title: Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in Swine.
abstract: OBJECTIVE
  This study sought to determine whether alginate biomaterial can be delivered effectively into the infarcted myocardium by intracoronary injection to prevent left ventricular (LV) remodeling early after myocardial infarction (MI).
  
  
  BACKGROUND
  Although injectable biomaterials can improve infarct healing and repair, the feasibility and effectiveness of intracoronary injection have not been studied.
  
  
  METHODS
  We prepared a calcium cross-linked alginate solution that undergoes liquid to gel phase transition after deposition in infarcted myocardium. Anterior MI was induced in swine by transient balloon occlusion of left anterior descending coronary artery. At 4 days after MI, either alginate solution (2 or 4 ml) or saline was injected selectively into the infarct-related coronary artery. An additional group (n = 19) was treated with incremental volumes of biomaterial (1, 2, and 4 ml) or 2 ml saline and underwent serial echocardiography studies.
  
  
  RESULTS
  Examination of hearts harvested after injection showed that the alginate crossed the infarcted leaky vessels and was deposited as hydrogel in the infarcted tissue. At 60 days, control swine experienced an increase in left ventricular (LV) diastolic area by 44%, LV systolic area by 45%, and LV mass by 35%. In contrast, intracoronary injection of alginate (2 and 4 ml) prevented and even reversed LV enlargement (p < 0.01). Post-mortem analysis showed that the biomaterial (2 ml) increased scar thickness by 53% compared with control (2.9 +/- 0.1 mm vs. 1.9 +/- 0.3 mm; p < 0.01) and was replaced by myofibroblasts and collagen.
  
  
  CONCLUSIONS
  Intracoronary injection of alginate biomaterial is feasible, safe, and effective. Our findings suggest a new percutaneous intervention to improve infarct repair and prevent adverse remodeling after reperfused MI.
authors.affiliation: Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Aviv University, Tel-Hashomer 52621, Israel. leorj@post.tau.ac.il
authors.forename: Jonathan
authors.initials: J
authors.lastname: Leor
authors.forename: Shmuel
authors.initials: S
authors.lastname: Tuvia
authors.forename: Victor
authors.initials: V
authors.lastname: Guetta
authors.forename: Ferenc
authors.initials: F
authors.lastname: Manczur
authors.forename: David
authors.initials: D
authors.lastname: Castel
authors.forename: Udi
authors.initials: U
authors.lastname: Willenz
authors.forename: Ors
authors.initials: O
authors.lastname: Petneházy
authors.forename: Natali
authors.initials: N
authors.lastname: Landa
authors.forename: Micha S
authors.initials: MS
authors.lastname: Feinberg
authors.forename: Eli
authors.initials: E
authors.lastname: Konen
authors.forename: Orly
authors.initials: O
authors.lastname: Goitein
authors.forename: Orna
authors.initials: O
authors.lastname: Tsur-Gang
authors.forename: Mazal
authors.initials: M
authors.lastname: Shaul
authors.forename: Lea
authors.initials: L
authors.lastname: Klapper
authors.forename: Smadar
authors.initials: S
authors.lastname: Cohen
mesh_terms: D000464:Alginates / Q000008:administration & dosage*; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D020723:Glucuronic Acid / Q000008:administration & dosage; D006339:Heart Rate; D006603:Hexuronic Acids / Q000008:administration & dosage; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage*; D015552:Injections, Intralesional; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D013318:Stroke Volume; D013552:Swine; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid