title: Modification of infarct material properties limits adverse ventricular remodeling.
abstract: BACKGROUND
  Infarct expansion after myocardial infarction (MI) is an important phenomenon that initiates and sustains adverse left ventricular (LV) remodeling. We tested the hypothesis that infarct modification by material-induced infarct stiffening and thickening limits infarct expansion and LV remodeling.
  
  
  METHODS
  Anteroapical infarction was induced in 21 sheep. Sheep were randomized to injection of saline (2.6 mL) or tissue filler material (2.6 mL) into the infarct within 3 hours of MI. Animals were monitored for 8 weeks with echocardiography to assess infarct expansion and global LV remodeling. Morphometric measurements were performed of excised hearts to quantify infarct thickness. Regional blood flow was assessed with colored microspheres. Infarct material properties were measured using biaxial tensile testing.
  
  
  RESULTS
  Compared with controls at 8 weeks, treatment animals had less infarct expansion, reduced LV dilatation (LV systolic volumes: 60.8±4.3 vs 80.3±6.9 mL; p<0.05), greater ejection fraction (0.310±0.026 vs 0.276±0.013; p<0.05), thicker infarcts (5.5±0.2 vs 2.2±0.3 mm; p<0.05), and greater infarct blood flow (0.22±0.04 vs 0.11±0.03 mL/min/g; p<0.05). The longitudinal peak strain in the treatment group was less (0.05014±0.0141) than the control group (0.1024±0.0101), indicating increased stiffness of the treated infarcts.
  
  
  CONCLUSIONS
  Durable infarct thickening and stiffening can be achieved by infarct biomaterial injection, resulting in the amelioration of infarct expansion and global LV remodeling. Further material optimization will allow for clinical translation of this novel treatment paradigm.
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Masato
authors.initials: M
authors.lastname: Morita
authors.forename: Chad E
authors.initials: CE
authors.lastname: Eckert
authors.forename: Kanji
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: Mio
authors.initials: M
authors.lastname: Noma
authors.forename: Liam P
authors.initials: LP
authors.lastname: Ryan
authors.forename: Jason A
authors.initials: JA
authors.lastname: Burdick
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Jackson
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Gorman
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sacks
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001696:Biomechanical Phenomena; D003094:Collagen / Q000378:metabolism; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D017886:Durapatite; D004452:Echocardiography; D019560:Echocardiography, Three-Dimensional; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology; D020342:Finite Element Analysis; D006439:Hemodynamics / Q000502:physiology; D007267:Injections; D008863:Microspheres; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D012756:Sheep; D013314:Stress, Mechanical; D013718:Tensile Strength; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D001672:Biocompatible Materials; D003094:Collagen; D017886:Durapatite