Magnetics-Based Approach for Fine-Tuning Afterload
in Engineered Heart Tissues
Version 2 2019-09-16, 23:45Version 2 2019-09-16, 23:45
Version 1 2019-06-24, 20:03Version 1 2019-06-24, 20:03
Posted on 2019-09-16 - 23:45
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 technique was employed to sequentially increase afterload
applied to rat engineered heart tissues (rEHTs) over a 7-day period.
Over the observation period, the contractile properties of rEHTs grown
on control posts marginally increased. 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 three-fold higher than for 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 h. 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 temporarily 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.
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Rodriguez, Marita
L.; Werner, Tessa R.; Becker, Benjamin; Eschenhagen, Thomas; Hirt, Marc N. (2019). Magnetics-Based Approach for Fine-Tuning Afterload
in Engineered Heart Tissues. ACS Publications. Collection. https://doi.org/10.1021/acsbiomaterials.8b01568