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. 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/mm(2)) 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.