Induced functional modulations of isolated large mammalian hearts

Howard, Brian T.; Iaizzo, Paul A.

doi:10.1007/s00424-019-02277-0

Cited by 1 publication

(1 citation statement)

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“…However, it is predominantly used in rodent animal models only due to the complexities involved in developing large animal and human Langendorff systems, as well as challenges in the acquisition of these organs. Although there have been previous attempts to carry out studies in intact ex vivo human hearts, these have been achieved in only a handful of centres due to the aforementioned challenges [ 7 , 8 , 16 ]. To date, no work has been published on the utility of this model for assessing the electrophysiology changes under pharmacological intervention.…”

Section: Introductionmentioning

confidence: 99%

Development of a pro-arrhythmic ex vivo intact human and porcine model: cardiac electrophysiological changes associated with cellular uncoupling

Brook

Kim

Koutsoftidis

et al. 2020

Pflugers Arch - Eur J Physiol

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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. A total of 1 mM of carbenoxolone was administered at 5 ml/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 ± 4.1–67.2 ± 2.7 ms) indicating conduction slowing. The features with the largest percentage change between baseline and 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 pro-arrhythmic substrates.

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Section: Introductionmentioning

confidence: 99%