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 develo pment of clinical application in patients with limited options for coronary revascularization. The impact of recombinant human vascular endothelial gr owth factor (rhVEGF) on myocardial perfusion in humans has not been reporte d. Methods and Results-Fourteen patients underwent exercise (n=11), dobutamine (n=2), or dipyridamole (n=1) myocardial perfusion single photon emission C T (SPECT) before as well as 30 and 60 days after rhVEGF administration. Aft er uniform processing and display, 2 observers blinded to the timing of the study and dose of rhVEGF reviewed the SPECT images. By a visual, semiquant itative 20-segment scoring method, summed stress scores (SSS) and summed re st scores (SRS) were generated. Although the SSS did not change from baseli ne 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 in frequently in patients treated with low-dose rhVEGF, However, 5 of 6 patien ts had improvement in >2 segments at rest and stress with the higher rhVEGF doses. Furthermore, although neither the SSS nor the SRS changed in patien ts treated with the low doses, the SRS decreased in the high-dose rhVEGF pa tients at 60 days (14.7 versus 10.7; P<0.05). Quantitative analysis was con sistent with the visual findings but failed to demonstrate statistical sign ificance. Conclusions-Although not designed to demonstrate rhVEGF efficacy, these pha se 1 data support the concept that rhVEGF improves myocardial perfusion at rest and provide evidence of a dose-dependent effect.