title: Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties.
abstract: Direct intramyocardial injection of mesenchymal stem cells (MSCs) improves left ventricular ejection fraction (LVEF) and may increase ventricular arrhythmia in hearts with myocardial infarction (MI). We hypothesized that intravenous MSCs given early after acute MI would engraft in injured myocardium, improve LV function, and result in pro-arrhythmic electrical remodeling. We created an apical infarction in swine by balloon occlusion/reperfusion, administered diI-labeled allogeneic bone marrow derived MSCs intravenously 30 min post-reperfusion and measured LVEF and wall thickness at baseline, 1 month, and 3 months. Epicardial effective refractory periods (ERPs) were determined before sacrifice. At 3 months, treated pigs [n=7] had significantly higher LVEF than controls [n=8] (49+/-2% vs. 44+/-3%, P=0.015) and significantly less wall thickening of non-infarcted myocardium. ERPs were significantly shorter than controls at all pacing cycle lengths (P<or=0.002), suggesting a pro-arrhythmic potential. DiI was found in the lungs, in infarct, and peri-infarct myocardium.
  
  
  CONCLUSIONS
  IV infusion of MSCs soon after acute MI in swine improves LVEF and limits wall thickening in the remote non-infarcted myocardium, consistent with a beneficial effect on post-MI ventricular remodeling. Since there is no need for immune suppression or clinical expertise, IV infusion of MSCs may expand the potential clinical application of stem cell therapy.
authors.affiliation: Division of Cardiology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Price
authors.forename: Chung-Chuan
authors.initials: CC
authors.lastname: Chou
authors.forename: Malka
authors.initials: M
authors.lastname: Frantzen
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Saibal
authors.initials: S
authors.lastname: Kar
authors.forename: Steve
authors.initials: S
authors.lastname: Lee
authors.forename: Prediman K
authors.initials: PK
authors.lastname: Shah
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Martin
authors.forename: Michael
authors.initials: M
authors.lastname: Lill
authors.forename: James S
authors.initials: JS
authors.lastname: Forrester
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
authors.forename: Raj R
authors.initials: RR
authors.lastname: Makkar
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D017023:Coronary Angiography; D004195:Disease Models, Animal; D004452:Echocardiography; D004594:Electrophysiology / Q000379:methods; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000473:pathology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy*; D015424:Reperfusion; D013552:Swine; D016277:Ventricular Function, Left / Q000502:physiology*