Nitro-fatty acids suppress ischemic ventricular arrhythmias by preserving calcium homeostasis.

Nitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. Herein, we demonstrate that pretreatment of mice with 9- and 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO2-OA treatment of isolated cardiomyocytes lowered the number of spontaneous contractions upon adrenergic isoproterenol stimulation and nearly abolished ryanodine receptor type 2 (RyR2)-dependent sarcoplasmic Ca2+ leak. NO2-OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO2-OA might be a novel pharmacological option for the prevention of VT development.

Active Atrial Function and Atrial Scar Burden After Multiple Catheter Ablations of Persistent Atrial Fibrillation.

BACKGROUND: Extensive and repeated substrate modification (SM) is frequently performed as an ablation strategy in persistent atrial fibrillation (persAF). The effect of these extended ablation strategies on atrial function has not been investigated sufficiently so far. The purpose was to assess atrial function by cardiac magnetic resonance (CMR) and its association with left atrial (LA) scar burden by electroanatomical voltage-mapping after multiple persAF ablation procedures. METHODS: We included 16 persAF patients who had ≥2 SM procedures and a control group (CG) of 21 persAF patients without prior ablation. CMR was performed in sinus rhythm at least 4 weeks after the last cardioversion. Active left and right (RA) atrial emptying fractions (AEF) as well as peak active left atrial appendage (LAA) emptying velocities were obtained by CMR flow measurements. Furthermore, LA scar burden was quantified on electroanatomical voltage maps by the portion of points with local voltage amplitude <0.2 mV. RESULTS: We found median LA-AEF to be lower (13 [9-22] vs 32 [26-36] %, P < 0.001) and median LA scar burden to be higher (40 [20-68] vs nine [3-18] %, P < 0.05) in the SM group compared with the CG. Furthermore, a significant correlation was found between mean LA voltage and LA-AEF (r2 = 0.62, P < 0.001). No significant differences were detected with respect to median RA-AEF (41 [28-48] vs 47 [35-50] %, P = 0.43) and median peak LAA emptying velocities (30 [16-40] vs 17 [13-28] cm/s, P = 0.07). CONCLUSIONS: Active LA function is preserved but significantly impaired and associated with ablation-related LA scar burden after multiple extensive persAF ablations.

Nitroalkylation--a redox sensitive signaling pathway.

Redox-sensitive posttranslational modification emerged as important signaling mechanisms. Besides other posttranslational modifications nitroalkylation by nitrated fatty acids mediate favorable anti-inflammatory effects. This review gives an overview of the generation and the reactivity of nitrated fatty acids. Additionally, it provides insights into the so far described pathways regulated by nitrated fatty acids. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation.