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May 31, 2021Frontiers in Cardiovascular MedicineOpen Access

Inhibition of KCa3.1 Channels Suppresses Atrial Fibrillation via the Attenuation of Macrophage Pro-inflammatory Polarization in a Canine Model With Prolonged Rapid Atrial Pacing

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Why the study?

To investigate the role of KCa3.1 inhibition in macrophage pro-inflammatory polarization and vulnerability to AF in a canine model with prolonged rapid atrial pacing.

Does TRAM-34 reduce vulnerability to AF and macrophage pro-inflammatory polarization in a canine model of rapid atrial pacing?

Population

Twenty beagle dogs weighing 8–10 kg

Comparison

Sham vs pacing alone vs pacing plus TRAM-34

Design

Randomized animal study

Follow-up

7 days

Key result

Inhibition of KCa3.1 with TRAM-34 significantly reduced the mean duration of atrial fibrillation from 37.29 seconds to 4.71 seconds in a canine model of prolonged rapid atrial pacing.

Authors

SHShanqing HeYWYoucheng WangYYYajun Yao

Discussion

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Member takes

Overview

Hypothesis-generating in canine AF model; human trials needed before considering KCa3.1 inhibition clinically.

Structured PICO

Does TRAM-34 reduce vulnerability to AF and macrophage pro-inflammatory polarization in a canine model of rapid atrial pacing?

P
Population
20 male beagle dogs underwent prolonged rapid atrial pacing for 7 days to evaluate the effect of KCa3.1 inhibition on atrial fibrillation vulnerability.
I
Intervention
TRAM-34 (KCa3.1 blocker) 10 mg/kg by slow intravenous injection 3 times each day for 7 days, alongside continuous rapid atrial pacing (450 beats/min)
C
Comparator
Sham group (pacemaker implanted without pacing) and pacing group (rapid atrial pacing + vehicle infusion)
O
Outcome
Vulnerability to AF (inducibility, duration, atrial effective refractory period) and macrophage pro-inflammatory polarization markers (IL-1β, MCP-1, TNF-α, CD68, iNOS, Arg-1)surrogate

Main Result

Absolute Event Rate: 4.71% vs 37.29%

p-value: p=<0.05

Inhibition of KCa3.1 with TRAM-34 suppresses vulnerability to AF by attenuating macrophage pro-inflammatory polarization in a canine model.

Limitations

  • Did not confirm the inhibitory effect of TRAM-34 on macrophage polarization in cellular experiments.
  • Failed to distinguish between circulating monocytes and cardiac-resident macrophages.
  • Optimal stimulation parameters for TRAM-34 on macrophages have not been fully determined.

Cite This Study

He et al. (2021) studied Atrial fibrillation (n=20). TRAM-34 vs. Pacing (vehicle) and Sham was evaluated on Mean duration of atrial fibrillation (seconds) (p=<0.05). Inhibition of KCa3.1 with TRAM-34 significantly reduced the mean duration of atrial fibrillation from 37.29 seconds to 4.71 seconds in a canine model of prolonged rapid atrial pacing.

synapsesocial.com/papers/6a1ff6203224f8dacd0dafe7https://doi.org/10.3389/fcvm.2021.656631
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