Skip to main content

Advertisement

SpringerLink
Log in

Resveratrol Attenuates Ventricular Arrhythmias and Improves the Long-Term Survival in Rats with Myocardial Infarction

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Objective

The effects of resveratrol treatment on ventricular arrhythmia, survival, and late cardiac remodeling were evaluated in rats with myocardial infarction (MI).

Methods

Three groups of rats (sham-operated, MI, and MI pre-treated with resveratrol) were treated in an in vivo MI model by ligation of left anterior descending coronary artery. The electrocardiogram signals were monitored and recorded for 24 h using an implanted telemetry transmitter. The incidence of ventricular arrhythmias during the first 24-h after MI was also evaluated. Meanwhile, invasive in vivo electrophysiology with pacing in the right ventricle was performed in each group to assess the inducibility of ventricular arrhythmias.

Results

Administration of resveratrol significantly suppressed the MI-induced ventricular tachycardia and ventricular fibrillation (0.4 ± 0.2 in Resv group vs. 7.1 ± 2.2 in MI group episodes per hour per rat, P < 0.01). Data also showed that the incidence of inducible ventricular tachycardia was lower in the Resv group than the MI group (46% vs. 81%, P < 0.01). The infarct size and mortality in the Resv group at 14 weeks were reduced by 20% and 33%, respectively, compared with the MI groups. Results from patch clamp recording revealed that resveratrol inhibited L-type calcium current (I Ca-L), and selectively enhanced ATP-sensitive K+ current (I K,ATP) in a concentration-dependent manner.

Conclusion

These results suggested that the emerging anti-arrhythmic character induced by resveratrol treatment in rat hearts could be mainly accounted for by inhibition of I Ca-L and enhancement of I K,ATP. Administration of resveratrol also improved the long-term survival by suppressing left ventricular remodeling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Jessup M, Brozena S. Heart failure. N Engl J Med. 2003;348:2007–18.

    Article  PubMed  Google Scholar 

  2. Chen PS, Wu TJ, Ting CT, Karagueuzian HS, Garfinkel A, Lin SF, Weiss JN. A tale of two fibrillations. Circulation. 2003;108:2298–303.

    Article  PubMed  Google Scholar 

  3. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444:337–42.

    Article  PubMed  CAS  Google Scholar 

  4. Pataki T, Bak I, Kovacs P, Bagchi D, Das DK, Tosaki A. Grape seed proanthocyanidins improved cardiac recovery during reperfusion after ischemia in isolated rat hearts. Am J Clin Nutr. 2002;75:894–9.

    PubMed  CAS  Google Scholar 

  5. Cui J, Juhasz B, Tosaki A, Maulik N, Das DK. Cardioprotection with grapes. J Cardiovasc Pharmacol. 2002;40:762–9.

    Article  PubMed  CAS  Google Scholar 

  6. Hwang HS, Bleske BE, Ghannam MJ, Converso K, Russell MW, Hunter JC, Boluyt MO. Effects of Hawthorn on cardiac remodeling and left ventricular dysfunction after 1 month of pressure overload-induced cardiac hypertrophy in rats. Cardiovasc Drugs Ther. 2008;22:19–28.

    Article  PubMed  Google Scholar 

  7. Fremont L. Biological effects of resveratrol. Life Sci. 2000;66:663–73.

    Article  PubMed  CAS  Google Scholar 

  8. Chen L, Han Y, Yang F, Zhang T. High-speed counter-current chromatography separation and purification of resveratrol and piceid from Polygonum cuspidatum. J Chromatogr A. 2001;907:343–6.

    Article  PubMed  CAS  Google Scholar 

  9. Fukao H, Ijiri Y, Miura M. Effect of transresveratrol on the thrombogenicity and atherogenicity in apolipoprotein-deficient and low-density lipoprotein receptor-deficient mice. Blood Coagul Fibrinolysis. 2004;15:441–6.

    Article  PubMed  CAS  Google Scholar 

  10. Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275:218–20.

