Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo.
BACKGROUND
Prognosis of ischemic cardiomyopathy still remains poor because of the lack of effective treatments. To develop a noninvasive therapy for the disorder, we examined the in vitro and vivo effects of extracorporeal shock wave (SW) that could enhance angiogenesis.


RESULTS
SW treatment applied to cultured human umbilical vein endothelial cells significantly upregulated mRNA expression of vascular endothelial growth factor and its receptor Flt-1 in vitro. A porcine model of chronic myocardial ischemia was made by placing an ameroid constrictor at the proximal segment of the left circumflex coronary artery, which gradually induced a total occlusion of the artery with sustained myocardial dysfunction but without myocardial infarction in 4 weeks. Thereafter, extracorporeal SW therapy to the ischemic myocardial region (200 shots/spot for 9 spots at 0.09 mJ/mm2) was performed (n=8), which induced a complete recovery of left ventricular ejection fraction (51+/-2% to 62+/-2%), wall thickening fraction (13+/-3% to 30+/-3%), and regional myocardial blood flow (1.0+/-0.2 to 1.4+/-0.3 mL x min(-1) x g(-1)) of the ischemic region in 4 weeks (all P<0.01). By contrast, animals that did not receive the therapy (n=8) had sustained myocardial dysfunction (left ventricular ejection fraction, 48+/-3% to 48+/-1%; wall thickening fraction, 13+/-2% to 9+/-2%) and regional myocardial blood flow (1.0+/-0.3 to 0.6+/-0.1 mL x min(-1) x g(-1)). Neither arrhythmias nor other complications were observed during or after the treatment. SW treatment of the ischemic myocardium significantly upregulated vascular endothelial growth factor expression in vivo.


CONCLUSIONS
These results suggest that extracorporeal cardiac SW therapy is an effective and noninvasive therapeutic strategy for ischemic heart disease.
Nishida
Takahiro
T
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Shimokawa
Hiroaki
H
Oi
Keiji
K
Tatewaki
Hideki
H
Uwatoku
Toyokazu
T
Abe
Kohtaro
K
Matsumoto
Yasuharu
Y
Kajihara
Noriyoshi
N
Eto
Masataka
M
Matsuda
Takehisa
T
Yasui
Hisataka
H
Takeshita
Akira
A
Sunagawa
Kenji
K
D000818:Animals; D002478:Cells, Cultured / Q000378:metabolism; D003097:Collateral Circulation; D003326:Coronary Circulation; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D019220:High-Energy Shock Waves / Q000627:therapeutic use*; D006801:Humans; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034421:Sus scrofa; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1
D011506:Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1