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/m²). 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.

Abbreviations and Acronyms: BNP, brain natriuretic peptide, Flt-1, Fms-related tyrosine kinase 1, LAD, left anterior descending artery, LV, left ventricular, PCR, polymerase chain reaction, PlGF, placental growth factor, SWT, shock wave therapy, VEGF, vascular endothelial growth factor, vWF, von Willebrand factor

CTSNet classification: 23, 29, 30