Effect of Resveratrol Preconditioning on Myocardial Dysfunction after Cardiac Arrest in Rats

ZHANG Hai-hong, CAO Yu, ZENG Zhi

Abstract

To investigate the protective effects and its potential mechanism of resveratrol preconditioning on rat cardiac arrest after return of spontaneous circulation (ROSC) with the study of hemodynamic parameters and nitrative stress in myocardium. Methods Cardiac arrest SPF SD rat model was established by transoesophageal cardiac alternating current stimulation. Intervention was implemented 15 min before cardiac arrest. Twenty four rats with ROSC after cardiac arrest were randomly assigned into five groups: vehicle, sham, resveratrol 2.3 mg/kg (A group), resveratrol 0.23 mg/kg (B group) and resveratrol 0.023 mg/kg (C group). Heart rate, mean arterial pressure, and left ventricular variables (+dp/dtmax and -dp/dtmin) were recorded in 0.5 h, 1.0 h, 2.0 h, 3.0 h, and 4.0 h respectively. Rats were sacrificed at 4 h after ROSC, and hearts were removed for determining expression of inducible nitric oxide synthase (iNOS) protein, myocardial peroxynitrite, and nitrotyrosine. Results Global ROSC rate was 72.7% after the induction of cardiac arrest. Resveratrol preconditioning did not improve ROSC rate significantly. Heart rate and blood pressure declined at early phase of ROSC, then heart rate recovered to the baseline value, but blood pressure still declined progressively. There were no significant differences between resveratrol groups and vehicle group. Myocardial function worsened progressively even after ROSC. Resveratrol improved cardiac function significantly，especially in lower concentration groups. Myocardial iNOS expression, peroxynitrite, and nitrotyrosine content increased significantly after ROSC. Resveratrol decreased these products significantly, and lower concentration groups did better. Conclusion Resveratrol preconditioning could improve cardiac dysfunction after ROSC, which may be associated with its inhibitory effect on nitrative stress.

 

Keywords: Cardiac arrest, Cardiopulmonary resuscitation, Resveratrol Nitrative stress 

 

Full Text:

PDF


References


Hua W, Zhang LF, Wu YF, et al. Incidence of sudden cardiac arrest in China: analysis of 4 regional populations. J Am Coll Cardiol, 2009;54( 12): 1110-1118.

Langhelle A, Tyvold SS, Lexow K, et al. In-hospital factors associated with improved outcomes after out-of-hospital cardiac arrest. A comparison between four regions in Norway. Resusciation. 2003 ; 56(3); 247-263.

Neumar RW, Nolan JP. Adrie C, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication: a consensus statement from the International Liaison Committee on Resuscitation ( American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council. Heart and Stroke Foundation of Canada, Inter American Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa) ;the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia;the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council. Circulation»2008; 118(23):2452-2483.

Moncada S, Higgs A. L-Arginine-nitric oxide pathway. N Engl J Med, 1993;329(27):2002-2012.

Kern KB, Berg RA, Hilwig RW. et al. Myocardial cytokine IL-8 and nitric oxide synthase activity during and after resuscitation; preliminary observations in regards to post-resuscitation myocardial dysfunction. Resuscitation, 2008; 77 (3) ;401-409.

Hung LM, Chen JK. Huang SS, et al. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardio Res,2000;47(3): 549-555.

Belguendouz I. Fremont L, Gozzalino MT. Interaction of transresveratrol with plasma lipoproteins. Biochem Pharmacol. 1998;55(6):811 -816.

Kern KB. Zuercher M. Cragun D, et at. Myocardial microcirculatory dysfunction after prolonged ventricular fibrillation and resuscitation. Crit Care Med. 2008; 36 ( 11 Suppl): S418-S421.

Rivers EP. Wortsman J, Rady MY. et al. The effect of the total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period. Chest, 1994 ; 106(5): 1499-1507.

Youngquist ST, Niemann JT, Shah AP, et al. A comparison of etanercept vs. infliximab for the treatment of post-arrest myocardial dysfunction in a swine model of ventricular fibrillation. Resuscitation,2013;84(7):999-1003.

Dolinsky VW. Dyck JR. Calorie restriction and resveratrol in cardiovascular health and disease. Biochim Biophys Acta,2011; 1812(11):1477-1489.

Kern KB. Hilwig RW. Rhee KH, et al. Myocardial dysfunction after resuscitation from cardiac arrest; an example of global myocardial stunning. J Am Coll Cardiol, 1996;28( 1) ; 232-240.

Chalkias A, Xanthos T. Pathophysiology and pathogenesis of post-resuscitation myocardial stunning. Heart Fail Rev, 2012; 17(1);117-128.

Mukherjee S, Dudley JI, Das DK. Dose-dependency of resveratrol in providing health benefits. Dose Response,2010;8(4) : 478-500.

Goh SS, Woodman OL, Pepe S, et al. The red wine antioxidant resveratrol prevents cardiomyocyte injury following ischemia-reperfusion via multiple sites and mechanisms. Antioxid Redox Signal,2007;9( 1): 101-113.

Shen M, Jia GL, Wang YM, et al. Cardioprotective effect of resvaratrol pretreatment on myocardial ischemia-reperfusion induced injury in rats. Vascul Pharmacol,2006 ;45(2): 122-126.

Han F, Da T, Riobo NA, et al. Early mitochondrial dysfunction in electron transfer activity and reactive oxygen species generation after cardiac arrest. Crit Care Med. 2008; 36 (11 Suppl) ;S447-S453.

Zia A, Kern KB. Management of postcardiac arrest myocardial dysfunction. Curr Opin Crit Care,2011; 17(3): 241-246.

Marechal A, Mattioli ТА, Stuehr DJ, et al. Activation of peroxynitrite by inducible nitric-oxide synthase:a direct source of nitrative stress. J Biol Chem.2007;282(19); 14101-14112. Wu I). Bassuk J, Arias J, et и/. Different roles of nitric oxide synthase isoforms in cardiopulmonary resuscitation in pigs. Resuscitation»2007;73(1): 144-153.

Tao L, Gao E, Jiao X. etal. Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation. 2007; 115 ( 11 ); 1408- 1416.

Hung LM, Su MJ, Chen JK. Resveratrol protects myocardial ischemia-reperfusion injury through both N()-dependent and NO-independent mechanisms. Free Radic Biol Med. 2004; 36 (6):7 74-7 81.

Mokni M. Li mam F, Elkahoui S ,et al. Strong cardioprotective effect of resveratrol. a red wine polyphenol, on isolated rat hearts after ischemia/reperfusion injury. Arch Biochem Biophys.2007;457(1) : 1-6.

Hattori R. Otani H, Maulik N. et al. Pharmacological preconditioning with resveratrol; role of nitric oxide. Am J Physiol Heart Circ Physiol.2002;282(6): H1988-H1995.

Imamura G, Bertelli A A, Bertelli A, et al. Pharmacological preconditioning with resveratrol; an insight with iNOS knockout mice. Am J Physiol Heart Circ Physiol,2002;282(6); H1996-H2003.


Refbacks

  • There are currently no refbacks.