毒毛旋花子苷给药引起心肌收缩—舒张过程中钠钙交换体的功能

引言。强心苷通过影响Na⁺–Ca²⁺交换而影响心肌收缩力，但该机制的独立作用仍了解不足。本研究旨在确定毒毛旋花子苷对仅由钠钙交换系统产生的心脏收缩的影响。

材料与方法。实验采用Langendorff技术，通过主动脉灌流分离的Wistar实验大鼠心脏进行。通过使用不同Na⁺浓度的溶液进行灌流来诱导收缩。将作为研究药物使用的安瓿装毒毛旋花子苷加入灌流液中，最终浓度最高达0.5 μmol/L。对照组给予等体积生理盐水。

结果。实验显示，在每一次Na⁺–Ca²⁺交换激活循环中，心脏均继续发生收缩和舒张。然而，第二次重复刺激时的收缩速率降低了32%。毒毛旋花子苷在三次重复刺激中均降低了收缩力。在第一次刺激期间观察到尤其显著的障碍，降低幅度为78%。肌肉收缩和舒张发生在舒张期肌张力逐渐升高的条件下。鉴于毒毛旋花子苷可降低Na⁺/K⁺-三磷酸腺苷酶（Na⁺/K⁺-ATPase）的活性，我们的实验清楚地证明了该强心苷具有增加细胞内钠浓度并继而增加钙浓度的能力。在存在毒毛旋花子苷的情况下，钙通过Na⁺–Ca²⁺交换从细胞内反复外排被证明是无效的。心脏持续处于钙超载状态，这反映为心脏舒张期应力增加。

结论。当心肌细胞发生钙离子超载时，受毒毛旋花子苷影响的最终生理效应可能是负性的，而不是正性的。

1. Gurevich MA, Gavrilin AA. Сердечные гликозиды в современной клинической практике. Almanac of Clinical Medicine. 2014;(35):101–105. doi: 10.18786/2072-0505-2014-35-101-105

2. Umarova FT, Khasanova MA, Berdieva HYa, et. al. Изучение ингибирования сердечными гликозидами строфантидинового ряда фермента Na,K-АТФазы и их положительно-инотропное действие. Universum: chemistry and biology. 2022;5(95):1–7. doi: 10.32743/UniChem.2022.95.5.13563

3. Altamirano J, Li X, DeSantiago J, et. al. The inotropic effect of cardioactive glycosides in ventricular myocytes requires Na+–Ca2+ exchanger function. J Physiol. 2006;575(3):845–854. doi: 10.1113/jphysiol.2006.111252

4. Terrar DA. Calcium signaling in the heart. Adv Exp Med Biol. 2020;1131:395–443. doi: 10.1007/978-3-030-12457-1_16

5. Сannell MB, Grantham CJ, Main MJ, et. al. The roles of the sodium and calcium current in triggering calcium release from the sarcoplasmic reticulum. Ann N Y Acad Sci. 1996;779:443–450. doi: 10.1111/j.1749-6632.1996.tb44819

6. Aronsen JM, Swift F, Sejersted OM. Cardiac sodium transport and excitation– contraction coupling.J Mol Cell Cardiol. 2013;61:11–19. doi: 10.1016/j.yjmcc.2013.06.003

7. Weber CR, Piacentino V 3rd, Ginsburg KS, et. al. Na+–Ca2+ exchange current and submembrane [Ca2+] during the cardiac action potential. Circ Res. 2002;90(2):182– 189. doi: 10.1161/hh0202.103940

8. Berezhnova TA, Moshurov IP, Baofeng Ya, et. al. Effect of cyclophosphamide on regulation of heart contractions by means of sodium calcium exchanger. Res. Results Pharmacol. 2025;11(1):1–12. doi: 10.18413/rrpharmacology.11.539

9. Lee HI, Lee BK, Jeong KW, et. al. Potassium-induced cardiac arrest during conventional cardiopulmonary resuscitation in a porcine model of prolonged ventricular fibrillation cardiac arrest: a feasibility study. Resuscitation. 2013;84(3):378– 383. doi: 10.1016/j.resuscitation.2012.08.324

10. Lehnart SE, Maier LS, Hasenfuss G. Abnormalities of calcium metabolism and myocardial contractility depression in the failing heart. Heart Fail Rev. 2009;14(4):213– 224. doi: 10.1007/s10741-009-9146-x

11. Nagy N, Toth N, Nanasi PP. Antiarrhythmic and inotropic effects of selective Na+/ Ca2+ exchanger inhibition: what can we learn from the pharmacological studies? Int J Mol Sci. 2022;23(23):14651. doi: 10.3390/ijms232314651

12. Kuptsova AM, Bugrov RK, Ziyatdinova NI, et. al. Острейшая стадия инфаркта миокарда: влияние блокады If на изолированное сердце крыс. Ulyanovsk Journal of Medical and Biological Sciences. 2022;3:106–119. doi: 10.34014/2227-1848-2022-3-106-119

13. Metelitsa VI. Справочник по клинической фармакологии сердечно-сосудистых лекарственных средств, 3-е издание. Moscow: Medical Information Agency; 2005. 1528 p. ISBN 5-89481-320-4

14. Konstantinou DМ, Karvounis H, Giannakoulas G. Digoxin in heart failure with a reduced ejection fraction: a risk factor or a risk marker. Cardiology. 2016;134(3):311– 319. doi: 10.1159/000444078

15. Echteld CJ, Kirkels JH, Eijgelshoven MH, et. al. Intracellular sodium during ischemia and calcium-free perfusion: a 23Na NMR study. J Mol Cell Cardiol. 1991;23(3):297–307. doi: 10.1016/0022-2828(91)90066-u

16. Hamilto Sh, Veress R, Belevych A, et. al. The role of calcium homeostasis remodeling in inherited cardiac arrhythmia syndromes. Pflugers Arch. 2021;473:377–387. doi: 10.1007/s00424-020-02505-y17.

17. Giladi M, Bohbot H, Buki T, et. al. Dynamic features of allosteric Ca2+ sensor in tissue-specific NCX variants. Cell Calcium. 2012;51(6):478–485. doi: 10.1016/j.ceca.2012.04.00718.

18. Toda N. Effects of calcium, sodium and potassium ions on contractility of isolated atria and their responses to noradrenaline. Br J Pharmacol. 1969;36(2):350–367. doi: 10.1111/j.1476-5381.1969.tb09510.x.