Key result
Irbesartan prevents AF in paced dogs by increasing cardiac sodium currents and Nav1.5 expression.
Why the study?
Does irbesartan prevent sodium channel remodeling in a canine model of atrial fibrillation?
RCT (n=18)
randomized
Does irbesartan prevent sodium channel remodeling in a canine model of atrial fibrillation?
In a canine model of atrial fibrillation, irbesartan prevented sodium channel remodeling by increasing sodium current densities and Nav1.5 expression.
Irbesartan may attenuate sodium channel remodeling in canine AF; leaves open translation to human therapy.
Introduction: Activation of the renin-angiotensin system (RAS) plays an important role in atrial electrical remodeling (AER). The purpose of the present study was to evaluate the effects of irbesartan on cardiac sodium current (I Na ) in a canine model of atrial fibrillation. Materials and methods: Eighteen dogs were randomized into sham, pacing or pacing+irbesartan groups ( n = 6 in each group). The dogs in the pacing and irbesartan group were paced at 500 bpm for two weeks. Irbesartan (60 mg·kg −1 ·d −1 ) was administered orally in the pacing+irbesartan groups. I Na was recorded using the whole-cell patch clamp technique from canine atrial myocytes. The expressions of cardiac Na + channels (Nav1.5) mRNA were semi-quantified by reverse transcription-polymerase chain reaction. Results: Our results showed that I Na density and Nav1.5 mRNA expression in the pacing group decreased significantly ( p < 0.05 vs. sham). However, rapid atrial pacing had no effects on the half-activation voltage (V 1/2act ) and half-inactivation voltage (V 1/2inact ) of I Na ( p > 0.05 vs. sham). Irbesartan significantly increased I Na densities and gene expression and hyperpolarized V 1/2act without concomitant changes in V 1/2inact . Conclusions: Irbesartan significantly increased I Na densities, which contributed to improving intra-atrial conduction and prevented the induction and promotion of AF in atrial pacing dogs.
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Wang et al. (2018) conducted an RCT in atrial fibrillation (canine model) (n=18). Irbesartan vs. sham and pacing alone was evaluated on cardiac sodium current (INa) density and Nav1.5 mRNA expression. Irbesartan significantly increased cardiac sodium current densities and Nav1.5 gene expression, preventing the induction and promotion of atrial fibrillation in paced dogs.
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