Electromechanical effects of 1,25-dihydroxyvitamin d with antiatrial fibrillation activities

J Cardiovasc Electrophysiol. 2014 Mar;25(3):317-23. doi: 10.1111/jce.12309. Epub 2013 Nov 14.

Abstract

Introduction: Treatment with 1,25-dihydroxyvitamin D (1,25[OH]2 D) has several cardiovascular benefits. 1,25[OH]2 D has direct cellular effects, but its effects on the atrium are not clear. We evaluated the effects of 1,25[OH]2 D on the atrial electrophysiology and atrial fibrillation (AF).

Methods: Conventional microelectrodes were used to record action potentials (APs) and contractility in isolated rabbit left atrium (LA) tissue preparations before and after the administration of 0.01, 0.1, and 1 nM 1,25[OH]2 D with and without rapid atrial pacing (RAP) and acetylcholine (5 mM)-induced AF. Surface ECG and intracardiac electrograms were recorded before and after the intravenous administration of 4 units/kg of 1,25[OH]2 D in heart failure (HF) rabbits (4 weeks after coronary artery ligation) with RAP and acetylcholine-induced AF.

Results: 1,25[OH]2 D dose-dependently increased the AP duration in the LA, which was abolished by pretreatment with 0.1 μM ryanodine. RAP and 5 mM acetylcholine-induced fewer (64.3% vs 100%, P < 0.05) AF occurrences in the presence (n = 14) of 1,25[OH]2 D than those (n = 14) in the absence of 1,25[OH]2 D. The LA treated with 1,25[OH]2 D (n = 9) had a slower maximal AF rate (10.9 ± 2.4 Hz vs 13.3 ± 2.7 Hz, P < 0.05) than the LA (n = 14) without 1,25[OH]2 D. Moreover, 1,25[OH]2 D caused a lower AF inducible percentage (11.0 ± 1.9% vs 100 ± 0%, P < 0.001) and a shorter duration (4 ± 0.4 seconds vs 309 ± 26 seconds, P < 0.001) with a prolonged LA 90% monophasic AP duration (94.1 ± 0.2 milliseconds vs 98.5 ± 0.1 milliseconds, P < 0.05) in 5 rabbits with HF. 1,25[OH]2 D did not prolong the QT interval or 90% of the AP duration in isolated Purkinje fibers.

Conclusion: 1,25[OH]2 D has direct electromechanical effects on the LA and can prevent or terminate AF.

Keywords: acetylcholine; atrial fibrillation; heart failure; left atrium; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Animals
  • Arrhythmias, Cardiac / physiopathology
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / physiopathology
  • Biomechanical Phenomena / drug effects
  • Biomechanical Phenomena / physiology
  • Brugada Syndrome
  • Cardiac Conduction System Disease
  • Heart Atria / drug effects*
  • Heart Conduction System / abnormalities
  • Heart Conduction System / drug effects
  • Heart Conduction System / physiopathology
  • Male
  • Microelectrodes
  • Myocardial Contraction / drug effects*
  • Myocardial Contraction / physiology
  • Rabbits
  • Vitamin D / analogs & derivatives*
  • Vitamin D / pharmacology
  • Vitamin D / therapeutic use

Substances

  • Vitamin D
  • 1,25-dihydroxyvitamin D