dimethylarginine and Atrial-Fibrillation

It was our aim to study the levels of L-arginine, the substrate for nitric oxide and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and their relation to the maintenance of sinus rhythm after electrical cardioversion for atrial fibrillation (AF), as well as the effects of angiotensin receptor blockade on these variables.. In a double-blind, placebo-controlled study, patients with persistent AF were randomised to receive candesartan 8 mg once daily or placebo for 3-6 weeks before and candesartan 16 mg once daily or placebo for 6 months after cardioversion. As part of this study, plasma levels of L-arginine and ADMA were measured at baseline and at the end of the study.. Baseline levels of L-arginine, ADMA and the L-arginine/ADMA ratio were not predictive of rhythm outcome, and their levels were not influenced by treatment with candesartan. However, the L-arginine/ADMA ratio increased in patients who remained in sinus rhythm (n = 37) for 6 months when compared with patients with AF recurrence (n = 61; p = 0.008).. Neither L-arginine nor ADMA or their ratio were predictive of rhythm outcome after cardioversion, and they were not influenced by treatment with candesartan. However, the L-arginine/ADMA ratio increased in patients still in sinus rhythm 6 months after cardioversion.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Arginine; Atrial Fibrillation; Benzimidazoles; Biphenyl Compounds; Combined Modality Therapy; Double-Blind Method; Electric Countershock; Female; Humans; Male; Middle Aged; Recurrence; Tetrazoles; Time Factors

High levels of asymmetric dimethylarginine (ADMA) are associated with an increased risk of early recurrence of atrial fibrillation (AF) after electrical cardioversion. We aimed to investigate the effects of rosuvastatin on serum ADMA levels and early recurrence of AF following successful electrical cardioversion.. A total of 64 patients with persistent AF, but without known heart disease, who underwent elective electrical cardioversion were randomized to the rosuvastatin (group I, n = 32) and control (group II, n = 32) groups. The end point was the recurrence of AF during the 3 months of follow-up.. The baseline ADMA levels were not different between the two groups. At the end of follow-up, serum ADMA levels in group I decreased compared with the baseline levels, whereas no significant change occurred in group II. During the follow-up, five patients in group I (15.6%) and 13 in group II (40.6%) had AF recurrence (P < 0.05, log-rank test). With the Cox proportional model, the predictors of recurrence included age > or =65 years, left atrial diameter >45 mm, and baseline ADMA levels > or =2.0 micromol/l. Rosuvastatin was associated with a reduced risk of AF recurrence (relative risk 0.35, 95% confidence interval 0.12-0.96, P < 0.05).. Rosuvastatin decreased the early recurrence of AF following successful electrical cardioversion with reduced ADMA levels.

Topics: Aged; Arginine; Atrial Fibrillation; Electric Countershock; Female; Fluorobenzenes; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Pyrimidines; Recurrence; Rosuvastatin Calcium; Sulfonamides

Atrial fibrillation (AF) is responsible for some thromboembolic events. Asymmetrical dimethylarginine(ADMA) increases in atrial fibrillation(AF) animals with dysfunction of endothelium, but its role in pro-thrombotic state of AF was unknown. The aim of our study was to explore the role of ADMA in predicting the pro-thrombotic state in AF and to reveal its mechanism.. One hundred and thirty-eight patients in the First Affiliated Hospital, Sun Yat-sen University, from 2010 to 2012, were enrolled (persistent atrial fibrillation group, PAF, n=80; paroxysmal atrial fibrillation group, Paf, n=30; sinus rhythm, SR, n=28). Plasma ADMA levels were detected by ELISA-kits. CHADS2 and CHA2DS2-VASc scores were estimated for each patient.14 Beagles (pacing group, n=8; sham group, n=6) were subjected to rapid atrial pacing (RAP). ADMA level was detected after 4 weeks of RAP.. ADMA level was elevated significantly in patients with atrial fibrillation especially in patients with persistent atrial fibrillation, and showed a significant linear correlation to CHADS2 and CHA2DS2-VASc score. With ADMA, ROC area under the curve was 0.865 in CHADS2 score ≥2 and was 0.959 in CHA2DS2-VASc score ≥2 (P<0.001 respectively). After 4 weeks of RAP, ADMA level was elevated compared to sham group and before operation. ADMA showed a linear correlation with atrial fibrillation susceptibility(r=0.686, P=0.007).. ADMA levels are elevated both in AF patients and RAP beagles. ADMA correlates with stroke risk concerning with CHADS2/CHA2DS2-VASc score. ADMA may become a new biomarker for predicting pro-thrombotic risk in AF.

