title: Effect of Cardiac Resynchronization Therapy on Myocardial Fibrosis and Relevant Cytokines in a Canine Model With Experimental Heart Failure.
abstract: BACKGROUND
  Though cardiac resynchronization therapy (CRT) has now proved to be effective on cardiac reverse remodeling, data on the underlying molecular changes are limited. The present study aims to investigate the expression of cytokines concerning myocardial fibrosis in dyssynchronous heart failure (HF) and the potential benefits of CRT.
  
  
  RESULTS
  Left bundle branch ablation and rapid pacing was performed to induce a canine model of asynchronous HF. Animals were randomly divided into sham group, HF control group, and CRT group. Echocardiographic data including septum-to-posterior wall motion delay (SPWMD) and standard deviation of the time to peak systolic velocity (Ts-SD) were collected. Histologic samples from lateral left ventricular (LV) and right ventricular (RV) free wall were analyzed and compared among different groups. Serum concentrations of NT-proBNP, TGF-β1, and osteopontin (OPN) were measured using enzyme-linked immunosorbent assay (ELISA). Protein and mRNA expressions of TGF-β1/Smad and OPN from myocardial tissues were also detected and compared. CRT improved cardiac function and corrected intraventricular dyssynchrony with increased LV ejection fraction (LVEF) and decreased SPWMD and Ts-SD (P < 0.05). Histological analysis showed that CRT restored cardiomyocyte diameter (from 4.50 to 6.08 μm) and collagen volume fraction (from 19.33% to 11.21%) of LV (P < 0.01), but had little effect on RV. Serum TGF-β1and OPN level were also reversed toward normal level after CRT (P < 0.05). Compared with sham group, a significantly higher protein and mRNA expressions of TGF-β1/Smad and OPN were observed in HF control group, which were significantly downregulated in CRT group (P < 0.01).
  
  
  CONCLUSIONS
  By means of coordinating LV dyssynchrony, cellular and molecular reverse remodeling relevant to fibrosis inhibition could also be invoked by CRT.
authors.affiliation: Department of Cardiology, Shanghai Institute of Medical Imaging, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Echocardiography, Shanghai Institute of Medical Imaging, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Echocardiography, Shanghai Institute of Medical Imaging, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Shanghai Institute of Medical Imaging, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Shengmei
authors.initials: S
authors.lastname: Qin
authors.affiliation: Department of Echocardiography, Shanghai Institute of Medical Imaging, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Nianwei
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Shanghai Institute of Medical Imaging, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yangang
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Cardiology, Shanghai Institute of Medical Imaging, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000818:Animals; D058406:Cardiac Resynchronization Therapy; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D004195:Disease Models, Animal; D004285:Dogs; D004452:Echocardiography; D005355:Fibrosis; D006333:Heart Failure / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006339:Heart Rate; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D013318:Stroke Volume; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D003094:Collagen
keywords: TGF-β1; cardiac resynchronization therapy; heart failure; left bundle branch block; osteopontin; reverse remodeling