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@article{Brook:2020:10.1007/s00424-020-02446-6,
author = {Brook, J and Kim, M-Y and Koutsoftidis, S and Pitcher, D and Agha-Jaffar, D and Sufi, A and Jenkins, C and Tzortzis, K and Ma, S and Jabbour, R and Houston, C and Handa, B and Li, X and Chow, J-J and Jothidasan, A and Bristow, P and Perkins, J and Harding, S and Bharath, A and Ng, FS and Peters, N and Cantwell, C and Chowdhury, R and Brook, J and Kim, M-Y and Koutsoftidis, S and Pitcher, D and Agha-Jaffar, D and Sufi, A and Jenkins, C and Tzortzis, K and Ma, S and Jabbour, R and Houston, C and Handa, B and Li, X and Chow, J-J and Jothidasan, A and Bristow, P and Perkins, J and Harding, S and Bharath, A and Ng, FS and Peters, N and Cantwell, C and Chowdhury, R},
doi = {10.1007/s00424-020-02446-6},
journal = {Pflügers Archiv European Journal of Physiology},
pages = {1435--1446},
title = {Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling},
url = {http://dx.doi.org/10.1007/s00424-020-02446-6},
volume = {472},
year = {2020}
}

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TY  - JOUR
AB  - We describe a human and large animal Langendorff experimental apparatus for live electrophysiological studies and measure the electrophysiological changes due to gap-junction uncoupling in human and porcine hearts. The resultant ex vivo intact human and porcine model can bridge the translational gap between smaller simple laboratory models and clinical research. In particular, electrophysiological models would benefit from the greater myocardial mass of a large heart due to its effects on far field signal, electrode contact issues and motion artefacts, consequently more closely mimicking the clinical setting Porcine (n=9) and human (n=4) donor hearts were perfused on a custom-designed Langendorff apparatus. Epicardial electrograms were collected at 16 sites across the left atrium and left ventricle. 1mM of carbenoxolone was administered at 5ml/min to induce cellular uncoupling, and then recordings were repeated at the same sites. Changes in electrogram characteristics were analysed.We demonstrate the viability of a controlled ex vivo model of intact porcine and human hearts for electrophysiology with pharmacological modulation. Carbenoxolone reduces cellular coupling and changes contact electrogram features. The time from stimulus artefact to (-dV/dt)max increased between baseline and carbenoxolone (47.9±4.1ms to 67.2±2.7ms) indicating conduction slowing. The features with the largest percentage change between baseline to Carbenoxolone were Fractionation +185.3%, Endpoint amplitude -106.9%, S-Endpoint Gradient +54.9%, S Point, -39.4%, RS Ratio +38.6% and (-dV/dt)max -20.9%.The physiological relevance of this methodological tool is that it provides a model to further investigate pharmacologically-induced proarrhythmic substrates.
AU  - Brook,J
AU  - Kim,M-Y
AU  - Koutsoftidis,S
AU  - Pitcher,D
AU  - Agha-Jaffar,D
AU  - Sufi,A
AU  - Jenkins,C
AU  - Tzortzis,K
AU  - Ma,S
AU  - Jabbour,R
AU  - Houston,C
AU  - Handa,B
AU  - Li,X
AU  - Chow,J-J
AU  - Jothidasan,A
AU  - Bristow,P
AU  - Perkins,J
AU  - Harding,S
AU  - Bharath,A
AU  - Ng,FS
AU  - Peters,N
AU  - Cantwell,C
AU  - Chowdhury,R
AU  - Brook,J
AU  - Kim,M-Y
AU  - Koutsoftidis,S
AU  - Pitcher,D
AU  - Agha-Jaffar,D
AU  - Sufi,A
AU  - Jenkins,C
AU  - Tzortzis,K
AU  - Ma,S
AU  - Jabbour,R
AU  - Houston,C
AU  - Handa,B
AU  - Li,X
AU  - Chow,J-J
AU  - Jothidasan,A
AU  - Bristow,P
AU  - Perkins,J
AU  - Harding,S
AU  - Bharath,A
AU  - Ng,FS
AU  - Peters,N
AU  - Cantwell,C
AU  - Chowdhury,R
DO  - 10.1007/s00424-020-02446-6
EP  - 1446
PY  - 2020///
SN  - 0031-6768
SP  - 1435
TI  - Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling
T2  - Pflügers Archiv European Journal of Physiology
UR  - http://dx.doi.org/10.1007/s00424-020-02446-6
UR  - https://link.springer.com/article/10.1007%2Fs00424-020-02446-6
UR  - http://hdl.handle.net/10044/1/81864
VL  - 472
ER  -

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