Shensong Yangxin capsules prevent ischemic arrhythmias by prolonging action potentials and alleviating Ca2+ overload

Zhao,Yixiu; Gao,Feng; Zhang,Yong; Wang,Hongtao; Zhu,Jiuxin; Chang,Liping; Du,Zhimin; Zhang,Yan

doi:10.3892/mmr.2016.5203

Shensong Yangxin capsules prevent ischemic arrhythmias by prolonging action potentials and alleviating Ca2+ overload

Authors:
- Yixiu Zhao
- Feng Gao
- Yong Zhang
- Hongtao Wang
- Jiuxin Zhu
- Liping Chang
- Zhimin Du
- Yan Zhang
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Affiliations: Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China, State Key Laboratory of Collateral Disease Research and Innovation Medicine, Hebei Yiling Pharmaceutical Research Institute, Shijiazhuang, Hebei 050000, P.R. China, Graduate School, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Clinical Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: April 28, 2016 https://doi.org/10.3892/mmr.2016.5203
Pages: 5185-5192

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Abstract

Shensong Yangxin capsules (SSYX) are an effective traditional Chinese medicine that has been used to treat coronary heart disease clinically. The present study aimed to establish whether SSYX prevent ischemic arrhythmias in rats, and to explore the underlying mechanisms. Male rats were pretreated with distilled water, SSYX and amiodarone for one week. Acute myocardial ischemia (AMI) was performed to induce ischemic arrhythmias. The incidence and severity of ischemic arrhythmias were evaluated. The action potential, transient outward K+ current (Ito) and inward rectifier K+ current (IK1) of rat cardiomyocytes were measured using the patch‑clamp technique. The intracellular Ca2+ concentration of the cardiomyocytes was measured using a laser scanning confocal microscope. The results revealed that SSYX lowered the incidence of arrhythmia markedly during AMI. Furthermore, SSYX delayed the appearance, and reduced the severity, of ischemic arrhythmias compared with the control. In addition, SSYX markedly decreased the ratio of the myocardial infarction region to the whole heart. In an in vitro study, SSYX prolonged the action potential duration of rat cardiomyocytes, and inhibited Ito and IK1 markedly. Additionally, SSYX inhibited Ca2+ elevation induced by KCl in cardiomyocytes. These results suggested that SSYX prevents ischemic arrhythmia, and the underlying mechanism responsible for this process may include prolonging the action potential and alleviating Ca2+ overload.

