Functional and electrical integration of engineered heart tissue in a native rat heart

Objectives: Due to a considerable shortage in donor hearts for transplantation facing an increasing number of possible recipients, there is an urgent need for the development of alternative techniques such as engineering of artificial heart tissue. This requires, however, that the engineered heart tissue (EHT) can integrate into native heart. The most sensitive factor is electrical communication and regular propagation of an action potential between EHT and native tissue.

Methods: We tested, whether EHT, produced from neonatal rats, implanted for 4 weeks into a rat with a 2 weeks myocardial infarction (LAD-occlusion), allows normal action potential propagation, using a 256 channel potential mapping system allowing to monitor epicardial potentials synchronously at 256 ventricular sites.

Results: Infarction led to conduction delay in the occluded area (15±3 (infarcted) vs. 5±1 ms (non-ischemic, n=6). In EHT-treated-infarcted hearts we found a homogenous activation wavefront without significant delay (5.5±1 ms, EHT+infarct). Delivery of rectangular pulses to the EHT led a propagated response from EHT to native heart. Longitudinal and transverse conduction velocity was similar in EHT as in native tissue and anisotropy (=VL/VT) was nearly identical (normal: 4.07±0.91; EHT: 4.15±0.8). Gap junctional uncoupling of the hearts by lowering pH (from 7.36 to 6.7) led to uncoupling between EHT and native heart showing that they were previously well coupled. Fibroblast EHT (sham EHT) did not exhibit any active response.

Conclusion: EHT can integrate into native heart tissue and bidirectional communication between EHT and native tissue is possible with biophysical properties very similar to native heart. Thus, EHT opens a new interesting alternative technology.