Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion: Evidence for a dose-dependent effect

Robert Hendel, Timothy D. Henry, Krishna Rocha-Singh, Jeffrey M. Isner, Dean J. Kereiakes, Frank J. Giordano, Michael Simons, Robert O. Bonow

Research output: Contribution to journalArticle

261 Citations (Scopus)

Abstract

Background - Animal models of therapeutic angiogenesis have stimulated development of clinical application in patients with limited options for coronary revascularization. The impact of recombinant human vascular endothelial growth factor (rhVEGF) on myocardial perfusion in humans has not been reported. Methods and Results - Fourteen patients underwent exercise (n = 11), dobutamine (n = 2), or dipyridamole (n = 1) myocardial perfusion single photon emission CT (SPECT) before as well as 30 and 60 days after rhVEGF administration. After uniform processing and display, 2 observers blinded to the timing of the study and dose of rhVEGF reviewed the SPECT images. By a visual, semiquantitative 20-segment scoring method, summed stress scores (SSS) and summed rest scores (SRS) were generated. Although the SSS did not change from baseline to 30 days (21.6 versus 21.5; P = NS), the SRS improved after rhVEGF (13.2 versus 10.4; P < 0.05). Stress and rest perfusion improved in >2 segments infrequently in patients treated with low- dose rhVEGF. However, 5 of 6 patients had improvement in >2 segments at rest and stress with the higher rhVEGF doses. Furthermore, although neither the SSS nor the SRS changed in patients treated with the low doses, the SRS decreased in the high-dose rhVEGF patients at 60 days (14.7 versus 10.7; P < 0.05). Quantitative analysis was consistent with the visual findings but failed to demonstrate statistical significance. Conclusions - Although not designed to demonstrate rhVEGF efficacy, these phase 1 data support the concept that rhVEGF improves myocardial perfusion at rest and provide evidence of a dose-dependent effect.

Original languageEnglish
Pages (from-to)118-121
Number of pages4
JournalCirculation
Volume101
Issue number2
StatePublished - Jan 18 2000
Externally publishedYes

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Perfusion
Photons
human VEGFA protein
Dobutamine
Dipyridamole
Research Design
Animal Models
Exercise

Keywords

  • Angiogenesis
  • Growth substances
  • Tomography

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Hendel, R., Henry, T. D., Rocha-Singh, K., Isner, J. M., Kereiakes, D. J., Giordano, F. J., ... Bonow, R. O. (2000). Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion: Evidence for a dose-dependent effect. Circulation, 101(2), 118-121.

Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion : Evidence for a dose-dependent effect. / Hendel, Robert; Henry, Timothy D.; Rocha-Singh, Krishna; Isner, Jeffrey M.; Kereiakes, Dean J.; Giordano, Frank J.; Simons, Michael; Bonow, Robert O.

In: Circulation, Vol. 101, No. 2, 18.01.2000, p. 118-121.

Research output: Contribution to journalArticle

Hendel, R, Henry, TD, Rocha-Singh, K, Isner, JM, Kereiakes, DJ, Giordano, FJ, Simons, M & Bonow, RO 2000, 'Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion: Evidence for a dose-dependent effect', Circulation, vol. 101, no. 2, pp. 118-121.
Hendel R, Henry TD, Rocha-Singh K, Isner JM, Kereiakes DJ, Giordano FJ et al. Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion: Evidence for a dose-dependent effect. Circulation. 2000 Jan 18;101(2):118-121.
Hendel, Robert ; Henry, Timothy D. ; Rocha-Singh, Krishna ; Isner, Jeffrey M. ; Kereiakes, Dean J. ; Giordano, Frank J. ; Simons, Michael ; Bonow, Robert O. / Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion : Evidence for a dose-dependent effect. In: Circulation. 2000 ; Vol. 101, No. 2. pp. 118-121.
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abstract = "Background - Animal models of therapeutic angiogenesis have stimulated development of clinical application in patients with limited options for coronary revascularization. The impact of recombinant human vascular endothelial growth factor (rhVEGF) on myocardial perfusion in humans has not been reported. Methods and Results - Fourteen patients underwent exercise (n = 11), dobutamine (n = 2), or dipyridamole (n = 1) myocardial perfusion single photon emission CT (SPECT) before as well as 30 and 60 days after rhVEGF administration. After uniform processing and display, 2 observers blinded to the timing of the study and dose of rhVEGF reviewed the SPECT images. By a visual, semiquantitative 20-segment scoring method, summed stress scores (SSS) and summed rest scores (SRS) were generated. Although the SSS did not change from baseline to 30 days (21.6 versus 21.5; P = NS), the SRS improved after rhVEGF (13.2 versus 10.4; P < 0.05). Stress and rest perfusion improved in >2 segments infrequently in patients treated with low- dose rhVEGF. However, 5 of 6 patients had improvement in >2 segments at rest and stress with the higher rhVEGF doses. Furthermore, although neither the SSS nor the SRS changed in patients treated with the low doses, the SRS decreased in the high-dose rhVEGF patients at 60 days (14.7 versus 10.7; P < 0.05). Quantitative analysis was consistent with the visual findings but failed to demonstrate statistical significance. Conclusions - Although not designed to demonstrate rhVEGF efficacy, these phase 1 data support the concept that rhVEGF improves myocardial perfusion at rest and provide evidence of a dose-dependent effect.",
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AU - Isner, Jeffrey M.

AU - Kereiakes, Dean J.

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N2 - Background - Animal models of therapeutic angiogenesis have stimulated development of clinical application in patients with limited options for coronary revascularization. The impact of recombinant human vascular endothelial growth factor (rhVEGF) on myocardial perfusion in humans has not been reported. Methods and Results - Fourteen patients underwent exercise (n = 11), dobutamine (n = 2), or dipyridamole (n = 1) myocardial perfusion single photon emission CT (SPECT) before as well as 30 and 60 days after rhVEGF administration. After uniform processing and display, 2 observers blinded to the timing of the study and dose of rhVEGF reviewed the SPECT images. By a visual, semiquantitative 20-segment scoring method, summed stress scores (SSS) and summed rest scores (SRS) were generated. Although the SSS did not change from baseline to 30 days (21.6 versus 21.5; P = NS), the SRS improved after rhVEGF (13.2 versus 10.4; P < 0.05). Stress and rest perfusion improved in >2 segments infrequently in patients treated with low- dose rhVEGF. However, 5 of 6 patients had improvement in >2 segments at rest and stress with the higher rhVEGF doses. Furthermore, although neither the SSS nor the SRS changed in patients treated with the low doses, the SRS decreased in the high-dose rhVEGF patients at 60 days (14.7 versus 10.7; P < 0.05). Quantitative analysis was consistent with the visual findings but failed to demonstrate statistical significance. Conclusions - Although not designed to demonstrate rhVEGF efficacy, these phase 1 data support the concept that rhVEGF improves myocardial perfusion at rest and provide evidence of a dose-dependent effect.

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