Light transmittance in human atrial tissue and transthoracic illumination in rats support translatability of optogenetic cardioversion of atrial fibrillation

Nyns, E.C.A.; Portero, V.; Deng, S.L.; Jin, T.Y.; Harlaar, N.; Bart, C.I.; ... ; Pijnappels, D.A. (2023)

Article / Letter to editor

Background: Optogenetics could offer a solution to the current lack of an ambulatory method for the rapid automated cardioversion of atrial fibrillation (AF), but key translational aspects remain to be studied. Objective: To investigate whether optogenetic cardioversion of AF is effective in the aged heart and whether sufficient light penetrates the human atrial wall. Methods: Atria of adult and aged rats were optogenetically modified to express light-gated ion channels (i.e., red-activatable channelrhodopsin), followed by AF induction and atrial illumination to determine the effectivity of optogenetic cardioversion. The irradiance level was determined by light transmittance measurements on human atrial tissue. Results: AF could be effectively terminated in the remodeled atria of aged rats (97%, n = 6). Subsequently, ex vivo experiments using human atrial auricles demonstrated that 565-nm light pulses at an intensity of 25 mW/mm(2) achieved the complete penetration of the atrial wall. Applying such irradiation onto the chest of adult rats resulted in transthoracic atrial illumination as evidenced by the optogenetic cardioversion of AF (90%, n = 4). Conclusion: Transthoracic optogenetic cardioversion of AF is effective in the aged rat heart using irradiation levels compatible with human atrial transmural light penetration.

• arrhythmia
• atrial fibrillation
• gene therapy
• optogenetics
• translational research

• All authors: Nyns, E.C.A.; Portero, V.; Deng, S.L.; Jin, T.Y.; Harlaar, N.; Bart, C.I.; Brakel, T.J. van; Palmen, M.; Hjortnaes, J.; Ramkisoensing, A.A.; Zhang, G.Q.; Poelma, R.H.; Ordog, B.; Vries, A.A.F. de; Pijnappels, D.A.
• Date: 2023-06-21
• Journal: Journal of Internal Medicine
• DOI: doi:10.1111/joim.13654