Acute effects of simvastatin to terminate fast reentrant tachycardia through increasing wavelength of atrioventricular nodal reentrant tachycardia circuit

Abstract

Simvastatin (SV) leads to reduction of ventricular rhythm during atrial fibrillation on rabbit atrioventricular (AV) nodes. The aim of our study was (i) to determine the frequency-dependent effects of SV in a functional model, and (ii) to assess the effects of SV to suppress experimental AV nodal reentrant tachycardia (AVNRT). Selective stimulation protocols were used with two different pacing protocols, His to atrial, and atrial to atrial (AA). An experimental AVNRT model with various cycle lengths was created in three groups of perfused rabbit AV nodal preparations (n = 24) including: SV 3 μm, SV 7 μm, and verapamil 0.1 μm. SV increased nodal conduction time and refractoriness by AA pacing. Different simulated models of slow/fast and fast/slow reentry were induced. SV caused inhibitory effects on the slow anterograde conduction (origin of refractoriness) more than on the fast anterograde conduction time, leading to an increase of tachycardia cycle length, tachycardia wavelength and termination of slow/fast reentrant tachyarrhythmia. Verapamil significantly suppressed the basic and frequency-dependent intrinsic nodal properties. In addition, SV decreased the incidence of gap and echo beats. The present study showed that SV in a concentration and rate-dependent manner increased the AV effective refractory period and reentrant tachycardia wavelength that lead to slowing or termination of experimental fast AVNRT. The direction-dependent inhibitory effect of SV on the anterograde and retrograde dual pathways explains its specific antireentrant actions.

Simvastatin activates single skeletal RyR1 channels but exerts more complex regulation of the cardiac RyR2 isoform

“…Interestingly, simvastatin was found to reduce fast reentrant arrthymias in a rabbit model of experimental atrioventricular nodal reentrant tachycardia (Khori et al, ). In relation to our results, it is conspicuous that statins have previously been reported to be associated with a decrease in instances of atrial fibrillation (AF) (Siu et al, ; Young‐Xu et al, ; Amar et al, ) and ventricular arrhythmias in high‐risk patients (De Sutter et al, ).…”

The effects of serotonin on the electrophysiological properties of atrioventricular node during an experimental atrial fibrillation

“…Wenckebach cycle length (WBCL), atrial-His conduction time (AH), effective refractory period (ERP), functional refractory period (FRP), and the frequency-dependent nodal variables (recovery, facilitation, and fatigue) were measured as previously explained (Khori et al 2015). Differences between AH and ERP were measured as an excitability index, which indicated a relative effect of a drug on AH prolongation against refractoriness.…”

“…ZOC was calculated as the difference between atrial refractoriness (AERP) and nodal refractoriness (NERP). In addition, differences between AH and ERP were measured as the excitability index, indicating the drug's relative effect on nodal conduction time prolongation against refractoriness (Khori et al 2012b(Khori et al , 2015. The AV nodal gap (conduction gap) refers to the duality of the AV node and is defined as a window of each coupling interval, within which the atrial stimulus was not conducted through the AV node.…”

“…The AV nodal gap (conduction gap) refers to the duality of the AV node and is defined as a window of each coupling interval, within which the atrial stimulus was not conducted through the AV node. Echo beats (reentry beats), the landmark of a dual pathway, are defined as a single or multiple premature atrial beats that can reenter the AV node during short cycle length stimulation (Khori et al 2015). …”

“…The following drugs were gifts: ketanserin tartrate from Janssen (Beerse, Belgium), (3-tropanyl) 1-H-indole-3-carboxylic acid ester (tropisetron; Novartis, Basel, Switzerland) from Sandoz, and 1-piperidine ethyl 1-H-indole-3-carboxylate (SB203186) from SmithKline Beecham (Harlow, UK). All drugs were dissolved in Krebs and Henseleit buffer (Khori et al 2015). An exception was ketanserin, which was dissolved in lactic acid (0.04 M) before being added to the superfusion solution.…”