Topics: Arginine; Atrial Fibrillation; Cardiovascular Diseases; Heart Atria; Humans; Stereoisomerism; Thrombosis

Left atrial (LA) remodeling associated with atrial fibrillation (AF) is known to be related to inflammation and collagen turnover. We investigated the changes in the biomarkers of inflammation and collagen turnover in relation to LA reverse remodeling during the 1st year after AF ablation.. Biomarkers of inflammation [high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6)] and collagen turnover [matrix metalloproteinase-2 (MMP-2), tissue inhibitor of MMP-2 (TIMP-2), transforming growth factor beta 1 (TGF-β1)], as well as asymmetric dimethylarginine (ADMA) and adiponectin levels were measured, and echocardiographic measurements were obtained before and 3, 6, and 12 months after ablation in 60 AF patients (49 males; age, 57.6 ± 10.9 years).. During a 12.1 (11.5-12.9)-month follow-up period, AF recurred in 29 patients (48 %). Neither the LA volume (LAV) nor the left ventricular ejection fraction (LVEF) changed significantly during the 1st year in this group, but the LAV decreased significantly, and the LVEF increased significantly in the nonrecurrence group. The hs-CRP and IL-6 decreased after ablation but returned near to baseline levels in both groups by 12 months. The MMP-2 remained increased during the 1st year in both groups, whereas the TIMP-2 increased markedly in the nonrecurrence group but did not change substantially in the recurrence group. The TGF-β1 increased in both groups, but the change was less pronounced in the recurrence group. The ADMA and adiponectin levels did not change substantially in either group.. Despite reverse remodeling, the inflammation and collagen turnover biomarker levels are quite progressive during the 1st year after ablation and may explain the late AF recurrence.

Topics: Adiponectin; Arginine; Atrial Fibrillation; Biomarkers; C-Reactive Protein; Catheter Ablation; Diagnostic Imaging; Echocardiography; Electrocardiography; Extracellular Matrix; Female; Humans; Inflammation; Interleukin-6; Male; Matrix Metalloproteinase 2; Middle Aged; Predictive Value of Tests; Recurrence; Tissue Inhibitor of Metalloproteinase-2; Transforming Growth Factor beta; Treatment Outcome

Circulating asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is increased in atrial fibrillation (AF). The purpose of this study was to investigate the effects of rosuvastatin on serum ADMA levels and atrial structural remodeling in AF dogs induced by chronic rapid atrial pacing.. Twenty dogs were randomly divided into the sham-operated (n=6), control (n=7), or rosuvastatin (n=7) groups. Sustained AF was induced by rapid pacing of the right atrium at 400 beats per minute for 6 weeks. Rosuvastatin was administered orally (1 mg/kg d) for 3 days before rapid pacing and was continued for 6 weeks. Transthoracic and transesophageal echocardiography were performed to detect left atrial structure and function. Serum levels of nitric oxide and ADMA were measured. Interstitial fibrosis and cardiomyocyte apoptosis in the atria were also identified.. After 6 weeks, compared with the control group, dramatic smaller left atrium and left atrial appendage volumes and higher atrial contractile function were observed in the rosuvastatin group. Serum nitric oxide concentration was increased, whereas ADMA was decreased in the rosuvastatin group compared with the control group. The percentages of interstitial fibrosis and atrial apoptosis in the control group were significantly higher than those in the sham-operated group, and rosuvastatin attenuated these changes induced by atrial rapid pacing.. A short course of rosuvastatin treatment decreased apoptosis and prevented atrial structural remodeling in association with a decrease in ADMA levels in AF dogs.

Topics: Animals; Apoptosis; Arginine; Atrial Fibrillation; Atrial Function, Left; Dogs; Echocardiography, Transesophageal; Female; Fluorobenzenes; Heart; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Myocardium; Nitric Oxide; Pyrimidines; Rosuvastatin Calcium; Sulfonamides

Atrial fibrillation (AF) may cause thrombus formation in the left atrial appendage (LAA). Thrombus formation is associated with LAA endocardial dysfunction. Because asymmetrical dimethylarginine (ADMA) can cause endothelial dysfunction by decreasing nitric oxide (NO) formation, we investigated plasma ADMA and nitrite/nitrate (NO(X)) levels and myocardial dimethylarginine dimethylaminohydrolase-2 (DDAH-2), protein arginine methyltransferase-1 (PRMT-1), and endothelial NO synthase (eNOS) protein contents from AF dogs. The results displayed that plasma ADMA level significantly increased, and plasma NO(X) concentration significantly decreased. Compared with normal heart, DDAH-2 expression was unchanged in the fibrillating atria. However, the DDAH activity was significantly decreased in the fibrillating atria. PRMT-1 expression significantly increased in the LAA and in the left atrium (LA). ENOS expression significantly decreased in the LA. ENOS and PRMT-1 expressions were unchanged in the right atria. Our results suggested that the DDAH-PRMT-ADMA system maybe play a pivotal role in regulating endothelial function in AF.

Topics: Amidohydrolases; Animals; Arginine; Atrial Fibrillation; Disease Models, Animal; Dogs; Down-Regulation; Endothelium; Female; Male; Myocardium; Nitric Oxide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Protein-Arginine N-Methyltransferases; Thrombosis; Up-Regulation