Background: Previously we have shown that epicardial shock wave therapy improves left ventricular ejection fraction (LVEF) in a rat model of myocardial infarction.
In the present experiments we aimed to address safety and efficacy of epicardial shock wave therapy in a preclinical large animal model and to further evaluate mechanism of action of this novel therapy.
Methods: Four weeks after left anterior descending (LAD) artery ligation in pigs, animals underwent re-thoracotomy with (shock wave group, n=6) or without (control group, n=5) epicardial shock waves (300 impulses at 0.38mJ/mm²) applied to the infarcted anterior wall. Efficacy endpoints were improvement of LVEF and induction of angiogenesis 6 weeks after shock wave therapy. Safety endpoints were hemodynamic stability during treatment and myocardial damage.
Results: Four weeks after LAD ligation, LVEF decreased in both shock wave (43±3%, p<0.001) and control (41±4%, p=0.012) groups. LVEF markedly improved in shock wave animals 6 weeks after treatment (62±9%, p=0.006), no improvement was observed in controls (41±4%, p=0.36) yielding a significant difference. Quantitative histology revealed significant angiogenesis six weeks after treatment (controls 2±0.4 arterioles/high power field vs. treatment group 9±3, p=0.004). No acute or chronic adverse effects were observed. As a potential mechanism of action in-vitro experiments showed stimulation of VEGF receptors after shock wave treatment in human coronary artery endothelial cells.
Conclusions: Epicardial shock wave treatment in a large animal model of ischemic heart failure exerted positive effect on LVEF improvement and did not show any adverse effects. Angiogenesis was induced by stimulation of VEGF receptors.
