Sustained epicardial delivery of bFGF and VEGF from alginate beads reduced the distribution volume for GdDTPA (0.44 vs 0.68, p=0.02) and facilitated vascular growth in cryoinjured pig hearts.
Does intrapericardial delivery of bFGF and VEGF embedded in alginate beads improve perfusion and reduce injury size in a pig model of myocardial cryoinjury?
Sustained intrapericardial release of bFGF and VEGF from alginate beads attached to the epicardium facilitated vascular growth and improved perfusion in a pig model of myocardial cryoinjury.
Tasa de eventos absoluta: 0.44% vs 0.68%
valor p: p=0.02
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.
Yang et al. (Fri,) conducted a other in Cryoinjury infarction (n=21). bFGF and VEGF embedded in alginate beads vs. Heparin alone or no beads was evaluated on Distribution volume for GdDTPA (p=0.02). Sustained epicardial delivery of bFGF and VEGF from alginate beads reduced the distribution volume for GdDTPA (0.44 vs 0.68, p=0.02) and facilitated vascular growth in cryoinjured pig hearts.