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Research Papers:

Extracorporeal shock wave treatment attenuated left ventricular dysfunction and remodeling in mini-pig with cardiorenal syndrome

Jiunn-Jye Sheu, Hani E.E. Ali, Ben-Chung Cheng, Hsin-Ju Chiang, Pei-Hsun Sung, Kuan-Hung Chen, Chih-Chao Yang, Yen-Ta Chen, John Y. Chiang, Pao-Yuan Lin, Sarah Chua, Han-Tan Chai, Sheng-Ying Chung, Cheuk-Kwan Sun and Hon-Kan Yip _

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Oncotarget. 2017; 8:54747-54763. https://doi.org/10.18632/oncotarget.18287

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Abstract

Jiunn-Jye Sheu1,*,**, Hani E.E. Ali1,**, Ben-Chung Cheng2, Hsin-Ju Chiang3, Pei-Hsun Sung4, Kuan-Hung Chen5, Chih-Chao Yang2, Yen-Ta Chen6, John Y. Chiang7, Pao-Yuan Lin8, Sarah Chua4, Han-Tan Chai4, Sheng-Ying Chung4, Cheuk-Kwan Sun9 and Hon-Kan Yip4,10,11,12,13,*

1Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

3Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

4Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

5Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

6Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

7Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan

8Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

9Department of Emergency Medicine, E-Da Hospital, I-Shou University School of Medicine for International Students, Kaohsiung, Taiwan

10Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

11Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

12Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

13Department of Nursing, Asia University, Taichung, Taiwan

*Indicates equal contribution in this study as compared with the correspondence author

**Indicates equal contribution in this study as compared with the first author

Correspondence to:

Hon-Kan Yip, email: [email protected]

Keywords: myocardial ischemia, LV remodeling, cardiorenal syndrome, angiogenesis, extracorporeal shock wave

Received: February 17, 2017    Accepted: May 09, 2017    Published: May 30, 2017

ABSTRACT

This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can improve ischemia-induced left ventricular (LV) dysfunction in mini-pig with co-existing chronic kidney disease (CKD). LV ischemia in mini-pigs was induced by applying an ameroid constrictor over mid-left anterior descending artery (LAD), while model of CKD was established by right nephrectomy with partial ligation of left renal arterioles 2 weeks before LAD constriction. Thirty mini-pigs were randomly divided into group 1 (sham-control), group 2 (LV-ischemia), group 3 (LV-ischemia + CKD), Group 4 [LV-ischemia + ECSW (applied 1200 shots at 0.1 mJ/m2/equally to 4-ischemic regions by day-90 after LAD constriction], and group 5 (LV-ischemia-CKD + ECSW). By day-180 after CKD induction, echocardiography showed that LV ejection fraction (LVEF) was highest in group 1, lowest in group 3, significantly lower in group 2 than that in groups 4 and 5, and significantly lower in group 5 than that in group 4, whereas LV-end systolic and diastolic dimensions displayed an opposite pattern (all p<0.001). Protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax), fibrotic (TGF-β/Smad3), pressure/volume-overload (BNP/β-MHC), endothelial (CD31/vWF) and mitochondrial-integrity (PGC-1/mitochondrial-cytochrome-C) biomarkers exhibited a pattern identical to that of LVEF, whereas angiogenesis factors (VEGF/CXCR4/SDF-1α) showed significant progressive increase among all groups (all p<0.0001). Microscopic findings of CD31+cells/vWF+cells/small-vessel density/sarcomere-length showed an identical pattern, whereas collagen-deposition area/fibrotic area/apoptotic nuclei expressed an opposite pattern compared to that of LVEF among all groups (all p<0.0001). In conclusion, CKD aggravated ischemia-induced LV dysfunction and remodeling and molecular-cellular perturbations that were reversed by ECSW treatment.


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