title: Resveratrol preserves myocardial function and perfusion in remote nonischemic myocardium in a swine model of metabolic syndrome.
abstract: BACKGROUND
  Resveratrol has been shown to reverse some of the detrimental effects of metabolic syndrome (MetS). We sought to define the impact of supplemental resveratrol on normal myocardium remote from an ischemic territory in a swine model of MetS and chronic myocardial ischemia.
  
  
  METHODS
  Yorkshire swine were fed a normal diet (control), a high cholesterol diet (HCD), or a high cholesterol diet with orally supplemented resveratrol (HCD-R; 100 mg/kg/day). Four weeks after diet modification, myocardial ischemia was induced by ameroid constrictor placement. Seven weeks later, myocardial tissue from a territory remote from the ischemia was harvested. Animals in the HCD and HCD-R groups underwent functional cardiac MRI before ischemia and before sacrifice. Tissue was harvested for protein expression analysis.
  
  
  RESULTS
  After 7 weeks of ischemia, regional left ventricular systolic function was significantly increased in HCD-R as compared with HCD animals. During ventricular pacing the HCD group had significantly decreased flow (p = 0.03); perfusion in the HCD-R was preserved as compared with the control. There was no difference in microvascular relaxation. Expression of metabolic proteins Sirt-1 (p = 0.002), AMPkinase (p = 0.02), and carnitine palmitoyltransferase-I (p = 0.002) were upregulated in the HCD-R group. Levels of protein oxidative stress were significantly increased in the HCD and HCD-R groups, as compared with the controls (p = 0.003). Activated endothelial nitric oxide synthase (eNOS) was increased in the HCD-R group (p = 0.01). There was no difference in myocardial endothelial cell density between the groups; however, dividing endothelial cells were decreased in the HCD and HCD-R groups (p = 0.006).
  
  
  CONCLUSIONS
  Resveratrol supplementation improves regional left ventricular function and preserves perfusion to myocardium remote from an area of ischemia in an animal model of metabolic syndrome and chronic myocardial ischemia.
authors.affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Robich
authors.forename: Louis M
authors.initials: LM
authors.lastname: Chu
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Burgess
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Yuchi
authors.initials: Y
authors.lastname: Han
authors.forename: Reza
authors.initials: R
authors.lastname: Nezafat
authors.forename: Michael P
authors.initials: MP
authors.lastname: Leber
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Laham
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Manning
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D003331:Coronary Vessels / Q000187:drug effects*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006321:Heart; D008279:Magnetic Resonance Imaging; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy*; D017202:Myocardial Ischemia / Q000209:etiology; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D013267:Stilbenes; D000077185:Resveratrol