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

Electromechanical Effects of 1,25-Dihydroxyvitamin D on the LA Introduction Treatment with 1,25-dihydroxyvitamin D (1,25[OH]2D) has several cardiovascular benefits. 1,25[OH]2D has direct cellular effects, but its effects on the atrium are not clear. We evaluated the effects of 1,25[OH]2D 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] 2D 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]2D in heart failure (HF) rabbits (4 weeks after coronary artery ligation) with RAP and acetylcholine-induced AF. Results 1,25[OH]2D 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]2D than those (n = 14) in the absence of 1,25[OH]2D. The LA treated with 1,25[OH]2D (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]2D. Moreover, 1,25[OH]2D 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]2D did not prolong the QT interval or 90% of the AP duration in isolated Purkinje fibers. Conclusion 1,25[OH]2D has direct electromechanical effects on the LA and can prevent or terminate AF.