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1	Driessen HE, Bourgonje VJ, Van veen TA and Vos MA: New antiarrhythmic targets to control intracellular calcium handling. Neth Heart J. 22:198–213. 2014. View Article : Google Scholar : PubMed/NCBI
2	Gao FF, Hao SY, Huang ZQ, Zhang YM, Zhou YQ, Chen YC, Liu XP and Shi GG: Cardiac electrophysiological and antiarrhythmic effects of N-n-butyl haloperidol iodide. Cell Physiol Biochem. 25:433–442. 2010. View Article : Google Scholar : PubMed/NCBI
3	Davies MJ: Pathological view of sudden cardiac death. Br Heart J. 45:88–96. 1981. View Article : Google Scholar : PubMed/NCBI
4	Marbán E: Cardiac channelopathies. Nature. 415:213–218. 2002. View Article : Google Scholar : PubMed/NCBI
5	James RG, Arnold JM, Allen JD, Pantridge JF and Shanks RG: The effects of heart rate, myocardial ischemia and vagal stimulation on the threshold for ventricular fibrillation. Circulation. 55:311–317. 1977. View Article : Google Scholar : PubMed/NCBI
6	Fallavollita JA, Jacob S, Yong RF and Canty JM Jr: Regional alterations in SR Ca²⁺-ATPase, phospholamban and HSP-70 expression in chronic hibernating myocardium. Am J Physiol. 277:H1418–H1428. 1999.PubMed/NCBI
7	Prunier F, Kawase Y, Gianni D, Scapin C, Danik SB, Ellinor PT, Hajjar RJ and Del Monte F: Prevention of ventricular arrhythmias with sarcoplasmic reticulum Ca²⁺ ATPase pump overexpression in a porcine model of ischemia reperfusion. Circulation. 118:614–624. 2008. View Article : Google Scholar : PubMed/NCBI
8	Jiang XG, Jia JM and Li YS: Simultaneous determination of eight bioactive constituents in shensong yangxin capsule by UPLC. Chinese Herbal Medicines. 5:212–216. 2013.
9	Liu M, Li S, Zhao S, Wang H and Tu P: Studies on excretion kinetics of ten constituents in rat urine after oral administration of Shensong Yangxin Capsule by UPLC-MS/MS. Biomed Chromatogr. 28:525–533. 2014. View Article : Google Scholar
10	Jin ZY, Gong Q and Pu JL: The effect of Shensong Yangxin capsule on the porcine cardiac electrophysiology. Chinese Patent Medicine. 31:471–473. 2009.
11	Li N, Ma KJ, Wu XF, Sun Q, Zhang YH and Pu JL: Effects of Chinese herbs on multiple ion channels in isolated ventricular myocytes. Chin Med J (Engl). 120:1068–1074. 2007.
12	Sun LP, Li N, Wu YL and Pu JL: Effects of Shensong Yangxin capsule on pacemaker channels encoded by human HCN4 gene. Chin Med J (Engl). 123:3148–3150. 2010.
13	Vora A and Kulkami S: Pharmacotherapy to reduce arrhythmic mortality. Indian Heart J. 66(Suppl 1): S113–S119. 2014. View Article : Google Scholar : PubMed/NCBI
14	Yong SL and Wang QK: Animal models for cardiac arrhythmias. Methods Mol Med. 129:127–148. 2006.PubMed/NCBI
15	Di Diego JM and Antzelevitch C: Ischemic ventricular arrhythmias: Experimental models and their clinical relevance. Heart Rhythm. 8:1963–1968. 2011. View Article : Google Scholar : PubMed/NCBI
16	Huggins CE, Bell JR, Pepe S and Delbridge LM: Benchmarking ventricular arrhythmias in the mouse-revisiting the 'Lambeth Conventions' 20 years on. Heart Lung Circ. 17:445–450. 2008. View Article : Google Scholar : PubMed/NCBI
17	Wu H, Tang Q, Yang J, Ye M and Dong W: Atorvastatin ameliorates myocardial ischemia/reperfusion injury through attenuation of endoplasmic reticulum stress-induced apoptosis. Int J Clin Exp Med. 7:4915–4923. 2014.
18	Bochu W, Liancai Z and Qi C: Primary study on the application of serum pharmacology in Chinese traditional medicine. Colloid Surface B Biointerfaces. 43:194–197. 2005. View Article : Google Scholar
19	Graham EL, Balla C, Franchino H, Melman Y, del Monte F and Das S: Isolation, culture, and functional characterization of adult mouse cardiomyoctyes. J Vis Exp. 24:e502892013.
20	Gong DM, Shan HL, Zhou YH, Dong DL and Yang BF: The ion targets of arrhythmias induced by ouabain and aconitine in guinea pig and rat ventricular myocytes. Yao Xue Xue Bao. 39:328–332. 2004.In Chinese. PubMed/NCBI
21	Liang B, Nissen JD, Laursen M, Wang X, Skibsbye L, Hearing MC, Andersen MN, Rasmussen HB, Wickman K, Grunnet M, et al: G-protein-coupled inward rectifier potassium current contributes to ventricular repolarization. Cardiovasc Res. 101:175–184. 2014. View Article : Google Scholar
22	Fang Z, Ren YP, Lu CY, Li Y, Xu Q, Peng L and Fan YY: Effects of sleep deprivation on action potential and transient outward potassium current in ventricular myocytes in rats. Med Sci Monit. 21:542–549. 2015. View Article : Google Scholar : PubMed/NCBI
23	Sun L, Ai J, Wang N, Zhang R, Li J, Zhang T, Wu W, Hang P, Lu Y and Yang B: Cerebral ischemia elicits aberration in myocardium contractile function and intracellular calcium handling. Cell Physiol Biochem. 26:421–530. 2010. View Article : Google Scholar : PubMed/NCBI
24	Billman GE: Novel Therapeutic targets for antiarrhythmic drugs. Wiley; Hoboken, New Jersey: 2010
25	Sun J, Tan BK, Huang SH, Whiteman M and Zhu YZ: Effects of natural products on ischemic heart diseases and cardiovascular system. Acta Pharmacol Sin. 23:1142–1151. 2002.PubMed/NCBI
26	Wang J, Li J and Feng B: Shen Song Yang Xin capsule combined with antiarrhythmic drugs, a new integrative medicine therapy, for the treatment of frequent premature ventricular contractions (FPVC): A-meta analysis of randomized controlled trials. Evid Based Complement Alternat Med. 2014:9767132014. View Article : Google Scholar
27	Chai SB, Wang SR, Yao LF and Wu A: A study of the effect of Shensong Yangxin Capsule on ventricular remodeling after myocardial infarction and isolated heart action potential in rats. Beijing J Tradit Chin Med. 12:967–971. 2009.In Chinese.
28	Wang AH, Pu JL, Qi XY, Miao WL, Hou ZS, Cong HL, Zhou JZ, Liu XF, Li SM, Han QH, et al: Evaluation of shensongyangxin capsule in the treatment of paroxysmal atrial fibrillation: A randomized, double-blind and controlled multicenter trial. Zhonghua Yi Xue Za Zhi. 91:1677–1681. 2011.In Chinese. PubMed/NCBI
29	Roden DM, Balser JR, George AL Jr and Anderson ME: Cardiac ion channels. Annu Rev Physiol. 64:431–475. 2002. View Article : Google Scholar : PubMed/NCBI
30	Isenberg G, Vereecke J, van der Heyden G and Carmeliet E: The shortening of the action potential by DNP in guinea-pig ventricular myocytes is mediated by an increase of a time-independent K conductance. Pflugers Arch. 397:251–259. 1983. View Article : Google Scholar : PubMed/NCBI
31	Vleugels A, Vereecke J and Carmeliet E: Ionic currents during hypoxia in voltage-clamped cat ventricular muscle. Circ Res. 47:501–508. 1980. View Article : Google Scholar : PubMed/NCBI
32	Wit AL and Coromilas J: Role of alterations in refractoriness and conduction in the genesis of reentrant arrhythmias. Implications for antiarrhythmic effects of class III drugs. Am J Cardiol. 72:3F–12F. 1993. View Article : Google Scholar : PubMed/NCBI
33	Fox JJ, McHarg JL and Gilmour RF Jr: Ionic mechanism of electrical alternans. Am J Physiol Heart Circ Physiol. 282:H516–H530. 2002. View Article : Google Scholar : PubMed/NCBI
34	Dhamoon AS and Jalife J: The inward rectifier current (IKl) controls cardiac excitability and is involved in arrhythmogenesis. Heart Rhythm. 2:316–324. 2005. View Article : Google Scholar : PubMed/NCBI
35	Anumonwo JM and Lopatin AN: Cardiac strong inward rectifier potassium channels. J Mol Cell Cardiol. 48:45–54. 2010. View Article : Google Scholar :
36	Li GR and Dong MQ: Pharmacology of cardiac potassium channels. Adv Pharmacol. 59:93–134. 2010. View Article : Google Scholar : PubMed/NCBI