Microvessel angiogenesis: a possible cardioprotective mechanism of external counterpulsation for canine myocardial infarction.
BACKGROUND
Enhanced external counterpulsation (EECP) has been demonstrated to be effective in the treatment of patients with coronary artery disease (CAD). It has been proposed that the beneficial effects of EECP observed in clinical studies may be due to the formation of new blood vessels (angiogenesis) and collateral development. However, there is a relative paucity of basic studies to support the proposed mechanisms.


METHODS
Twelve Beagle dogs were anesthetized with 3% sodium pentobarbital, 1 mg/kg intraperitoneal injection and mechanically ventilated for the development of myocardial infarction. After coronary occlusion, all animals were randomly assigned to either EECP or control. EECP was given one hour per day, 5 days a week, for a total of 28 to 30 hours treatment over a 6-week course. 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 enzyme linked immunosorbent assay (ELISA) and reverse-transcriptional polymerase chain reaction (RT-PCR) analysis.


RESULTS
There was a significant increase in the density of microvessels per mm(2) in the infarcted regions of EECP group compared to control group (vWF, 15.2 +/- 6.3 versus 4.9 +/- 2.1, P < 0.05; alpha-actin, 11.8 +/- 5.3 versus 3.4 +/- 1.2, P < 0.05), along with significant increase of positive vWF and alpha-actin stained area. Both immunohistochemical staining and RT-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.


CONCLUSIONS
Microvessel angiogenesis may be a mechanism of action for the improved myocardial perfusion after EECP therapy.
Wu
Gui-fu
GF
Division of Cardiology, First Affiliated Hospital, Sun Yat-sen University, and the Key Lab on Assisted Circulation of the Health Ministry of China, Guangzhou 511080, China.
Du
Zhi-min
ZM
Hu
Cheng-hen
CH
Zheng
Zhen-sheng
ZS
Zhan
Cheng-yang
CY
Ma
Hong
H
Fang
Dian-qiu
DQ
Hui
John C K
JC
Lawson
William E
WE
D000818:Animals; D015908:Counterpulsation; D004285:Dogs; D006439:Hemodynamics; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics; D016277:Ventricular Function, Left
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A