Extracorporeal Shockwave Therapy Reverses Ischemia- Related Left Ventricular Dysfunction and Remodeling: Molecular-Cellular and Functional Assessment

Extracorporeal Shockwave Therapy Reverses Ischemia- Related Left Ventricular Dysfunction and Remodeling: Molecular-Cellular and Functional Assessment
Jiunn-Jye Sheu (1), Chin-Jen Wang (2)

Institution:
(1) Dept. of Surgery, (2) Dept. of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan

Device and producing company:
none

Introduction:
An optimal treatment for patients with diffuse obstructive arterial disease unsuitable for catheter-based or surgical intervention is still pending. This study tested the hypothesis that extracorporeal shock wave (ECSW) therapy may be a therapeutic alternative under such clinical situation.

Methods:
Myocardial ischemia was induced in male mini-pigs through applying an ameroid constrictor over mid-left anterior descending artery (LAD). Twelve mini-pigs were equally randomized into group 1 (Constrictor over LAD only) and group 2 [Constrictor over LAD plus ECSW (800 impulses at 0.09 mJ/mm2) once 3 months after the procedure].

Results:
Results showed that the parameters measured by echocardiography did not differ between two groups on days 0 and 90. However, echocardiography and left ventricular (LV) angiography showed higher LV ejection fraction and lower LV end- systolic dimension and volume in group 2 on day 180 (p<0.035). Besides, mRNA and protein expressions of CXCR4 and SDF-1α were increased in group 2 (p<0.04). Immunofluorescence staining also showed higher number of vWF-, CD31-, SDF-1α, and CXCR4-positive cells in group 2 (all p<0.04). Moreover, immunohistochemical staining showed notably higher vessel density but lower mean fibrosis area, number of CD40- positive cells and apoptotic nuclei in group 2 (all p<0.045). Mitochondrial protein expression of oxidative stress was lower, whereas cytochrome-C was higher in group 2 (all p<0.03). Furthermore, mRNA expressions of MMP-9, Bax and caspase-3 were lower, whereas Bcl-2, eNOS, VEGF and PGC-1α were higher in group 2 (all p<0.01).

Discussion:
none

Conclusion:
In conclusion, ECSW therapy effectively reversed ischemia-elicited LV dysfunction and remodeling through enhancing angiogenesis and attenuating inflammation and oxidative stress.