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


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.
Hendel
R C
RC
Northwestern University Medical School, Chicago, IL, USA. rhendel@rush.edu
Henry
T D
TD
Rocha-Singh
K
K
Isner
J M
JM
Kereiakes
D J
DJ
Giordano
F J
FJ
Simons
M
M
Bonow
R O
RO
D002316:Cardiotonic Agents; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D004176:Dipyridamole; D004280:Dobutamine; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000627:therapeutic use; D005080:Exercise Test; D006801:Humans; D007269:Injections, Intra-Arterial; D008222:Lymphokines / Q000008:administration & dosage* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D015899:Tomography, Emission-Computed, Single-Photon; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014665:Vasodilator Agents
D002316:Cardiotonic Agents; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014665:Vasodilator Agents; D004280:Dobutamine; D004176:Dipyridamole