smol’yakova V.I., Chernysheva G.A., Yanovskaya E.A., Gurto R.V., Kuchin A.V., Chukicheva I.Yu. et al. Distribution of 4-methyl-2,6-diisobornylphenol in rat tissues and organs. Experimental and Сlinical Рharmacology. 2014;77(9):28–31 (In Russ.). DOI: 10.30906/0869-2092-2014-77-9-28-31.
Review
For citations:
Chernysheva G.A., Smolyakova V.I., Plotnikova T.M., Kutchin A.V., Chukicheva I.Yu., Plotnikov M.B. Anti-ischemic and antiarrhythmic activity of dibornol in conditions of multiple transitory myocardial ischemia in rats. Siberian Journal of Clinical and Experimental Medicine. 2020;35(1):151-158. (In Russ.) https://doi.org/10.29001/2073-8552-2020-35-1-151-158