The development of new biomechanical strategy for the treatment of post-MI ventricular remodeling

• Project/Area Number: 18K08608
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kindai University (2018, 2020-2022); Kobe University (2019)
• Principal Investigator: Takaba Kiyoaki 近畿大学, 医学部, 非常勤講師 (00528573)
• Co-Investigator(Kenkyū-buntansha): 松村 和明 北陸先端科学技術大学院大学, 先端科学技術研究科, 教授 (00432328) ; 中井 隆介 京都大学, こころの未来研究センター, 特定講師 (10576234) ; 東 高志 京都大学, 工学研究科, 特定研究員 (40378899) ; 瀧川 敏算 京都大学, 工学研究科, 教授 (50201603) ; 中村 達雄 京都大学, ウイルス・再生医科学研究所, 准教授 (70227908) ; 坂口 元一 近畿大学, 医学部, 教授 (60603363)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 心不全 / 心筋リモデリング / ハイドロジェル / シミュレーション / 大動脈瘤 / バイオメカニクス / 梗塞後心筋リモデリング / 大動脈解離 / 壁応力 / NO産生因子 / ノコンポジット・ジェル / 拡散強調像 / 梗塞後心室リモデリング / ハイドロゲル

Outline of Final Research Achievements

The MRI for animals was discarded as its aging. Then, we had to change our research method from using in-vivo to ex-vivo porcine heart. We injected the nanocomposite gels with various viscosity into the apex of ex-vivo heart, by changing the ratio of PMN to PLL（％). And then we calculated the complexity of myofiber angles from DW images by using the MRI for patients. By analyzing these data, we showed that the best ratio for intra-myocardial gel distribution was 4%. However, the MRI study was severely restricted and became practically impossible, because of COVID-19 pandemic. We had to start the clinical simulation research with the help of Bioinformatics laboratory, Ritsumeikan University. Using the clinical chest CT images, we created configuration models of the aorta and applied blood flow simulations on these models. By using these simulation data, we developed the novel and feasible method to estimate the wall tension from the distribution of the curvature radius of the aorta.

Academic Significance and Societal Importance of the Research Achievements

梗塞後心筋リモデリングに対する治療として心外膜に厚さわずか数ミリのシートを張り付ける手法が注目されているが、壁応力を改善するために十分な心筋の厚さを得る事は困難であることは明白である。一方、ナノコンポジット・ジェルは粘性度を最適化することにより健常心筋の配列を阻害することなく心筋内注入が可能であることが判明し、心不全パンデミックの時代にハイドロジェル心筋内注入がり効果的な治療手法となりうることが示唆される。
また、今回我々が開発した血管形状モデルの曲率半径の分布から壁張力を求める方法は大動脈瘤破裂部位の予測および大動脈ステント留置後のリーク発生の予測に応用できることが示唆される。

Research Products

• [Journal Article] Myocardial injection of a thermoresponsive hydrogel with reactive oxygen species scavenger properties improves border zone contractility (2020)
  • Author(s): Spaulding Kimberly A.、Zhu Yang、Takaba Kiyoaki、Ramasubramanian Anusuya、Badathala Anusha、Haraldsson Henrik、Collins Alexander、Aguayo Esteban、Shah Curran、Wallace Arthur W.、Ziats Nicholas P.、Lovett David H.、Baker Anthony J.、Healy Kevin E.、Ratcliffe Mark B.
  • Journal Title: Journal of Biomedical Materials Research Part A Volume: 108 Issue: 8 Pages: 1736-1746
  • DOI: 10.1002/jbm.a.36941
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Left ventricular geometry during unloading and the end-systolic pressure volume relationship: Measurement with a modified real-time MRI-based method in normal sheep (2020)
  • Author(s): Giao Duc M.、Wang Yan、Rojas Renan、Takaba Kiyoaki、Badathala Anusha、Spaulding Kimberly A.、Soon Gilbert、Zhang Yue、Wang Vicky Y.、Haraldsson Henrik、Liu Jing、Saloner David、Guccione Julius M.、Ge Liang、Wallace Arthur W.、Ratcliffe Mark B.
  • Journal Title: PLOS ONE Volume: 15 Issue: 6 Pages: 0234896-0234896
  • DOI: 10.1371/journal.pone.0234896
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility. (2018)
  • Author(s): Spaulding K, Takaba K, Collins A, Faraji F, Wang G, Aguayo E, Ge L, Saloner D, Wallace AW, Baker AJ, Lovett DH, Ratcliffe MB.
  • Journal Title: PLoS One Volume: 13 Issue: 2 Pages: e0192720-e0192720
  • DOI: 10.1371/journal.pone.0192720
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Estimation of Vasodilator Distribution for Improvement in Risk Estimation of Thoracic Aortic Re-dissection (2023)
  • Author(s): Kiyoaki Takaba
  • Organizer: 第62回生体医工学会