Angiogenic effects of long-term enhanced external counterpulsation in a dog model of myocardial infarction.
Enhanced external counterpulsation (EECP) is an effective noninvasive treatment of coronary artery disease. Its mechanism of action remains unknown. An acute coronary occlusion dog model was created to explore the angiogenic effect of EECP. After coronary occlusion, 12 dogs were randomly assigned to either EECP (n = 6) or control (n = 6). Immunohistochemical studies of alpha-actin and von Willebrand factor (vWF) were used to detect newly developed microvessels. Systemic and local vascular endothelial growth factor (VEGF) were identified by ELISA and reverse transcriptase PCR analysis. There was a significant increase in the density of microvessels per squared millimeter in the infarcted regions of the EECP group compared with the control group (vWF, 15.2 +/- 6.3 vs. 4.9 +/- 2.1, P < 0.05; alpha-actin, 11.8 +/- 5.3 vs. 3.4 +/- 1.2, P < 0.05). The positive-stained area per squared micrometer also increased significantly (alpha-actin, 6.6 x 10(3) +/- 2.9 x 10(3) microm2 vs. 0.6 x 10(3) +/- 0.5 x 10(3) microm2, P < 0.05; vWF, 5.7 x 10(3) +/- 1.9 x 10(3) microm2 vs. 1.7 x 10(3) +/- 1.4 x 10(3) microm2, P < 0.05). Immunohistochemical staining and reverse transcriptase PCR analysis documented a significant increase in VEGF expression. These factors associated with angiogenesis corresponded to improved myocardial perfusion by 99mTc-sestamibi single-photon emission computed tomography. Angiogenesis may be a mechanism of action for the improved myocardial perfusion demonstrated after EECP therapy.
Wu
Guifu
G
Cardiology and the Key Lab on Assisted Circulation of the Health Ministry of China, The First Affiliated Hospital/Sun Yat-sen University, Guangzhou, People's Republic of China.
Du
Zhimin
Z
Hu
Chenghen
C
Zheng
Zhensheng
Z
Zhan
Chengyang
C
Ma
Hong
H
Fang
Dianqiu
D
Ahmed
Khan Tanveer
KT
Laham
Roger J
RJ
Hui
John C K
JC
Lawson
William E
WE
D000818:Animals; D003331:Coronary Vessels / Q000473:pathology; D015908:Counterpulsation; D004195:Disease Models, Animal; D004285:Dogs; D015870:Gene Expression; D006439:Hemodynamics; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D042461:Vascular Endothelial Growth Factor A