Investigation of Transmural Atrial Tissue Biomimetic Culture for the Development of an Atrial Fibrillation Model

Background: The development of an atrial tissue culture model could open the pathway to more in-depth investigations on atrial fibrillation and for individualized drug response testing in the framework of personalized medicine. In this article, we compared the standard trabecular atrial tissue preparation technique (St) with our new transmural technique (TM) which in a more physiological real-life manner includes all three layers of the atrial wall.

Method: Following informed consent, atrial tissue was collected from the atrial cannulation site of patients undergoing coronary artery bypass grafting, transferred to a cardioplegic solution and stored at 4°C. Trabecular samples were prepared by dissecting a thin muscle trabecula from the atrial tissue wall; transmural samples were cut manually such as to include the complete cardiac triple layer of endocardium, myocardium, and epicardium. The samples were transferred to a culture chamber and cultivated under electrical stimulation, with a diastolic preload of 1.5 mN and a stimulation frequency of 0.5 Hz for at least 21 days. Atrial sample contractility and related electrophysiological parameters were investigated on day 7; histological preparation was performed on days 7 and 21.

Results: All contractile samples showed a prompt decrease in contractility within 1 hour of culture initiation for a total of 5 to 7 days with a systematic increase of contractility thereafter. Thirteen contractile samples from seven patients were cultured. Contractile refractory periods (St: 280 ± 0 milliseconds, TM: 276 ± 67 milliseconds, p = 0.9), stimulation thresholds (St: 31 ± 10 mA, TM: 33 ± 20 mA, p = 0.8), and maximum captured frequency (St: 240 ± 0 bpm, TM: 240 ± 0 bpm) were similar between the groups. Histological examination after 21 days of culture showed intact and vivid cell structures with slight dispersion of Connexin-43 as well as an altered connective and muscular tissue morphology in trabecular as well as transmural samples.

Conclusion: Development of a transmural atrial tissue model could be beneficial over a trabecular model, as data have shown that the combination of all cardiac layers is important in a multitude of cardiac functions and disease processes (including atrial fibrillation). Here, we compared our transmural technique with the standard trabecular method and found comparable short-term results. Further work will investigate vitality and long-term durability of the ex vivo biomimetic model especially related to atrial fibrillation induction and drug testing.

Publikationsverlauf

Artikel online veröffentlicht:
28. Januar 2023