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Basic fibroblast growth factor attenuates left-ventricular remodeling following surgical ventricular restoration in a rat ischemic cardiomyopathy model

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Abstract

Objective

Although surgical ventricular restoration for ischemic cardiomyopathy is expected as an alternative or bridge to heart transplantation, post-operative remodeling of left ventricle (LV) needs to be addressed. This study aimed to examine the effect of basic fibroblast growth factor (bFGF), which induces angiogenesis and tissue regeneration in ischemic myocardium, to prevent remodeling after surgical ventricular restoration (SVR) using a rat ischemic cardiomyopathy model.

Methods

Four weeks after coronary artery ligation, rats were divided into two groups: rats treated with SVR alone (SVR; n = 21), and rats treated with SVR and local sustained release of bFGF using gelatin hydrogel sheet (SVR + bFGF; n = 22). Cardiac function was assessed by serial echocardiography and cardiac catheterization. Cardiac tissue sections were histologically examined for vascular density and fibrosis.

Results

Higher systolic function and lower LV end-diastolic pressure (LVEDP) were observed in rats treated with SVR + bFGF (SVR vs SVR + bFGF; Ees: 0.22 ± 0.11 vs 0.33 ± 0.22 mmHg/μL, p = 0.0328; LVEDP: 12.7 ± 7.0 vs 8.5 ± 4.3 mmHg, p = 0.0230). LV area tended to be lower in rats treated with SVR + bFGF compared to rats treated with SVR alone (left-ventricular end-diastolic area: 0.66 ± 0.07 vs 0.62 ± 0.07 cm2, p = 0.071). Vascular density tended to be higher in rats treated with SVR + bFGF than those without bFGF (23.3 ± 8.1 vs 28.8 ± 9.5/mm2, p = 0.0509).

Conclusions

BFGF induced angiogenesis and attenuated remodeling after SVR which secured the efficacy of SVR in a rat ischemic cardiomyopathy model.

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Acknowledgments

This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (to T.I.) [Grant Number 22591540]. We are grateful to Mrs. F. Kataoka (Kyoto Univ.) for assistances in histological studies, and to Dr. A. Sugimoto (Kyoto Univ.) for assistance with surgical procedures and examinations such as echocardiography and cardiac catheterization. We thank Dr. Hemant Poudyal (Kyoto Univ.) for critical reading of the manuscript.

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Author notes

  1. Atsushi Nagasawa

    Present address: Department of Cardiovascular Surgery, Kokura Kinen Hospital, Kitakyushu, Japan

  2. Shigeki Yanagi

    Present address: Department of Cardiovascular Surgery, Kumamoto Central Hospital, Kumamoto, Japan

  3. Naoki Kanemitsu

    Present address: Department of Cardiovascular Surgery, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan

Authors and Affiliations

  1. Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Atsushi Nagasawa, Hidetoshi Masumoto, Shigeki Yanagi, Naoki Kanemitsu, Tadashi Ikeda & Kenji Minatoya

  2. Laboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan

    Yasuhiko Tabata

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  1. Atsushi Nagasawa
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Correspondence to Kenji Minatoya.

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Nagasawa, A., Masumoto, H., Yanagi, S. et al. Basic fibroblast growth factor attenuates left-ventricular remodeling following surgical ventricular restoration in a rat ischemic cardiomyopathy model. Gen Thorac Cardiovasc Surg 68, 311–318 (2020). https://doi.org/10.1007/s11748-019-01187-3

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