title: Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nishida
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Oi
authors.forename: Hideki
authors.initials: H
authors.lastname: Tatewaki
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Uwatoku
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Abe
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Kajihara
authors.forename: Masataka
authors.initials: M
authors.lastname: Eto
authors.forename: Takehisa
authors.initials: T
authors.lastname: Matsuda
authors.forename: Hisataka
authors.initials: H
authors.lastname: Yasui
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: 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
chemical_list: D011506:Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1