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Despite the electrophysiological mechanisms, cardiac re-entry has been regarded as an important mechanism causing malignant arrhythmias. In the present study, SSYX was shown to significantly prolong action potentials and slow cardiac repolarization. An appropriate extension of the action potential is conducive to increasing the refractory period and reducing myocardial excitability and re-entry Therefore, the results of the present study suggested that SSYX altered the myocardial refractoriness and conductivity, and exerted a therapeutic effect on ischemic arrhythmias.

Ischemia and hypoxia interfere with ion channels, and predispose individuals to a disturbed cardiac rhythm I K1 is a strong inward rectification current, which stabilizes the membrane potential and is involved in the third period of action potential repolarization. I to is the primary outward current of the cardiac rapid repolarization.

Following depolarization, the inward sodium current I Na becomes inactivated, and I to initiates the rapid repolarization of the action potentials 34 — Therefore, I K1 and I to are both involved in cardiac repolarization, and are associated with cardiac excitability and arrhythmogenesis. In the present study, SSYX significantly decreased the densities of I to , suppressed the first period of action potential repolarization and contributed to a prolongation of the myocardial action potential.

Furthermore, inhibition of I to reduced the high irregularity of ischemic myocardial repolarization and the formation of re-entrant excitability, which helped to suppress re-entry and avoid the induction of Torsades de Pointes. Similarly, SSYX inhibited the inward current of I K1 significantly without affecting its reversal potential and rectification properties. This inhibitory effect was conductive to automatically eliminating the fourth period of action potential depolarization and inhibiting delayed afterdepolarization DAD.

Traditional pharmacology for TCM involves directly exposing cells, tissues or organs to the crude drug. However, due to the complexities of drug absorption and metabolism associated with TCM, the efficacy of the drug in its crude form may not be as good as the active ingredients after in vivo metabolism of the drug. Therefore, serum pharmacology for TCM was adopted in the present study. Serum pharmacology facilitates the direct application of active ingredients after the in vivo metabolism of the TCM, and utilizes cytological and molecular biological methods, thereby providing a conjunction of modern scientific technology and TCM research.

In addition, observing and analyzing the processes of absorption and metabolism of drugs is beneficial in terms of eliminating the influence of various interference factors that are associated with in vitro experiments. Incubating myocytes with serum containing SSYX also corroborated previous findings on the efficacy of SSYX identified by means of in vivo and in vitro experiments.

Serum pharmacology thus provides a novel approach for developing antiarrhythmic TCMs. In conclusion, SSYX effectively prevents ischemic arrhythmias. In addition, SSYX is potent in extending action potentials and in inhibiting I to and I K1 , thereby decreasing myocardial autorhythmicity and re-entrant excitability.

Therefore, SSYX may be used as an effective drug to treat ischemic arrhythmias. Neth Heart J. Cell Physiol Biochem. Davies MJ: Pathological view of sudden cardiac death. Br Heart J. Am J Physiol. Chinese Herbal Medicines. Biomed Chromatogr. View Article : Google Scholar. Chinese Patent Medicine. Chin Med J Engl. Vora A and Kulkami S: Pharmacotherapy to reduce arrhythmic mortality. Indian Heart J.

Methods Mol Med. Heart Rhythm.

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Cardiac Na+ Channels as Therapeutic Targets for Antiarrhythmic Agents

Heart Lung Circ. Int J Clin Exp Med. Colloid Surface B Biointerfaces. J Vis Exp. Yao Xue Xue Bao. In Chinese. Cardiovasc Res. Med Sci Monit. Billman GE: Novel Therapeutic targets for antiarrhythmic drugs. Wiley; Hoboken, New Jersey: Acta Pharmacol Sin. Evid Based Complement Alternat Med. Beijing J Tradit Chin Med. Zhonghua Yi Xue Za Zhi. Annu Rev Physiol. Pflugers Arch. Circ Res. 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.

Abbreviations

J Mol Cell Cardiol. View Article : Google Scholar :. Adv Pharmacol. June Volume 13 Issue 6.

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Antiarrhythmic Drug Therapy 1

Register Login. Molecular Medicine Reports. Cited By CrossRef : 0 citations. This article is mentioned in:. 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. 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.

Introduction Despite numerous previous advances in the treatment of cardiovascular disease, sudden cardiac death caused by ischemic arrhythmias remains a major reason of mortality worldwide 1. Whole-cell patch-clamp recording Serum preparation Serum containing SSYX was prepared according to a previously described method Separation and isolation of cardiomyocytes Cardiomyocytes were isolated from the rat hearts by enzymatic dissociation Results SSYX prevents ischemic arrhythmias Electrocardiogram and heart rate were continuously recorded for 30 min following ligating coronary artery.

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