title: Myosin cross-bridge dynamics in patients with hypertension and concentric left ventricular remodeling.
abstract: BACKGROUND
  Hypertension (HTN) causes concentric left ventricular remodeling, defined as an increased relative wall thickness or overt left ventricular hypertrophy, and associated diastolic dysfunction. HTN and concentric remodeling are also common precursors to heart failure with a preserved ejection fraction. It is not known whether the myofilament contributes to diastolic dysfunction in patients with concentric remodeling.
  
  
  RESULTS
  Intraoperative myocardial biopsies were obtained in 15 male patients undergoing coronary bypass grafting, all with normal left ventricular ejection fraction and wall motion. Eight patients had a history of HTN and concentric remodeling. Seven without HTN or remodeling served as controls. Myocardial strips were dissected and demembranated with detergent. Isometric tension was measured and sinusoidal length perturbation analysis performed at sarcomere length 2.2 μm and pCa 8 to 4.5. Sinusoidal analysis provides estimates of cross-bridge dynamics, including rate constants of attachment and detachment and cross-bridge attachment time. The normalized isometric tension-pCa relation was similar in HTN and controls. However, cross-bridge attachment time was significantly prolonged at submaximal [Ca(2+)] (pCa ≥6.5) in HTN patients. Analysis of protein phosphorylation revealed ≈25% reduction in phosphorylation of troponin I in HTN patients (P<0.05).
  
  
  CONCLUSIONS
  Compared with controls, patients with HTN and concentric remodeling display prolonged cross-bridge attachment time at submaximal [Ca(2+)] without a change in the tension-pCa relation. Prolonged cross-bridge attachment time implicates altered cross-bridge dynamics as a cause of slowed relaxation in these patients. This finding was associated with reduced phosphorylation of troponin I, suggesting decreased phosphorylation of protein kinase A/G sites as a mechanism.
authors.affiliation: Cardiology Unit, University of Vermont, Burlington, VT, USA.
authors.forename: Cameron
authors.initials: C
authors.lastname: Donaldson
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Palmer
authors.forename: Michael
authors.initials: M
authors.lastname: Zile
authors.forename: David W
authors.initials: DW
authors.lastname: Maughan
authors.forename: John S
authors.initials: JS
authors.lastname: Ikonomidis
authors.forename: Henk
authors.initials: H
authors.lastname: Granzier
authors.forename: Markus
authors.initials: M
authors.lastname: Meyer
authors.forename: Peter
authors.initials: P
authors.lastname: VanBuren
authors.forename: Martin M
authors.initials: MM
authors.lastname: LeWinter
mesh_terms: D000368:Aged; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000601:surgery; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009218:Myosins / Q000502:physiology*; D010766:Phosphorylation; D019210:Troponin I / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D019210:Troponin I; D009218:Myosins; D002118:Calcium