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Rodriguez ML, Werner TR, Becker B, et al. A magnetics-based approach for fine-tuning afterload in engineered heart tissues. ACS Biomater Sci Eng. 2019;5(7):3663-3675doi: 10.1021/acsbiomaterials.8b01568.
Rodriguez, M. L., Werner, T. R., Becker, B., Eschenhagen, T., & Hirt, M. N. (2019). A magnetics-based approach for fine-tuning afterload in engineered heart tissues. ACS biomaterials science & engineering, 5(7), 3663-3675. https://doi.org/10.1021/acsbiomaterials.8b01568
Rodriguez, Marita L, et al. "A magnetics-based approach for fine-tuning afterload in engineered heart tissues." ACS biomaterials science & engineering vol. 5,7 (2019): 3663-3675. doi: https://doi.org/10.1021/acsbiomaterials.8b01568
Rodriguez ML, Werner TR, Becker B, Eschenhagen T, Hirt MN. A magnetics-based approach for fine-tuning afterload in engineered heart tissues. ACS Biomater Sci Eng. 2019 Jul 08;5(7):3663-3675. doi: 10.1021/acsbiomaterials.8b01568. Epub 2019 Jun 11. PMID: 31637285; PMCID: PMC6803165.
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ACS Biomater Sci Eng. 2019 Jul 08;5(7):3663-3675. doi: 10.1021/acsbiomaterials.8b01568. Epub 2019 Jun 11.

A magnetics-based approach for fine-tuning afterload in engineered heart tissues.

ACS biomaterials science & engineering

Marita L Rodriguez, Tessa R Werner, Benjamin Becker, Thomas Eschenhagen, Marc N Hirt

Affiliations

  1. Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
  2. DZHK (German Center for Cardiovascular Research), Partner site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany.

PMID: 31637285 PMCID: PMC6803165 DOI: 10.1021/acsbiomaterials.8b01568

Abstract

Afterload plays important roles during heart development and disease progression, however, studying these effects in a laboratory setting is challenging. Current techniques lack the ability to precisely and reversibly alter afterload over time. Here, we describe a magnetics-based approach for achieving this control and present results from experiments in which this device was employed to sequentially increase afterload applied to rat engineered heart tissues (rEHTs) over a 7-day period. The contractile properties of rEHTs grown on control posts marginally increased over the observation period. The average post deflection, fractional shortening, and twitch velocities measured for afterload-affected tissues initially followed this same trend, but fell below control tissue values at high magnitudes of afterload. However, the average force, force production rate, and force relaxation rate for these rEHTs were consistently up to 3-fold higher than in control tissues. Transcript levels of hypertrophic or fibrotic markers and cell size remained unaffected by afterload, suggesting that the increased force output was not accompanied by pathological remodeling. Accordingly, the increased force output was fully reversed to control levels during a stepwise decrease in afterload over 4 hours. Afterload application did not affect systolic or diastolic tissue lengths, indicating that the afterload system was likely not a source of changes in preload strain. In summary, the afterload system developed herein is capable of fine-tuning EHT afterload while simultaneously allowing optical force measurements. Using this system, we found that small daily alterations in afterload can enhance the contractile properties of rEHTs, while larger increases can have temporary undesirable effects. Overall, these findings demonstrate the significant role that afterload plays in cardiac force regulation. Future studies with this system may allow for novel insights into the mechanisms that underlie afterload-induced adaptations in cardiac force development.

Keywords: afterload; engineered heart tissues (EHTs); magnetics; maturation

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