© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
VEGF administration in chronic myocardial ischemia in pigs
aAngiogenesis Research Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
bCardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
cDepartment of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
dDepartment of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
eLocal Med, Palo Alto, CA, USA
fGenentech, Inc., South San Francisco, CA, USA
* Corresponding author. Tel.: +1 (617) 667 5364; Fax: +1 (617) 972 5201; e-mail: msimons@bidmc.harvard.edu
Objective: Previous investigations have shown the effectiveness of sustained intra- or extravascular administration of vascular endothelial growth factor (VEGF) in chronic myocardial ischemia in improvement of left ventricular function. The present investigations were undertaken in order to evaluate efficacy of a single bolus or local intracoronary delivery. Methods: Yorkshire pigs underwent placement of a left circumflex artery ameroid occluder. Three weeks later the animals were randomized to treatment with VEGF (20 µg) accomplished by local intracoronary delivery system (InfusaSleeveTM, n=10), intracoronary bolus infusion (n=7) or by epicardial implantation of an osmotic delivery system (n=7). An additional group of animals received intracoronary administration of saline and served as a control (n=9). Three weeks after initiation of therapy, the animals were evaluated with regard to myocardial perfusion and global as well as regional ventricular function. Results: All three VEGF treatment groups but not the control animals demonstrated a significant increase in the left-to-left (but not right-to-left) collateral index, myocardial blood flow (pre-therapy LCX vs. LAD (average of all groups): 0.76±0.35 vs. 0.96±0.38 ml*min–1*g–1, p=0.03; post-therapy: LCX vs. LAD: 1.16±0.39 vs. 1.15±0.28 ml*min–1*g–1, p=NS) and coronary vasodilatory reserve 3 weeks after growth factor administration. The observed increase in VEGF-induced perfusion correlated with improvement in regional ventricular function in all VEGF-treated groups (pre-therapy vs. post-therapy: i.c. VEGF 20±5.1 vs. 33±4.8; local VEGF 16±2.8 vs. 33.6; pump VEGF 17±3.8 vs. 34±4.9 p<0.05 for all) but not control animals (21±3.3 vs. 27±5.8, p=NS). Conclusion: Single intracoronary delivery (intravascular bolus or local delivery) of VEGF is effective in stimulating physiologically significant angiogenesis in porcine model of chronic myocardial ischemia.
KEYWORDS Angiogenesis; VEGF; Myocardial ischemia; Growth factors; Magnetic Resonance Imaging
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