title: Cardiac resynchronization by cardiosphere-derived stem cell transplantation in an experimental model of myocardial infarction.
abstract: BACKGROUND
  Cardiosphere-derived stem cell (CDC) transplantation can improve global left ventricular ejection fraction (LVEF) after myocardial infarction (MI). The aim of this study was to examine the effects of CDC transplantation on regional function and dyssynchrony after MI.
  
  
  METHODS
  Two million rat CDCs (n = 7) or phosphate-buffered saline (n = 7) was injected into the infarct regions of Wistar Kyoto rats. Infarct size and CDC localization were evaluated by positron emission tomography (n = 7). Two-dimensional and strain echocardiography were performed at 1 and 4 weeks after MI. LVEF, circumferential strain, and time to peak circumferential strain were measured in the basal and apical short-axis views. Dyssynchrony was defined as the maximal difference of time to peak circumferential strain of opposing segments in each short-axis view. Engraftment was measured by quantitative polymerase chain reaction.
  
  
  RESULTS
  Positron emission tomography revealed that infarct size was 15.4 ± 3.6% of the left ventricle and that CDCs were localized to the infarct and border zone. CDC transplantation improved mean LVEF (45 ± 8% to 52 ± 7%, P = .02), mean circumferential strain (-7 ± 2% to -10 ± 1%, P = .02), and mean dyssynchrony (45 ± 10 to 28 ± 11 m sec, P = .04) of the infarct/peri-infarct zone from 1 to 4 weeks after MI, despite CDC engraftment of only 2.4 ± 3%. In contrast, mean LVEF (48 ± 5% to 40 ± 4%, P = .03) and mean circumferential strain (-8 ± 2% to -7 ± 1%, P = .02) of the infarcted region deteriorated, with no significant change in dyssynchrony (42 ± 12 vs 46 ± 13 m sec, P = .60) in the saline group during the same time period. Change in LVEF was correlated with change in circumferential strain (r = -0.8, P = .002) and dyssynchrony (r = 0.6, P = .02) of the infarct/peri-infarct region at 4 weeks after MI.
  
  
  CONCLUSIONS
  CDC therapy enhanced LVEF by improving circumferential strain and decreasing dyssynchrony of the infarct/peri-infarct region at 4 weeks, but not 1 week, after MI. Cellular resynchronization therapy using CDCs may be an alternative to traditional electrical cellular resynchronization therapy in post-MI dyssynchrony.
authors.affiliation: Johns Hopkins University, 720 Rutland Avenue, Baltimore, MD 21210, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bonios
authors.forename: Connie Y
authors.initials: CY
authors.lastname: Chang
authors.forename: Aurelio
authors.initials: A
authors.lastname: Pinheiro
authors.forename: Veronica Lea
authors.initials: VL
authors.lastname: Dimaano
authors.forename: Takahiro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Christina
authors.initials: C
authors.lastname: Melexopoulou
authors.forename: Frank
authors.initials: F
authors.lastname: Bengel
authors.forename: John
authors.initials: J
authors.lastname: Terrovitis
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Abraham
authors.forename: M Roselle
authors.initials: MR
authors.lastname: Abraham
mesh_terms: D000418:Albumins; D000818:Animals; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D004195:Disease Models, Animal; D004452:Echocardiography; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology; D011091:Polyesters; D049268:Positron-Emission Tomography; D051381:Rats; D011921:Rats, Inbred WKY; D033581:Stem Cell Transplantation / Q000379:methods*; D046509:Tissue Culture Techniques; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000209:etiology / Q000601:surgery*
chemical_list: D000418:Albumins; C522044:PB-127 compound; D011091:Polyesters