title: Effect of catheter-based transendocardial delivery of stromal cell-derived factor 1alpha on left ventricular function and perfusion in a porcine model of myocardial infarction.
abstract: BACKGROUND
  Myocardial regeneration after myocardial infarction can occur via stem cell recruitment. Stromal cell-derived factor 1alpha (SDF-1alpha) has been shown to be critical for stem cell homing to injured tissue.
  
  
  METHODS
  Myocardial infarction was induced in pigs via microembolization of the distal left anterior descending artery. Two weeks after myocardial infarction animals underwent catheter-based transendocardial injection of SDF-1alpha into the periinfarct myocardium (18 injections, 5 ìg per injection) (n = 12) or sham-intervention (n = 8). Tc99m sestamibi single-photon emission computed tomography (SPECT) and electromechanical mapping (EMM) of the left ventricle were performed two and seven weeks after myocardial infarction.
  
  
  RESULTS
  Infarct size by tetrazolium staining was similar in both groups (8.9 +/-1.2% of left ventricle vs. 8.9 +/- 2.6%). Vessel density in the periinfarct area was significantly higher in SDF-1alpha treated animals than in controls (349 +/- 17/mm2 vs. 276 +/- 21/mm2, p < 0.05). Myocardial perfusion (SPECT) did not change in either group. Ejection fraction and stroke volume (EMM) decreased in SDF-1alpha animals and increased in controls (difference between groups p = 0.05 for ejection fraction and p < 0.05 for stroke volume). Linear local shortening (EMM) did not change in controls (11.4 +/- 1.3% to 11.5 +/- 0.5%) but decreased significantly in SDF-1alpha treated animals (12.1 +/- 0.9% to 8.4 +/- 0.9%, p < 0.05, p < 0.05 for difference between groups). SDF-1 delivery was associated with a substantial loss of collagen in the periinfarct area (32+/-5% vs. 61+/-6% in control animals, p < 0.005).
  
  
  CONCLUSIONS
  A strategy to augment stem cell homing by catheter-based transendocardial delivery of SDF-1alpha in experimental myocardial infarction increases periinfarct vessel density, fails to improve myocardial perfusion, is associated with loss of collagen in the periinfarct area and impairs left ventricular function.
authors.affiliation: Department of Cardiology, RWTH Aachen University, Pauwelstrasse 30, 52074 Aachen, Germany. kckoch@ukaachen.de
authors.forename: Karl-Christian
authors.initials: KC
authors.lastname: Koch
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Schaefer
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Liehn
authors.forename: Christos
authors.initials: C
authors.lastname: Rammos
authors.forename: Dominik
authors.initials: D
authors.lastname: Mueller
authors.forename: Joerg
authors.initials: J
authors.lastname: Schroeder
authors.forename: Tarek
authors.initials: T
authors.lastname: Dimassi
authors.forename: Thaddaeus
authors.initials: T
authors.lastname: Stopinski
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
mesh_terms: D000818:Animals; D002406:Catheterization, Peripheral; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000008:administration & dosage*; D003094:Collagen; D003331:Coronary Vessels / Q000187:drug effects; D005260:Female; D007261:Infusions, Intra-Arterial; D036502:Infusions, Intralesional; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D003094:Collagen