Epicardial shock-wave therapy improves ventricular function in a porcine model of ischaemic heart disease.
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/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 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.
Department of Cardiac Surgery, Innsbruck Medical University, Austria.
Johannes
J
Holfeld
Department of Cardiac Surgery, Medical University of Vienna, Austria.
Daniel
D
Zimpfer
Department of Internal Medicine I, Innsbruck Medical University, Austria.
Karin
K
Albrecht-Schgoer
Combat Wound Initiative Program, Walter Reed Army Medical Center, Washington, DC, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Alexander
A
Stojadinovic
Clinic of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital Frankfurt, Frankfurt am Main, Germany.
Patrick
P
Paulus
Department of Cardiac Surgery, Innsbruck Medical University, Austria.
Julia
J
Dumfarth
Gender Medicine Unit, Department of Internal Medicine III, Medical University of Vienna, Austria.
Anita
A
Thomas
Department of Cardiac Surgery, Innsbruck Medical University, Austria.
Daniela
D
Lobenwein
Department of Cardiac Surgery, Innsbruck Medical University, Austria.
Can
C
Tepeköylü
Department of Internal Medicine II, Medical University of Vienna, Austria.
Raphael
R
Rosenhek
AUVA Trauma Centre Meidling, Vienna, Austria.
Wolfgang
W
Schaden
Combat Wound Initiative Program, Walter Reed Army Medical Center, Washington, DC, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Rudolf
R
Kirchmair
Department of Cardiac Surgery, Medical University of Vienna, Austria.|Laboratory for Cardiovascular Research, Department of Anatomy and Cell Biology, Medical University of Vienna, Austria.
Seyedhossein
S
Aharinejad
Department of Cardiac Surgery, Innsbruck Medical University, Austria.
Michael
M
Grimm
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D019220:High-Energy Shock Waves; D006801:Humans; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000628:therapy; D018919:Neovascularization, Physiologic; D010496:Pericardium; D013552:Swine; D014464:Ultrasonic Therapy / Q000379:methods*; D016277:Ventricular Function, Left
angiogenesis; endothelial cells; left ventricular ejection fraction; myocardial infarction; shockwave therapy; vascular endothelial growth factor