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.