Published Online
on November 1, 2004

A more recent version of this article appeared on November 9, 2004

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Submitted on May 5, 2003
Revised on June 2, 2004
Accepted on June 17, 2004

Extracorporeal Cardiac Shock Wave Therapy Markedly Ameliorates Ischemia-Induced Myocardial Dysfunction in Pigs in Vivo

Takahiro Nishida MD, Hiroaki Shimokawa MD^*, Keiji Oi MD, Hideki Tatewaki MD, Toyokazu Uwatoku MD, Kohtaro Abe MD, Yasuharu Matsumoto MD, Noriyoshi Kajihara MD, Masataka Eto MD, Takehisa Matsuda PhD, Hisataka Yasui MD, Akira Takeshita MD, and Kenji Sunagawa MD

From the Departments of Cardiovascular Surgery (T.N., H.T., N.K., M.E., H.Y.), Cardiovascular Medicine (K.O., H.S., T.U., K.A., Y.M., A.T., K.S.), and Biomedical Engineering (T.M.), and the 21st Century COE Program on Lifestyle-Related Diseases (H.S., T.M.), Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

^* To whom correspondence should be addressed. E-mail: shimo{at}cardiol.med.kyushu-u.ac.jp.

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.

Methods and 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 · min^-1 · 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 · min^-1 · 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.

Key words: angiogenesis • contractility • hibernation • ischemia • regional blood flow

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