title: Injectable microsphere gel progressively improves global ventricular function, regional contractile strain, and mitral regurgitation after myocardial infarction.
abstract: BACKGROUND
  There is continued need for therapies which reverse or abate the remodeling process after myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model.
  
  
  METHODS
  Twenty-five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into the following 4 groups: 1-week treatment; 1-week control; 4-week treatment; and 4-week control. After infarction, animals received either twenty 150 μL calcium hydroxyapatite gel or saline injections within the infarct. At their respective time points, echocardiograms, cardiac magnetic resonance imaging, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content.
  
  
  RESULTS
  Global and regional left ventricular functions were depressed in all infarcted subjects at 1 week compared with healthy controls. By 4-weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared with infarcted controls (ejection fraction 0.485 ± 0.019 vs 0.38 ± 0.017, p < 0.01). Similarly, regional borderzone radial contractile strain (16.3% ± 1.5% vs 11.2% ± 1.5%, p = 0.04), MR grade (0.4 ± 0.2 vs 1.2 ± 0.2, p = 0.04), and infarct thickness (7.8 ± 0.5 mm vs 4.5 ± 0.2 mm, p < 0.01) were improved at this time point in the treatment group compared with infarct controls.
  
  
  CONCLUSIONS
  Calcium hydroxyapatite injection after MI progressively improves global left ventricular function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is a viable alternative in the current management of heart failure.
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: McGarvey
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Walter R T
authors.initials: WR
authors.lastname: Witschey
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Manabu
authors.initials: M
authors.lastname: Takebe
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Aoki
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Burdick
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina.
authors.forename: Francis G
authors.initials: FG
authors.lastname: Spinale
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Gorman
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: James J
authors.initials: JJ
authors.lastname: Pilla
authors.affiliation: Gorman Cardiovascular Research Group, Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: robert.gorman@uphs.upenn.edu.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage*; D017886:Durapatite / Q000008:administration & dosage*; D005782:Gels / Q000008:administration & dosage*; D015552:Injections, Intralesional; D008297:Male; D008863:Microspheres; D008944:Mitral Valve Insufficiency / Q000209:etiology / Q000628:therapy*; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000628:therapy*; D020127:Recovery of Function; D013552:Swine; D016276:Ventricular Function
chemical_list: D001672:Biocompatible Materials; D005782:Gels; D017886:Durapatite