Abstract 12363: Epicardial Implantation of Alginate Beads Containing basic Fibroblast + Vascular Endothelium Growth Factors Enhanced Perfusion of Cryoinjury Infarct in Pig Hearts
Purpose: To test whether sustained intrapericardial delivery of vascular growth factors (GFs) from alginate beads affects cryoinjury size and perfusion.
Background: Restoration of the vascular network is an important step in cardiac injury repair, for which vascular GFs were applied systemically or locally. To prolong their action, incorporation in a biopolymer matrix was used.
Methods: In domestic pigs (15–20 kg, n=21) the left ventricular (LV) anterior wall of exposed hearts was cryoinjured using an aluminum rod (25 mm o.d.) cooled in liquid nitrogen. Alginate beads (d=3.2±0.2 mm) containing human recombinant basic fibroblast GF (bFGF, 50 μg) and vascular endothelial GF (VEGF, 50 μg) + heparin (50 μg) or heparin alone (Con, n=5) were sutured to cryoinjured epicardium (GF, n=5; Con, n=3) or pericardium (GF, n=3; Con, n=2) or no beads were implanted (n=4). Four pigs were sham-operated (no beads). Following pericardium and chest closing T1-weighted MRI was performed in vivo at ∼2.5 h and 1, 2, 3 and 4 weeks after injury in a 3T imager. A double bolus of GdDTPA was injected (0.05 and 0.15 mmol/kg) and 1st pass and late enhancement kinetics were acquired. After 4-week cryoinjury, following the injection of 5×106 15-μm NIR fluorescent microspheres (FMS, 645/680 nm), hearts were sliced and examined with fluorescence imaging. Triphenyltetrazolium chloride (TTC) staining was used to determine necrotic areas.
Results: Epicardial GF-containing beads were encapsulated within the hypointense 3–4-week infarct tissue, due to build-up of connective tissue measured as an increase in relative infarct size (84±6 vs. 50±8% in control, p=0.0005). This tissue had a lower distribution volume for GdDTPA relative to control infarctions (0.44±0.12 vs. 0.68±0.05) and 25% faster 1st pass Gd kinetics. TTC staining revealed TTC-positive islands in the core of treated infarcts, which had higher FMS fluorescence relative to surrounding infarct tissue (0.64±0.14 vs. 0.31±0.14; p <0.0001) and to control infarcts (0.37±0.09, p <0.05). GF-beads attached to the pericardium were not effective.
Conclusions: Sustained intrapericardial release of bFGF + VEGF from alginate beads attached to the epicardium facilitated vascular growth in the cryoinjured area without reducing infarct size.
- © 2010 by American Heart Association, Inc.