Resveratrol, a natural ingredient of grape skin: Antiarrhythmic efficacy and ionic mechanisms Yan Zhang a , Yanyan Liu a , Tao Wang a , Baoxin Li a , Houwei Li c , Zhiguo Wang d, * , Baofeng Yang a,b, * a Department of Pharmacology, Harbin Medical University, PR China b Bio-Pharmaceutical Key Laboratory of Heilongjiang Province-Incubator of State Key Laboratory, Harbin 150086, PR China c Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, PR China d Research Center, Montreal Heart Institute, Canada Received 10 December 2005 Available online 4 January 2006 Abstract Resveratrol has been demonstrated to produce a variety of biological actions. Accumulating line of evidence supported the view that resveratrol may exert protective effect on the cardiovascular system. The aim of the study was to assess the antiarrhythmic profile as well as electrophysiological properties of resveratrol. We observe the antiarrhythmic effect of resveratrol on aconitine induced rat arrhythmia, ouabain induced guinea pig arrhythmia, and coronary ligation induced rat arrhythmia animal models. Resveratrol significantly and dose-dependently increased the doses of aconitine and ouabain required to induce the arrhythmia indexes. In coronary ligation induced rat arrhythmia model, resveratrol shortened duration of arrhythmia, decreased incidence of ventricular tachycardia and mortality. Elec- trophysiological experiment revealed that resveratrol could shorten APD through inhibition of I Ca and selective enhancement of I Ks without an effect on I Kr . Ó 2005 Elsevier Inc. All rights reserved. Keywords: Arrhythmia; Resveratrol; Arrhythmia animal model; Electrophysiological property Cardiac arrhythmia remains a serious problem despite intensive research in recent years. Ventricular tachycardia may even culminate in sudden cardiac death. Class I anti- arrhythmic drugs have been used for the treatment of life-threatening ventricular tachyarrhythmias. However, the effectiveness of the most currently used drugs has always been limited by their serious cardiac depression or proarrhythmic effects. The CAST (1989) study provided evidence that some class I C agents (such as flecainide and encainide) significantly increased postinfarction mortality. Thus, the role of class I drugs in controlling serious arrhythmias is diminishing [1–3]. In the search for new drugs with a more favourable benefit-risk ratio, substances that prolong the cardiac APD and, as a result, the effective refractory perion (ERP) (class III like drugs) have received considerable attention as potential antiarrhythmic agents. The antiarrhythmic benefit afforded by class III agents is proposed to result from sufficient prolongation of myocar- dial refractoriness for the wavelength activation to exceed the path length of the reentrant circuit, thereby preventing the initiation or maintenance of re-entrant excitation [4,5]. Clinical results with d-sotalol, a ‘‘pure’’ class III agent, however, highlighted the limited utility of this type of agent, because it causes torsade de pointes arrhythmias, and may even increase mortality in subsets of patients with myocardial infarction and lowered ejection fraction [6]. Accordingly, the search for new types of antiarrhythmic drugs to treat such life-threatening arrhythmias remains an important area. More recently, there has also been 0006-291X/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.bbrc.2005.12.124 * Corresponding authors. Fax: +0086 0451 86675769 (B. Yang); +1 514 376 1355 (Z. Wang). E-mail addresses: zhiguo.wang@ice-mhi.org (Z. Wang), yangbf@ems. harmu.edu.cn (B. Yang). www.elsevier.com/locate/ybbrc Biochemical and Biophysical Research Communications 340 (2006) 1192–1199 BBRC