Key result
Isoproterenol alone and combined with SK channel block terminated rotors at 0.01 and 0.1 µM ACh in a computational AF model, whereas SK block alone only worked at the lower concentration.
Why the study?
The individual and combined effects of SK channel block and isoproterenol in terminating stable rotors in cholinergic paroxysmal AF were not established.
Does Isoproterenol and/or SK channel block terminate rotors in a computational model of cholinergic paroxysmal atrial fibrillation?
Does Isoproterenol and/or SK channel block terminate rotors in a computational model of cholinergic paroxysmal atrial fibrillation?
Computational modeling demonstrates that beta-adrenergic stimulation and SK channel block can terminate rotors in a model of cholinergic paroxysmal atrial fibrillation.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for rotor termination strategies; requires validation in experimental models before any clinical consideration.
Hyperactivity of the parasympathetic nervous system has been linked to the onset of paroxysmal atrial fibrillation (AF). Recent investigations have proven inhibition of small-conductance calcium-activated potassium (SK) channels to improve adverse cholinergic effects in the atria. It has also been reported that <tex>β</tex> -adrenergic stimulation by Isoproterenol (Iso) can act as a brake to lessen cholinergic effects on atrial tissue. Furthermore, the combination of SK channel block (SKb) and Iso has been suggested to possibly prolong atrial APD in ACh-stimulated myocytes. In this study, computational modeling was used to test individual and combined effects of SKb and Iso in terminating a stable rotor in a cholinergic AF model of human atria. 2D tissues with uniform ACh concentrations of 0.01 or <tex>0.1μ M</tex> were simulated. After stable rotors were initiated, <tex>1μ M</tex> Iso and/or complete SKb were progressively applied over time following different application kinetics. Both Iso alone and the combination of Iso and SKb were able to terminate rotors for the two ACh concentrations. SKb was only able to terminate the rotor for the lower ACh concentration. In conclusion, the results from this study support <tex>β</tex> -adrenergic stimulation and SK channel block, the latter with less efficacy, as potential options to terminate rotors in parasympathetically-stimulated human atria.
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Celotto et al. (2021) studied Cholinergic Paroxysmal Atrial Fibrillation. Isoproterenol and/or SK channel block was evaluated on Termination of stable rotors. Isoproterenol alone and combined with SK channel block terminated rotors at 0.01 and 0.1 µM ACh in a computational AF model, whereas SK block alone only worked at the lower concentration.
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