Biodegradable vs Nonbiodegradable Cardiac Support Device for Treating Ischemic Cardiomyopathy in a Canine Heart Mutsunori Kitahara, MD, Shigeru Miyagawa,

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Biodegradable vs Nonbiodegradable Cardiac Support Device for Treating Ischemic Cardiomyopathy in a Canine Heart Mutsunori Kitahara, MD, Shigeru Miyagawa, MD, PhD, Satsuki Fukushima, MD, PhD, Atsuhiro Saito, PhD, Ayumi Shintani, PhD, MPH, Toshiaki Akita, MD, PhD, Yoshiki Sawa, MD, PhD Seminars in Thoracic and Cardiovascular Surgery Volume 29, Issue 1, Pages 51-61 (March 2017) DOI: 10.1053/j.semtcvs.2017.01.016 Copyright © 2017 The Authors Terms and Conditions

Figure 1 Implantation of the cardiac support device. (A) Macroscopic view of the nonbiodegradable cardiac support device (left) and the biodegradable cardiac support device (right). (B) The implanted cardiac support device wraps around the entire ventricle. (C) Study protocol of experiment and assessment of cardiac function and histologic analysis. Cardiac support device at 12 weeks after myocardial infarction (MI). Representative photographic images of the heart after implantation of the nonbiodegradable device (D) and the biodegradable device (F). Representative photographic images of the heart (Masson trichrome staining) with the implanted nonbiodegradable device (E) and the biodegradable device (G). Representative hematoxylin and eosin staining of the epicardium. (H) The white arrow points to the nonbiodegradable device. (I) The black arrow points to the granulomatous tissue formed because of the presence of the biodegradable device; there is no evidence of active inflammation. (Color version of figure is available online.) Seminars in Thoracic and Cardiovascular Surgery 2017 29, 51-61DOI: (10.1053/j.semtcvs.2017.01.016) Copyright © 2017 The Authors Terms and Conditions

Figure 2 Multidetector computed tomography analysis. (A) Changes in left ventricular end-systolic volume (LVESV). (B) Changes in left ventricular end-diastolic volume (LVEDV). (C) The variation in LVESV from pretreatment to 12 weeks (ΔLVESV). (D) The variation in LVEDV from pretreatment to 12 weeks (ΔLVEDV). (E) Changes in left ventricular ejection fraction (LVEF). No treatment is denoted by a solid line, nonbiodegradable device is denoted by a dotted line, and biodegradable device is denoted by a dashed-dotted line. *P < 0.02 vs corresponding no treatment, †P < 0.02 vs corresponding nonbiodegradable device, ‡P < 0.03 vs LVEF at pretreatment. (Color version of figure is available online.) Seminars in Thoracic and Cardiovascular Surgery 2017 29, 51-61DOI: (10.1053/j.semtcvs.2017.01.016) Copyright © 2017 The Authors Terms and Conditions

Figure 3 Cardiac catheterization data and global left ventricular wall stress. (A) Ees, end-systolic elastance (P = 0.04, Kruskal-Wallis test). (B) dp/dt max, the maximal rate of change in pressure (P = 0.05, Kruskal-Wallis test). (C) Tau, the time constant of relaxation. (D) −dp/dt min, the minimal rate of change in pressure. (E) EDPVR, end-diastolic pressure-volume relationship. (F) PRSW, preload recruitable stroke work. (G) LVESP, left ventricular end-systolic pressure. (H) LVEDP, left ventricular end-diastolic pressure, (I) global end-systolic wall stress, and (J) global end-diastolic wall stress. RV, right ventricle; LV, left ventricle. (Color version of figure is available online.) Seminars in Thoracic and Cardiovascular Surgery 2017 29, 51-61DOI: (10.1053/j.semtcvs.2017.01.016) Copyright © 2017 The Authors Terms and Conditions

Figure 4 Histologic evaluation at 12 weeks after MI. (A) Myocyte short-axis diameter in the border zones; cardiomyocyte hypertrophy is significantly lower in the treatment groups than in the no-treatment group. (B) Interstitial fibrosis in the border zones; Masson trichrome staining shows significantly less interstitial fibrosis in the treatment groups than in the no-treatment group. (C) Capillary density in the border zones; capillary density is more enhanced in the treatment groups than in the no-treatment group. (Color version of figure is available online.) Seminars in Thoracic and Cardiovascular Surgery 2017 29, 51-61DOI: (10.1053/j.semtcvs.2017.01.016) Copyright © 2017 The Authors Terms and Conditions

The nonbiodegradable (left) and the biodegradable (right) cardiac support devices. Seminars in Thoracic and Cardiovascular Surgery 2017 29, 51-61DOI: (10.1053/j.semtcvs.2017.01.016) Copyright © 2017 The Authors Terms and Conditions