Efficacy of therapeutic angiogenesis by intramyocardial injection of pCK-VEGF165 in pigs.
BACKGROUND
Intramyocardial injection of vascular endothelial growth factor (VEGF) plasmid DNA was studied to demonstrate improvement of regional myocardial function.


METHODS
Twenty-one pigs that had undergone ligation of the left anterior descending coronary artery were randomly allocated to one of two treatments: intramyocardial injection of pCK-VEGF165 (VEGF group) or pCK-Null (control group) into the ischemic border zone. Electrocardiogram-gated single-photon emission computed tomography was performed 30 and 60 days after the coronary ligation. Segmental variables of perfusion and function were automatically quantified using a 20-segment model. In the segmental analysis, 119 segments were selected for analysis (71 segments in the VEGF group; 48 segments in the control group). Histologic analysis was also performed in the myocardial tissue of the ischemic border zone.


RESULTS
At day 30, there were no significant differences in segmental perfusion, wall thickening, and wall motion between the two groups. In the VEGF group, all variables of perfusion, wall thickening, and wall motion were significantly improved at day 60 compared with those at day 30 (p < 0.05), while there were no differences in the control group. At day 60, perfusion (p = 0.018), wall motion (p = 0.004), and wall thickening (p = 0.068) of the VEGF group were improved compared with those of the control group. Histologic analysis showed that microcapillary density was significantly higher in the VEGF group than the control group (p < 0.001).


CONCLUSIONS
Intramyocardial injection of pCK-VEGF165 significantly augmented neoangiogenesis in the ischemic area and improved regional myocardial function as well as myocardial perfusion.
Choi
Jae-Sung
JS
Department of Thoracic and Cardiovascular Surgery, Dongguk University International Hospital, Koyang, Korea.
Kim
Ki-Bong
KB
Han
Woong
W
Kim
Dong Sik
DS
Park
Jin Sik
JS
Lee
Jong Jin
JJ
Lee
Dong Soo
DS
D000818:Animals; D004452:Echocardiography; D022761:Gene Transfer, Horizontal; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic; D010957:Plasmids; D013318:Stroke Volume; D013552:Swine; D015899:Tomography, Emission-Computed, Single-Photon; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A