title: MRI study of cryoinjury infarction in pig hearts: i. Effects of intrapericardial delivery of bFGF/VEGF embedded in alginate beads.
abstract: The aim of the study was the testing of sustained intrapericardial delivery of vascular growth factors (GFs) from alginate beads on cryoinjury size and perfusion. In domestic pigs (15-20 kg, n = 21), the left ventricular (LV) anterolateral 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 the 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. Cine and T(1) -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 first-pass and late enhancement kinetics were monitored. After 4-week cryoinjury, following the injection of 5 x 10(6) 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 infarct areas. Epicardial GF-containing beads were encapsulated within the hypointense 3-4-week infarct tissue. This tissue had a 75% higher LV thickening index, a lower distribution volume for GdDTPA (0.44 ± 0.12 vs 0.68 ± 0.05, p = 0.02), and 25% faster first-pass Gd kinetics relative to control infarctions. TTC staining revealed TTC-positive islands in the core of treated infarcts, which showed 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. We conclude that sustained intrapericardial release of bFGF + VEGF from alginate beads attached to the epicardium facilitated vascular growth in the cryoinjured area.
authors.affiliation: University of Manitoba, Winnipeg, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: M L
authors.initials: ML
authors.lastname: Gruwel
authors.forename: P
authors.initials: P
authors.lastname: Dreessen de Gervai
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: O
authors.initials: O
authors.lastname: Jilkina
authors.forename: E
authors.initials: E
authors.lastname: Gussakovsky
authors.forename: V
authors.initials: V
authors.lastname: Kupriyanov
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D003080:Cold Temperature / Q000009:adverse effects*; D016503:Drug Delivery Systems / Q000379:methods*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005453:Fluorescence; D005682:Gadolinium; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000494:pharmacology; D020723:Glucuronic Acid / Q000737:chemistry; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020007:Implants, Experimental; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008863:Microspheres; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D010477:Perfusion; D010496:Pericardium / Q000187:drug effects* / Q000473:pathology; D011180:Postmortem Changes; D012815:Signal Processing, Computer-Assisted; D034421:Sus scrofa; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D013778:Tetrazolium Salts; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C009591:triphenyltetrazolium; D020723:Glucuronic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA