Key result
KCa2 inhibitor ICA reduces stretch-induced AERP shortening by ~71%, lowering vulnerability to AF.
Why the study?
The study evaluated whether SK2.x channel inhibitors can prevent stretch-induced shortening of AERP and protect the heart from AF.
Does the small conductance calcium activated K+ channel inhibitor ICA prevent stretch-induced shortening of AERP and protect against AF in an isolated perfused rabbit heart model?
Does the small conductance calcium activated K+ channel inhibitor ICA prevent stretch-induced shortening of AERP and protect against AF in an isolated perfused rabbit heart model?
In a preclinical rabbit heart model, the small conductance calcium-activated K+ channel inhibitor ICA attenuated stretch-induced shortening of atrial refractoriness and decreased vulnerability to atrial fibrillation.
Answers are grounded in this paper and cite their sources.
ICA attenuates stretch-induced AF vulnerability in rabbit hearts; hypothesis-generating for KCa2 inhibition in human AF.
OBJECTIVES: 2.x channel inhibitors can prevent the stretch induced shortening of AERP and protect the heart from AF. METHODS: 2 channel inhibitor (N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) 1 µM) was investigated using the isolated perfused rabbit heart preparation. To stretch the left atrium (LA) a balloon was inserted and inflated. AERP and action potential duration (APD) were recorded before and after atrial stretch. AF was induced by burst pacing the LA at different degrees of atrial stretch. RESULTS: 2 inhibitor ICA significantly attenuated the stretch induced shortening of AERP to 2.5 ± 1.1 ms. Total AF duration increased linearly with atrial balloon pressure. This relationship was not found in the presence of ICA. ICA lowered the incidence of AF induction and total AF duration. CONCLUSION: 2 channel inhibitor ICA attenuates the acute stretch induced shortening of AERP and decreases stretch induced vulnerability to AF.
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Yan et al. (2021) studied Atrial fibrillation (n=35). ICA (KCa2 channel inhibitor) vs. Vehicle (DMSO) was evaluated on Stretch-induced shortening of atrial effective refractory period (AERP) from 0 to 20 mmHg (p=0.0038). The KCa2 channel inhibitor ICA attenuated acute stretch-induced shortening of the atrial effective refractory period and decreased vulnerability to atrial fibrillation.
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