Autonomic Regulation and Ventricular Arrhythmias.

Autonomic nervous system (ANS) has a crucial role of regulating cardiac function in the physiological state and contributes to the pathogenesis of arrhythmias in the diseased state. The cardiac neuraxis consists of multiple feedback loops consisting of efferent and afferent limbs, mediating neurotransmission to and from the heart. Efferent parasympathetic neurotransmission is mediated by the vagus nerve, while paravertebral sympathetic ganglia relay efferent sympathetic neurotransmission to the heart. The association between autonomic activity and ventricular arrhythmias (VAs) has been studied extensively in both experimental models and humans. Efferent parasympathetic activity is felt to be antiarrhythmic, while the activation of efferent sympathetic signals is proarrhythmic. The cardiac neuraxis undergoes remodeling and becomes dysfunctional in the setting of myocardial infarction (MI), chronic cardiomyopathy (CMY), and structural heat disease. Altered ANS function has been shown to initiate and/or maintain VAs via various mechanisms. Interventions targeting the ANS have been used clinically to treat VAs, particularly in patients with hereditary heart rhythm disorders and structurally abnormal hearts. Clinical applications of cardiac neuraxial modulation at the level of spinal cord, stellate ganglion, and peripheral sympathetic and vagus nerve are being developed. In this review, the anatomy of cardiac autonomic innervation, the association between autonomic activity and ventricular arrhythmogenesis, and clinical applications of neuraxial modulation in the treatment of VAs are discussed.

Efficacy of Stellate Ganglion Blockade in Managing Electrical Storm: A Systematic Review.

BACKGROUND: The efficacy of percutaneous stellate ganglion block (SGB) for managing electrical storm (ES) is not well understood. OBJECTIVE: To characterize the efficacy of SGB as a treatment for ES. METHODS: We conducted literature searches using PubMed/Medline and Google Scholar, for mixed combinations of terms including "stellate ganglion block", *ganglion block (ade)", "sympathetic block (ade)" and "arrhythmia", "ventricular arrhythmia (VA)" or "tachycardia" (VT), "ventricular fibrillation" (VF), "electrical storm". Inclusion criteria were presentation with guideline-defined ES and treatment with SGB. Exclusion criteria: presentation with any supraventricular arrhythmia, VA without ES, or surgical sympathectomy. Studies lacking basic demographic data, arrhythmia description, and outcomes were excluded. RESULTS: Of 3,374 publications reviewed, 38 patients from 23 studies met study criteria (52 ± 19.1 years, 11 F, 17 with ischemic cardiomyopathy). Anti-arrhythmics were used in all patients. Mean Left ventricular ejection fraction was 31 ± 10%. ES was triggered by acute myocardial infarction in 15 patients and QT prolongation in 7 patients. The most common local anesthetic used for SGB was bupivacaine (0.25-0.5%). SGB resulted in a significant decrease in VA burden (12.4±8.8 vs. 1.04±2.12 episodes/day, p< 0.001) and number of external and ICD shocks (10.0±9.1 vs. 0.05±0.22 shocks/day, p< 0.01). Following SGB, 80.6% of patients survived to discharge. CONCLUSION: SGB is an effective acute treatment for ES. However, larger prospective randomized studies are needed to better understand the role of SGB in ES and other VAs.

AID-expressing germinal center B cells cluster normally within lymph node follicles in the absence of FDC-M1+ CD35+ follicular dendritic cells but dissipate prematurely.

Upon activation with T-dependent Ag, B cells enter germinal centers (GC) and upregulate activation-induced deaminase (AID). AID(+) GC B cells then undergo class-switch recombination and somatic hypermutation. Follicular dendritic cells (FDC) are stromal cells that underpin GC and require constitutive signaling through the lymphotoxin (LT) ß receptor to be maintained in a fully mature, differentiated state. Although it was shown that FDC can be dispensable for the generation of affinity-matured Ab, in the absence of FDC it is unclear where AID expression occurs. In a mouse model that lacks mature FDC, as well as other LT-sensitive cells, we show that clusters of AID(+)PNA(+)GL7(+) Ag-specific GC B cells form within the B cell follicles of draining lymph nodes, suggesting that FDC are not strictly required for GC formation. However, later in the primary response, FDC-less GC dissipated prematurely, correlating with impaired affinity maturation. We examined whether GC dissipation was due to a lack of FDC or other LTß receptor-dependent accessory cells and found that, in response to nonreplicating protein Ag, FDC proved to be more critical for long-term GC maintenance. Our study provides a spatial-temporal analysis of Ag-specific B cell activation and AID expression in the context of a peripheral lymph node that lacks FDC-M1(+) CD35(+) FDC and other LT-sensitive cell types, and reveals that FDC are not strictly required for the induction of AID within an organized GC-like environment.