Golestan University of Medical Sciences Repository

Frequency-dependent protective role of simvastatin in electrophysiological remodeling of AF and in terminating experimental AVRT mediated via KATP opening and endogenous Nitric Oxide (NO)

Khori, V. and Nayebpour, M. (2011) Frequency-dependent protective role of simvastatin in electrophysiological remodeling of AF and in terminating experimental AVRT mediated via KATP opening and endogenous Nitric Oxide (NO). EUROPEAN HEART JOURNAL, 32 (1). pp. 942-943.

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Abstract

Purpose: The purposes of the present study are to determine (1) whether Simvastatin modifies the rate-dependent AV nodal conduction and refractoriness to terminate experimental AVRT and AF and (2) to determine protective signaling mechanism of Simvastatin via opening of KATP, blocking of MPTP and inhibiting endogenous Nitric Oxide (NO). Methods: Selective stimulation protocols and mathematical formulations were used to assess basic AV-nodal conduction and refractoriness (AVERP & AVFRP) and to induce simulated experimental AVRT model in various cycle lengths in isolated perfused rabbit AV nodal preparation in 5 groups (N=45). AF was simulated by high-rate atrial pacing with random coupling intervals)75-150ms). The stimulation protocols were carried out during control conditions and in the presence of various concentrations of Simvastatin (0.5,1,5,10 μm), Cyclosporine (1μm), Glibenclamide (5μm), L-NAME (50μm). Results: Simvastatin in concentration-dependent manner prolonged nodal ERP, FRP and Wenckebach cycle length. Simvastatin suppressed simulated AV reentrant tachycardia in concentration-dependent manner by increasing the positive slope of the relation between /RT, causing arrhythmia wavelength index (λ) be reached at 1 in a slower rate. Excitable gap (ERP-AH) increased by high concentration of Simvastatin (5 μm). Prolongation of H-H interval and increased number of concealed beats was observed during AF protocol by simvastatin (5,10 μM).L-Name and Glibenclamid only abolished the effects of simvastatin (5 μm) on the frequency-dependent prolongation of the zone of concealment at various cycle lengths and average H-H interval during AF. In contrast, pretreatment with a selective MPTP blocker, cyclosporine, didn’t reverse protective effects of simvastatin. Conclusion: Increasing AV-nodal refractory period, zone of concealment and excitable gap are protectivemechanisms of simvastatin in slowing ventricular rhythm during atrial fibrillation. Tachycardia-related suppression and termination of AVRT is major mechanisms of simvastatin by increasing AV nodal refractory period than conduction time. Anti-AF effects are dependent upon KATP channel activation and endogenous NO while other mechanisms are involved in its Anti-AVRT effects.

Item Type: Article
Subjects: موارد کلی
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 27 Apr 2015 09:42
Last Modified: 21 Jun 2017 15:03
URI: http://eprints.goums.ac.ir/id/eprint/3949

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