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Efficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia.

Publication ,  Journal Article
Sato, K; Wu, T; Laham, RJ; Johnson, RB; Douglas, P; Li, J; Sellke, FW; Bunting, S; Simons, M; Post, MJ
Published in: J Am Coll Cardiol
February 2001

OBJECTIVES: We sought to optimize vascular endothelial growth factor (VEGF) treatment for therapeutic angiogenesis in myocardial ischemia, we explored the efficacy of five different regimens. BACKGROUND: Although VEGF165 is one of the most potent pro-angiogenic growth factors, VEGF165 treatment for myocardial ischemia has been hampered by low efficacy and dose-limiting hypotension after systemic or intracoronary delivery. METHODS: This study evaluated the effect of intravenous or intracoronary rhVEGF165 in the presence or absence of nitric oxide (NO) synthase inhibition in a porcine model of chronic myocardial ischemia. Forty-two Yorkshire pigs with chronically occluded left circumflex coronary arteries were randomly assigned to receive 10 microg/kg of VEGF165: 1) rapid (40 min) intravenous VEGF165 0.25 microg/kg/min, 2) slow (200 min) intravenous VEGF165 0.05 microg/kg/min, 3) rapid intracoronary VEGF165 0.25 microg/kg/min, 4) rapid intracoronary VEGF165 0.25 microg/kg/min + nitro-L-arginine methyl ester hydrochloride (L-NAME) or 5) rapid vehicle infusion. RESULTS: Intracoronary and intravenous VEGF165 induced hypotension. Intracoronary VEGF-induced hypotension was blocked by L-NAME. Coronary angiography three weeks after treatment showed improvement in collateral index in both intracoronary groups but not the intravenous VEGF165 groups. Likewise, myocardial blood flow and microvascular function in the ischemic territory improved in both intracoronary groups but not in the intravenous groups. Global and regional myocardial function showed no significant improvements in any groups. CONCLUSIONS: Intracoronary infusion of VEGF165 significantly improves blood flow to the ischemic myocardium. Concomitant administration of L-NAME inhibits VEGF-induced hypotension while most likely preserving VEGF-induced angiogenesis. Intravenous infusion of VEGF165 was not effective in augmenting either myocardial flow or function in this model.

Duke Scholars

Published In

J Am Coll Cardiol

DOI

ISSN

0735-1097

Publication Date

February 2001

Volume

37

Issue

2

Start / End Page

616 / 623

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factors
  • Vascular Endothelial Growth Factor A
  • Swine
  • Myocardial Ischemia
  • Myocardial Contraction
  • Microcirculation
  • Male
  • Lymphokines
  • Infusions, Intravenous
  • Infusions, Intra-Arterial
 

Citation

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Sato, K., Wu, T., Laham, R. J., Johnson, R. B., Douglas, P., Li, J., … Post, M. J. (2001). Efficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia. J Am Coll Cardiol, 37(2), 616–623. https://doi.org/10.1016/s0735-1097(00)01144-x
Sato, K., T. Wu, R. J. Laham, R. B. Johnson, P. Douglas, J. Li, F. W. Sellke, S. Bunting, M. Simons, and M. J. Post. “Efficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia.J Am Coll Cardiol 37, no. 2 (February 2001): 616–23. https://doi.org/10.1016/s0735-1097(00)01144-x.
Sato K, Wu T, Laham RJ, Johnson RB, Douglas P, Li J, et al. Efficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia. J Am Coll Cardiol. 2001 Feb;37(2):616–23.
Sato, K., et al. “Efficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia.J Am Coll Cardiol, vol. 37, no. 2, Feb. 2001, pp. 616–23. Pubmed, doi:10.1016/s0735-1097(00)01144-x.
Sato K, Wu T, Laham RJ, Johnson RB, Douglas P, Li J, Sellke FW, Bunting S, Simons M, Post MJ. Efficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia. J Am Coll Cardiol. 2001 Feb;37(2):616–623.
Journal cover image

Published In

J Am Coll Cardiol

DOI

ISSN

0735-1097

Publication Date

February 2001

Volume

37

Issue

2

Start / End Page

616 / 623

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factors
  • Vascular Endothelial Growth Factor A
  • Swine
  • Myocardial Ischemia
  • Myocardial Contraction
  • Microcirculation
  • Male
  • Lymphokines
  • Infusions, Intravenous
  • Infusions, Intra-Arterial