calcitriol and Arrhythmias--Cardiac

The aim of this study was to assess the effect of combined 1,25-dihydroxyvitamin D (1,25 D) and resveratrol on cardiac arrhythmias, infarct size, and transcription of catalase, thioredoxin-1 and B-cell lymphoma 2 (Bcl-2), following myocardial ischemia-reperfusion (IR) in male rats. Ligation of coronary artery was performed in rats (n = 6 per group) without any treatment (IR group), pretreated with 0.1 μg/kg/day of 1,25 D (1,25 D + IR), 1 mg/kg/day of resveratrol (Res + IR) or a combination (1,25 D + Res + IR) for 14 days. Arrhythmias were analyzed according to the Lambeth conventions, and infarct size was measured by 2,3,5-triphenyl-2H-tetrazolium chloride staining. Expression of prosurvival genes was evaluated by real-time polymerase chain reaction. In the 1,25 D + Res + IR group the mean infarct size was 17.6 ± 3.5 %, which was significantly less than that in the IR, 1,25 D + IR, and Res + IR groups (p < 0.001). Although the single therapy of either 1,25 D or resveratrol did not change the incidence of arrhythmias significantly, a reduction in the number of ventricular ectopic beats was noted in group 1,25 D + Res + IR (179.19 ± 58.87, p < 0.001 vs IR; p < 0.05 vs Res + IR; p < 0.01 vs Vit D + IR). Combination of 1,25 D and resveratrol increased transcription of catalase by 119 ± 37 % (p < 0.001 vs IR, p < 0.01 vs Res + IR, p < 0.001 vs 1,25 D + IR). Our study showed that combination of a non-hypotensive dose of 1,25 D and resveratrol can be a novel and effective strategy for protecting against ischemia.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arrhythmias, Cardiac; Calcium; Drug Therapy, Combination; Male; Myocardial Infarction; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Reperfusion Injury; Resveratrol; RNA, Messenger; Stilbenes; Vitamin D; Vitamins

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

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Biomechanical Phenomena; Brugada Syndrome; Cardiac Conduction System Disease; Heart Atria; Heart Conduction System; Male; Microelectrodes; Myocardial Contraction; Rabbits; Vitamin D