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Epicardial shock‐wave therapy improves ventricular function in a porcine model of ischaemic heart disease
Author(s) -
Holfeld Johannes,
Zimpfer Daniel,
AlbrechtSchgoer Karin,
Stojadinovic Alexander,
Paulus Patrick,
Dumfarth Julia,
Thomas Anita,
Lobenwein Daniela,
Tepeköylü Can,
Rosenhek Raphael,
Schaden Wolfgang,
Kirchmair Rudolf,
Aharinejad Seyedhossein,
Grimm Michael
Publication year - 2016
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.1890
Subject(s) - medicine , ejection fraction , cardiology , cardiac function curve , myocardial infarction , angiogenesis , shock (circulatory) , coronary artery disease , heart failure
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 the safety and efficacy of epicardial shock‐wave therapy in a preclinical large animal model and to further evaluate mechanisms of action of this novel therapy. Four weeks after left anterior descending (LAD) artery ligation in pigs, the animals underwent re‐thoracotomy with (shock‐wave group, n = 6) or without (control group, n = 5) epicardial shock waves (300 impulses at 0.38 mJ/mm 2 ) 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 haemodynamic stability during treatment and myocardial damage. Four weeks after LAD ligation, LVEF decreased in both the 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 6 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. Epicardial shock‐wave treatment in a large animal model of ischaemic heart failure exerted a positive effect on LVEF improvement and did not show any adverse effects. Angiogenesis was induced by stimulation of VEGF receptors. Copyright © 2014 John Wiley & Sons, Ltd.