    Article  PubMed  CAS  Google Scholar 

  11. Donnelly LE, Newton R, Kennedy GE, Fenwick PS, Leung RHF, Ito K, et al. Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms. Am J Physiol Lung Cell Mol Physiol. 2004;287:L774–83.

    Article  PubMed  CAS  Google Scholar 

  12. Ray PS, Maulik G, Cordis GA, Bertelli AA, Bertelli A, Das DK. The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Radic Biol Med. 1999;27:160–9.

    Article  PubMed  CAS  Google Scholar 

  13. Lekli I, Szabo G, juhasz B, Das S, Das M, Varga E, et al. Protective mechanisms of resveratrol against ischemia–reperfusion-induced damage in hearts obtained from Zucker obese rats: the role of GLUT-4 and endothelin. Am J Physiol Heart Circ Physiol. 2008;294:H859–66.

    Article  PubMed  CAS  Google Scholar 

  14. Mokni M, Limam F, Elkahoui S, Amri M, Aouani E. Strong cardioprotective effect of resveratrol, a red wine polyphenol, on isolated rat hearts after ischemia/reperfusion injury. Arch Biochem Biophys. 2007;457:1–6.

    Article  PubMed  CAS  Google Scholar 

  15. Liew R, Stagg MA, MacLeod K, Collins P. The red wine polyphenol, resveratrol, exerts acute direct actions on guinea-pig ventricular myocytes. Eur J Pharmacol. 2005;519:1–9.

    Article  PubMed  CAS  Google Scholar 

  16. Wallace C, Baczko I, Jones L, Fercho M, Light PE. Inhibition of cardiac voltage-gated sodium channels by grape polyphenols. Br J Pharmacol. 2006;149:657–65.

    Article  PubMed  CAS  Google Scholar 

  17. Chen WP, Su MJ, Hung LM. In vitro electrophysiological mechanisms for antiarrhythmic efficacy of resveratrol, a red wine antioxidant. Eur J Pharmacol. 2007;554:196–214.

    Article  PubMed  CAS  Google Scholar 

  18. Cai J, Yi FF, Yang XC, Lin GS, Jiang H, Wang T, Xia Z. Transplantation of embryonic stem cell-derived cardiomyocytes improves cardiac function in infracted rat hearts. Cytotherapy. 2007;9:283–91.

    Article  PubMed  CAS  Google Scholar 

  19. Opitz CF, Mitchell GF, Pfeffer MA, Pfeffer JM. Arrhythmias and death after coronary artery occlusion in the rat: continuous telemetric ECG monitoring in conscious, untethered rats. Circulation. 1995;92:253–61.

    PubMed  CAS  Google Scholar 

  20. Cai J, Yi FF, Yang XC, Song J, Jiang XJ, Jiang H, et al. Adenoviral gene transfer of HCN4 creates a genetic pacemaker in pigs with complete atrioventricular block. Life Sci. 2007;80:1746–53.

    Article  PubMed  CAS  Google Scholar 

  21. Carmeliet E. Cardiac ionic currents and acute ischemia: from channels to arrhythmias. Phys Rev. 1999;79:917–1017.

    CAS  Google Scholar 

  22. Cole WC, McPherson CD, Sontag D. ATP-regulated K+ channels protect the myocardium against ischemic/reperfusion damage. Circ Res. 1991;69:571–81.

    PubMed  CAS  Google Scholar 

  23. Das S, Alagappan VK, Bagchi D, Sharma HS, Maulik N, Das DK. Coordinated induction of iNOS-VEGF-KDR-eNOS after resveratrol consumption: a potential mechanism for resveratrol preconditioning of the heart. Vascul Pharmacol. 2005;42:281–9.

    Article  PubMed  CAS  Google Scholar 

  24. Zhang l, Yin J, Liu Z, Zhang Y, Wang Q, Zhao J. Effect of resveratrol on L-type calcium current in rat ventricular myocytes. Acta Pharmacol Sin. 2006;27:179–83.

    Article  PubMed  CAS  Google Scholar 

  25. Zhang Y, Liu Y, Wang T, Li B, Li H, Wang Z, Yang B. Resveratrol, a natural ingredient of grape skin: antiarrhythmic efficacy and ionic mechanisms. Biochem Biophys Res Commun. 2006;340:1192–9.

