Direct epicardial shock wave therapy improves ventricular function and induces angiogenesis in ischemic heart failure

Objectives: Direct application of low-energy unfocused shock waves induces angiogenesis in ischemic soft tissue. The potential effects of epicardial shock wave therapy applied in direct contact to ischemic myocardium are uncertain. Methods: For induction of ischemic heart failure in a rodent model, a left anterior descending artery ligation was performed in adult Sprague-Dawley rats. After 4 weeks, reoperation with (treatment group, n = 60) or without (control group, n = 60) epicardial shock wave therapy was performed. Low-energy shock waves were applied in direct contact with the infarcted myocardium (300 impulses at 0.38 mJ/m(2)). Additionally, healthy animals (n = 30) with normal myocardium were studied. Angiogenesis, ventricular function upregulation of growth factors, and brain natriuretic peptide levels were analyzed. Results: Histologic analysis revealed significant angiogenesis 6 weeks (treatment group: 8.2 +/- 3.7 vs control group: 2.9 +/- 1.9 vessels per field, P = .016) and 14 weeks ( treatment group: 7.1 +/- 3.1 vs control group: 3.2 +/- 1.8 vessels per field, P = .011) after shock wave treatment. In the treatment group ventricular function improved throughout the follow-up period ( 6 weeks: 37.4% +/- 9% [P <. 001] and 14 weeks: 39.5% +/- 9% [P <. 001]). No improvement of ventricular function was observed in the control group (6 weeks: 28.6% +/- 5% and 14 weeks: 21.4% +/- 5%). Rat brain natriuretic peptide 45 levels were lower in the treatment group compared with those in the control group 6 and 14 weeks after treatment. Vascular endothelial growth factor, Fms-related tyrosine kinase 1, and placental growth factor levels were upregulated after 24 and 48 hours and 7 days in the treatment group. No effects on healthy myocardium were observed. Conclusion: Direct epicardial low-energy shock wave therapy induces angiogenesis and improves ventricular function in a rodent model of ischemic heart failure.