title: Cardiac arrhythmogenic remodeling in a rat model of long-term intensive exercise training.
abstract: BACKGROUND
  Recent clinical studies suggest that endurance sports may promote cardiac arrhythmias. The aim of this study was to use an animal model to evaluate whether sustained intensive exercise training induces potentially adverse myocardial remodeling and thus creates a potential substrate for arrhythmias.
  
  
  RESULTS
  Male Wistar rats were conditioned to run vigorously for 4, 8, and 16 weeks; time-matched sedentary rats served as controls. Serial echocardiograms and in vivo electrophysiological studies at 16 weeks were obtained in both groups. After euthanasia, ventricular collagen deposition was quantified by histological and biochemical studies, and messenger RNA and protein expression of transforming growth factor-β1, fibronectin-1, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, procollagen-I, and procollagen-III was evaluated in all 4 cardiac chambers. At 16 weeks, exercise rats developed eccentric hypertrophy and diastolic dysfunction, together with atrial dilation. In addition, collagen deposition in the right ventricle and messenger RNA and protein expression of fibrosis markers in both atria and right ventricle were significantly greater in exercise than in sedentary rats at 16 weeks. Ventricular tachycardia could be induced in 5 of 12 exercise rats (42%) and only 1 of 16 sedentary rats (6%; P=0.05). The fibrotic changes caused by 16 weeks of intensive exercise were reversed after an 8-week exercise cessation.
  
  
  CONCLUSIONS
  In this animal model, we documented cardiac fibrosis after long-term intensive exercise training, together with changes in ventricular function and increased arrhythmia inducibility. If our findings are confirmed in humans, the results would support the notion that long-term vigorous endurance exercise training may in some cases promote adverse remodeling and produce a substrate for cardiac arrhythmias.
authors.affiliation: Thorax Institute, Hospital Clinic, Universitat de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Benito
authors.forename: Gemma
authors.initials: G
authors.lastname: Gay-Jordi
authors.forename: Anna
authors.initials: A
authors.lastname: Serrano-Mollar
authors.forename: Eduard
authors.initials: E
authors.lastname: Guasch
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Shi
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.forename: Josep
authors.initials: J
authors.lastname: Brugada
authors.forename: Stanley
authors.initials: S
authors.lastname: Nattel
authors.forename: Lluis
authors.initials: L
authors.lastname: Mont
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D023421:Models, Animal; D010805:Physical Conditioning, Animal / Q000009:adverse effects / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D020257:Ventricular Remodeling / Q000502:physiology*