    Article  PubMed  CAS  Google Scholar 

  26. Buluc M, Ayaz M, Tulan B, Demirel-Yilmaz E. Resveratrol-induced depression of the mechanical and electrical activity of rat heart is reversed by Glyburide: evidence for possible KATP channels activation. Arch Pharm Res. 2007;30:603–7.

    Article  PubMed  CAS  Google Scholar 

  27. Nichols C, Ripoll C, Lederer W. ATP-sensitive potassium channel modulation of the guinea pig ventricular action potential and contraction. Circ Res. 1991;68:280–7.

    PubMed  CAS  Google Scholar 

  28. Lee TM, Lin MS, Tsai CH, Chang NC. Effects of pravastatin on ventricular remodeling by activation of myocardial KATP channels in infracted rats: role of 70-kDa S6 kinase. Basic Res Cardiol. 2007;102:171–82.

    Article  PubMed  CAS  Google Scholar 

  29. Bak I, Papp G, Turoczi T, Varga E, Szendrei L, Joo F, Tosaki A. The role of heme oxygenase-related carbon monoxide and ventricular fibrillation in ischemic/reperfused hearts. Free Radic Biol Med. 2002;33:639–48.

    Article  PubMed  CAS  Google Scholar 

  30. Bak I, Szendrei L, Turoczi T, Papp G, Joo F, Das DK. Heme oxygenase-1 related carbon monoxide production and ventricular fibrillation in isolated ischemic/reperfused mouse myocardium. FASEB J. 2003;17:2133–5.

    PubMed  CAS  Google Scholar 

  31. Hung LM, Su MJ, Chen JK. Resveratrol protects myocardial ischemia–reperfusion injury through both NO-dependent and NO independent mechanisms. Free Radic Biol Med. 2004;36:774–81.

    Article  PubMed  CAS  Google Scholar 

  32. Juric D, Wojciechowski P, Das DK, Netticadan T. Prevention of concentric hypertrophy and diastolic impairment in aortic-banded rats treated with resveratrol. Am J Physiol Heart Circ Physiol. 2007;292:H2138–43.

    Article  PubMed  CAS  Google Scholar 

  33. Berk BC, Fujiwara K, Lehoux S. ECM remodeling in hypertensive heart disease. J Clin Invest. 2007;117:568–75.

    Article  PubMed  CAS  Google Scholar 

  34. Burstein B, Maguy A, Clement R, Gosselin H, Poulin F, Ethier N, et al. Effects of resveratrol (trans-3,5,4-trihydroxystilbene) treatment on cardiac remodeling following myocardial infarction. J Pharmacol Exp Ther. 2007;323:916–23.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Ting Zhu (Massachusettes General Hospital, Harvard Medical School) for review of the manuscript and helpful comments. This work was supported by grants from National Natural Science Foundation of China (No.30600337 and No. 30770875).

Author information

Authors and Affiliations

  1. Department of Cardiology, The Second Affiliated Hospital to Medical College, Shantou University, Shantou, 515041, People’s Republic of China

    You-Ren Chen

  2. Department of Cardiology, Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China

    Fang-Fang Yi, Xin-Chun Yang, Pi-Xiong Su & Jun Cai

  3. Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China

    Xin-Yi Li & Cheng-Yao Wang

  4. Center for Molecular Development and Disease, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Baylor College of Medicine, Houston, TX, 77030, USA

    Li Chen

  5. Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA, 02129, USA

    Jun Cai

Authors
  1. You-Ren Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fang-Fang Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin-Yi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cheng-Yao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xin-Chun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pi-Xiong Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jun Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Pi-Xiong Su or Jun Cai.

Additional information

You-Ren Chen and Fang-Fang Yi contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, YR., Yi, FF., Li, XY. et al. Resveratrol Attenuates Ventricular Arrhythmias and Improves the Long-Term Survival in Rats with Myocardial Infarction. Cardiovasc Drugs Ther 22, 479–485 (2008). https://doi.org/10.1007/s10557-008-6141-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-008-6141-8

Key words

Search

Navigation