title: Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model.
abstract: OBJECTIVE
  Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has been shown to exert beneficial effects in heart failure. The purpose of this study was to test whether sildenafil suppressed transverse-tubule (T-tubule) remodeling in left ventricular (LV) failure and thereby providing the therapeutic benefits.
  
  
  METHODS
  A pressure overload-induced murine heart failure model was established in mice by thoracic aortic banding (TAB). One day after TAB, the mice received sildenafil (100 mg·kg(-1)·d(-1), sc) or saline for 5 weeks. At the end of treatment, echocardiography was used to examine LV function. Then the intact hearts were dissected out and placed in Langendorff-perfusion chamber for in situ confocal imaging of T-tubule ultrastructure from epicardial myocytes.
  
  
  RESULTS
  TAB surgery resulted in heart failure accompanied by remarkable T-tubule remodeling. Sildenafil treatment significantly attenuated TAB-induced cardiac hypertrophy and congestive heart failure, improved LV contractile function, and preserved T-tubule integrity in LV cardiomyocytes. But sildenafil treatment did not significantly affect the chamber dilation. The integrity of LV T-tubule structure was correlated with cardiac hypertrophy (R(2)=0.74, P<0.01) and global LV function (R(2)=0.47, P<0.01).
  
  
  CONCLUSIONS
  Sildenafil effectively ameliorates LV T-tubule remodeling in TAB mice, revealing a novel mechanism underlying the therapeutic benefits of sildenafil in heart failure.
authors.affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.|Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Chun-kai
authors.initials: CK
authors.lastname: Huang
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Bi-yi
authors.initials: BY
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Ang
authors.initials: A
authors.lastname: Guo
authors.affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.|Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.|Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Yan-qi
authors.initials: YQ
authors.lastname: Zhu
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: William
authors.initials: W
authors.lastname: Kutschke
authors.affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Hong
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA.|Department of Veterans Affairs Medical Center, Iowa City, IA 52242, USA.
authors.forename: Long-sheng
authors.initials: LS
authors.lastname: Song
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy / Q000473:pathology; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D000068677:Sildenafil Citrate / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate