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摘要
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 (25mm o.d.) cooled in liquid nitrogen. Alginate beads (d=3.2 +/- 0.2mm), containing human recombinant basic fibroblast GF (bFGF, 50 mu g) and vascular endothelial GF (VEGF, 50 mu g)+heparin (50 mu g) 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 T1-weighted MRI was performed in vivo at similar to 2.5h and 1, 2, 3 and 4weeks after injury in a 3T imager. A double bolus of GdDTPA was injected (0.05 and 0.15mmol/kg) and first-pass and late enhancement kinetics were monitored. After 4-week cryoinjury, following the injection of 5x106 15-mu m NIR fluorescent microspheres (FMS, 645/680nm), 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 %26lt; 0.0001) and to control infarcts (0.37 +/- 0.09, p %26lt; 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.
- 出版日期2012-1
