title: Selective Heart Rate Reduction Improves Metabolic Syndrome-related Left Ventricular Diastolic Dysfunction.
abstract: BACKGROUND
  Enhanced heart rate observed in metabolic syndrome (MS) contributes to the deterioration of left ventricular (LV) function via impaired LV filling and relaxation, increased myocardial O2 consumption, and reduced coronary perfusion. However, whether heart rate reduction (HRR) opposes LV dysfunction observed in MS is unknown.
  
  
  METHODS
  We assessed in Zucker fa/fa rats, a rat model of MS, the cardiovascular effects of HRR induced by the If current inhibitor S38844 (3 mg · kg(-1) · d(-1)).
  
  
  RESULTS
  Delayed short-term (4 days) and long-term (90 days) HRR induced by S38844 reduced LV end-diastolic pressure and LV end-diastolic pressure-volume relation, increased myocardial tissue perfusion, decreased myocardial oxidized glutathione levels, and preserved cardiac output, without modifying LV end-systolic pressure and LV end-systolic pressure-volume relation, although only long-term S38844 opposed LV collagen accumulation. Long-term S38844 improved flow-induced endothelium-dependent dilatation of mesenteric arteries, while metabolic parameters, such as plasma glucose levels, and Hb1c, were never modified.
  
  
  CONCLUSIONS
  In rats with MS, HRR induced by the If inhibitor S38844 improved LV diastolic function and endothelium-dependent vascular dilatation, independent from modifications in metabolic status. Moreover, this improvement in cardiac function involves not only immediate effects such as improved myocardial perfusion and reduced oxidative stress but also long-term effects such as modifications in the myocardial structure.
authors.affiliation: *Institut National de la Santé et de la Recherche Médicale U1096, Rouen, France; †Institute for Research and Innovation in Biomedicine, Rouen, France; ‡UFR de Médecine et Pharmacie, Rouen University, Rouen, France; §Plateau d'Imagerie CardioThoracique de l'Universite de Rouen, Rouen, France; ¶Equipe d'Acceuil 4651, Aliment Bioprocedes Toxicologie Environnement, Rouen, France; ‖Bruker Biospin MRI GMBH, Ettlingen, Germany; and **Servier, Suresnes, France.
authors.forename: Nassiba
authors.initials: N
authors.lastname: Merabet
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Fang
authors.forename: Lionel
authors.initials: L
authors.lastname: Nicol
authors.forename: Christelle
authors.initials: C
authors.lastname: Monteil
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rémy-Jouet
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Henry
authors.forename: Didier
authors.initials: D
authors.lastname: Wecker
authors.forename: Sabrina
authors.initials: S
authors.lastname: Le Bouter-Banon
authors.forename: Jerome
authors.initials: J
authors.lastname: Roussel
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
authors.forename: Paul
authors.initials: P
authors.lastname: Mulder
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003971:Diastole / Q000187:drug effects; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D011924:Rats, Zucker; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D002317:Cardiovascular Agents; D007473:Ion Channels