Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with significant morbidity and mortality. The autonomic nervous system (ANS) plays an important role in the initiation and development of AF, causing alterations in atrial structure and electrophysiological defects. The intrinsic ANS of the heart consists of multiple ganglionated plexi (GP), commonly nestled in epicardial fat pads. These GPs contain both parasympathetic and sympathetic afferent and efferent neuronal circuits that control the electrophysiological properties of the myocardium. Pulmonary vein isolation and other cardiac catheter ablation targets including GP ablation can disrupt the fibers connecting GPs or directly damage the GPs, mediating the benefits of the ablation procedure. Ablation of GPs has been evaluated over the past decade as an adjunctive procedure for the treatment of patients suffering from AF. The success rate of GP ablation is strongly associated with specific ablation sites, surgical techniques, localization techniques, method of access and the incorporation of additional interventions. In this review, we present the current data on the clinical utility of GP ablation and its significance in AF elimination and the restoration of normal sinus rhythm in humans.

Aims: Irreversible electroporation is an ablation technique being adapted for the treatment of atrial fibrillation. Currently, there are many differences reported in the in vitro and pre-clinical literature for the effective voltage threshold for ablation. The aim of this study is a direct comparison of different cell types within the cardiovascular system and identification of optimal voltage thresholds for selective cell ablation. Methods: Monophasic voltage pulses were delivered in a cuvette suspension model. Cell viability and live–dead measurements of three different neuronal lines, cardiomyocytes, and cardiac fibroblasts were assessed under different voltage conditions. The immediate effects of voltage and the evolution of cell death was measured at three different time points post ablation. Results: All neuronal and atrial cardiomyocyte lines showed cell viability of less than 20% at an electric field of 1000 V/cm when at least 30 pulses were applied with no significant difference amongst them. In contrast, cardiac fibroblasts showed an optimal threshold at 1250 V/cm with a minimum of 50 pulses. Cell death overtime showed an immediate or delayed cell death with a proportion of cell membranes re-sealing after three hours but no significant difference was observed between treatments after 24 h. Conclusions: The present data suggest that understanding the optimal threshold of irreversible electroporation is vital for achieving a safe ablation modality without any side-effect in nearby cells. Moreover, the evolution of cell death post electroporation is key to obtaining a full understanding of the effects of IRE and selection of an optimal ablation threshold.

Parkinson’s Disease (PD) is a chronic neurodegenerative disorder characterized by motor and non-motor symptoms, among which are bradykinesia, rigidity, tremor as well as mental symptoms such as dementia. The underlying cause of Parkinson disease is degeneration of dopaminergic neurons. It has been challenging to develop an efficient animal model to accurately represent the complex phenotypes found with PD. However, it has become possible to recapitulate the myriad of phenotypes underlying the PD pathology by using human induced pluripotent stem cell (iPSC) technology. Patient-specific iPSC-derived dopaminergic neurons are available and present an opportunity to study many aspects of the PD phenotypes in a dish. In this review, we report the available data on iPSC-derived neurons derived from PD patients with identified gene mutations. Specifically, we will report on the key phenotypes of the generated iPSC-derived neurons from PD patients with different genetic background. Furthermore, we discuss the relationship these cellular phenotypes have to PD pathology and future challenges and prospects for iPSC modelling and understanding of the pathogenesis of PD.

Targeted cellular ablation is being increasingly used in the treatment of arrhythmias and structural heart disease. Catheter-based ablation for atrial fibrillation (AF) is considered a safe and effective approach for patients who are medication refractory. Electroporation (EPo) employs electrical energy to disrupt cell membranes which has a minimally thermal effect. The nanopores that arise from EPo can be temporary or permanent. Reversible electroporation is transitory in nature and cell viability is maintained, whereas irreversible electroporation causes permanent pore formation, leading to loss of cellular homeostasis and cell death. Several studies report that EPo displays a degree of specificity in terms of the lethal threshold required to induce cell death in different tissues. However, significantly more research is required to scope the profile of EPo thresholds for specific cell types within complex tissues. Irreversible electroporation (IRE) as an ablative approach appears to overcome the significant negative effects associated with thermal based techniques, particularly collateral damage to surrounding structures. With further fine-tuning of parameters and longer and larger clinical trials, EPo may lead the way of adapting a safer and efficient ablation modality for the treatment of persistent AF.

Background: Irreversible electroporation has emerged as a new modality to overcome issues associated with other energy sources for cardiac ablation. Strong evidence on the optimal, effective, and selective voltage threshold is lacking for both in vitro and preclinical in vivo studies. The aim of this study is to examine the optimal threshold for selective cell ablation on cardiac associated cell types.Methods: Conventional monophasic and biphasic pulses of different field strength were delivered in a monolayer culture system of cardiomyocytes, neurons, and adipocytes. The dynamics of cell death mechanisms were examined at different time points.Results: Neurons exhibit higher susceptibility to electroporation and cell death at higher field strength of 1250 V/cm in comparison to cardiomyocytes. Cardiac adipocytes showed lower susceptibility to electroporation in comparison to other cell types. A significant proportion of cardiomyocytes recovered after 24 h postelectroporation, while neuronal cell death remained consistent but with a significant delayed cell death at a higher voltage threshold. Caspase 3/7 activity was observed in both cardiomyocytes and neurons, with a higher level of activity in cardiomyocytes in response to electroporation. Biphasic and monophasic pulses showed no significant difference in both cell types, and significantly lower cell death in neurons when inter pulse interval was reduced.Conclusions: This study presents important findings on the differences in the susceptibility of neurons and cardiomyocytes to irreversible electroporation. Cell type alone yielded selective and different dynamics in terms of the evolution and signaling mechanism of cell death in response to electroporation.

Currently, 1% of the population of the Western world suffers from venous leg ulcers as a result of chronic venous insufficiency. Current treatment involves the use of moist wound healing, compression bandages, and intermittent pneumatic compression. Neuromuscular electrical stimulation is a novel potential new therapeutic method for the promotion of increased lower limb hemodynamics. The aim of this study was to measure the hemodynamic changes in the lower limb with the use of two neuromuscular electrical stimulation devices. Twelve healthy volunteers received two neuromuscular stimulation device interventions. The Geko^TM and National University of Ireland (NUI) Galway neuromuscular electrical stimulation devices were randomized between dominant and non-dominant legs. Hemodynamic measurements of peak venous velocity (cm/s), the time average mean velocity (TAMEAN) (cm/s), and ejected volume (mL) of blood were recorded. Peak venous velocity was significantly increased by the Geko^TM and the NUI Galway device compared to baseline blood flow (p < 0.0001), while only the voluntary contraction produced significant increases in TAMEAN and ejected volume (both p < 0.05). Neuromuscular muscular electrical stimulation can produce adequate increases in lower limb hemodynamics sufficient to prevent venous stasis. Greater use of neuromuscular stimulation devices could be considered in the treatment of conditions related to chronic venous insufficiency but requires further research.