4.8 Article

Physiologic force-frequency response in engineered heart muscle by electromechanical stimulation

期刊

BIOMATERIALS
卷 60, 期 -, 页码 82-91

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.03.055

关键词

Heart; Tissue engineering; Myocardium; Biophysical properties; Force of contraction; Force frequency relationship; Calcium handling; T-tubulation; Maturation

资金

  1. DZHK (German Center for Cardiovascular Research)
  2. German Federal Ministry for Science and Education [BMBF FKZ 13GW0007A]
  3. German Research Foundation [DFG ZI 708/7-1, DFG ZI 708/8-1, DFG ZI 708/10-1, SFB 1002 TP A02, A05, C04, SFB 937 TP A18]
  4. European Union FP7 CARE-MI
  5. NIH [U01 HL099997, R01 HL076485, P41 EB002520]
  6. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL076485, U01HL099997] Funding Source: NIH RePORTER
  7. NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [P41EB002520] Funding Source: NIH RePORTER

向作者/读者索取更多资源

A hallmark of mature mammalian ventricular myocardium is a positive force-frequency relationship (FFR). Despite evidence of organotypic structural and molecular maturation, a positive FFR has not been observed in mammalian tissue engineered heart muscle. We hypothesized that concurrent mechanical and electrical stimulation at frequencies matching physiological heart rate will result in functional maturation. We investigated the role of biomimetic mechanical and electrical stimulation in functional maturation in engineered heart muscle (EHM). Following tissue consolidation, EHM were subjected to electrical field stimulation at 0, 2, 4, or 6 Hz for 5 days, while strained on flexible poles to facilitate auxotonic contractions. EHM stimulated at 2 and 4 Hz displayed a similarly enhanced inotropic reserve, but a clearly diverging FFR. The positive FFR in 4 Hz stimulated EHM was associated with reduced calcium sensitivity, frequency-dependent acceleration of relaxation, and enhanced post-rest potentiation. This was paralleled on the cellular level with improved calcium storage and release capacity of the sarcoplasmic reticulum and enhanced T-tubulation. We conclude that electro-mechanical stimulation at a physiological frequency supports functional maturation in mammalian EHM. The observed positive FFR in EHM has important implications for the applicability of EHM in cardiovascular research. (C) 2015 Published by Elsevier Ltd.

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