Development of a rapid and economic in vivo electrocardiogram platform for cardiovascular drug assay and electrophysiology research in adult zebrafish.

Zebrafish is a popular and favorable model organism for cardiovascular research, with an increasing number of studies implementing functional assays in the adult stage. For example, the application of electrocardiography (ECG) in adult zebrafish has emerged as an important tool for cardiac pathophysiology, toxicity, and chemical screen studies. However, few laboratories are able to perform such functional analyses due to the high cost and limited availability of a convenient in vivo ECG recording system. In this study, an inexpensive ECG recording platform and operation protocol that has been optimized for adult zebrafish ECG research was developed. The core hardware includes integration of a ready-to-use portable ECG kit with a set of custom-made needle electrode probes. A combined anesthetic formula of MS-222 and isoflurane was first tested to determine the optimal assay conditions to minimize the interference to zebrafish cardiac physiology under sedation. For demonstration, we treated wild-type zebrafish with different pharmacological agents known to affect cardiac rhythms in humans. Conserved electrophysiological responses to these drugs were induced in adult zebrafish and recorded in real time. This economic ECG platform has the potential to facilitate teaching and training in cardiac electrophysiology with adult zebrafish and to promote future translational applications in cardiovascular medicine.

Electrophysiological Assessment of Murine Atria with High-Resolution Optical Mapping.

Recent genome-wide association studies targeting atrial fibrillation (AF) have indicated a strong association between the genotype and electrophysiological phenotype in the atria. That encourages us to utilize a genetically-engineered mouse model to elucidate the mechanism of AF. However, it is difficult to evaluate the electrophysiological properties in murine atria due to their small size. This protocol describes the electrophysiological evaluation of atria using an optical mapping system with a high temporal and spatial resolution in Langendorff perfused murine hearts. The optical mapping system is assembled with dual high-speed complementary metal oxide semiconductor cameras and high magnification objective lenses, to detect the fluorescence of a voltage-sensitive dye and Ca2+ indicator. To focus on the assessment of murine atria, optical mapping is performed with an area of 2 mm × 2 mm or 10 mm x 10 mm, with a 100 × 100 resolution (20 µm/pixel or 100 µm/pixel) and sampling rate of up to 10 kHz (0.1 ms) at maximum. A 1-French size quadripolar electrode pacing catheter is placed into the right atrium through the superior vena cava avoiding any mechanical damage to the atrium, and pacing stimulation is delivered through the catheter. An electrophysiological study is performed with programmed stimulation including constant pacing, burst pacing, and up to triple extrastimuli pacing. Under a spontaneous or pacing rhythm, the optical mapping recorded the action potential duration, activation map, conduction velocity, and Ca2+ transient individually in the right and left atria. In addition, the programmed stimulation also determines the inducibility of atrial tachyarrhythmias. Precise activation mapping is performed to identify the propagation of the excitation in the atrium during an induced atrial tachyarrhythmia. Optical mapping with a specialized setting enables a thorough electrophysiological evaluation of the atrium in murine pathological models.

Análise crítica dos estudos com os novos anticoagulantes / Critical anlysis of studes on the novel anticoagulantes

Os eventos tromboembólicos são complicações significativas da fibrilação atrial (FA) e podem ser prevenidos com a anticoagulação oral plena. A varfarina reduz em 64% o risco de tromboembolismo, no entanto, a dificuldade no seu manejo clínico motivou a busca por novos anticoagulantes orais (NOACs). Os NOACs inibem especificamente um único fator na cascata da coagulação, têm meia vida curta, efeito previsível e estável, dispensam monitorização e interagem pouco com alimentos e medicamentos.Os estudos RE-LY, ROCKET-AF, ARISTOTLE e ENGAGE AFTIMI48 compararam a varfarina com a dabigratana, rivaroxabana,apixabana e edoxabana, respectivamente, e evidenciaram que os NOACS são equivalentes (dabigatrana 110 mg, rivaroxabana,edoxabana) ou superiores (dabigatrana 150 mg, apixabana) à varfarina na prevenção de tromboembolismo sistêmico ou AVC em pacientes com FA não valvar. Ademais, apresentam índices de hemorragias intracranianas substancialmente menores do quea varfarina. Já a apixabana foi superior à aspirina na prevençãode AVC, com os mesmos índices de sangramento. Os NOACs não devem ser usados em gestantes, crianças, e em pacientes com estenose mitral significativa, próteses valvares ou função renal muito deprimida. Porém, podem ser usados nos cenários de cardioversão e ablação da FA. Ainda não há estudos comparativos entre os diversos NOACs, nem consenso de quando recomendara troca da varfarina em pacientes com RNI estável. Cerca de 50%dos pacientes com FA e indicação de anticoagulação não recebem terapia anticoagulante. Portanto, com advento dos NOACs, a expectativa é reduzir essa parcela, diminuindo a incidência de fenômenos tromboembólicos na FA.

Thromboembolic events are important complications of atrialfibrillation (AF) and can be prevented by oral anticoagulation.Warfarin reduces by 64% the risk of thromboembolism,however, the difficulties in its clinical management promptedthe search for novel oral anticoagulants (NOACs). The NOACsspecifically inhibit a single factor in the coagulation cascade,have a short half-life, predictable and stable effect, do not requiremonitoring and have minor interactions with food and drugs.The RE-LY, ROCKET-AF, ARISTOTLE and ENGAGE AFTIMI48 trials compared warfarin to dabigatran, rivaroxaban,apixaban and edoxaban, respectively, and showed that NOACSare equivalent (110 mg dabigatran, rivaroxaban, edoxaban) orsuperior (dabigatran 150 mg, apixaban) to warfarin in preventingstroke or systemic embolism in patients with nonvalvular AF.Furthermore, they are associated with substantially lower levelsof intracranial bleeding than warfarin. Apixaban was superiorto aspirin in preventing strokes, with the same rate of bleeding.The NOACs should not be used in pregnant women, children,and patients with significant mitral stenosis, prosthetic valvesor impaired renal function. However, these novel drugs can beused in the scenarios of cardioversion and AF ablation. Thereare no studies comparing individual NOACs or consensus aboutswitching patients on warfarin with stable INR. Approximately50% of patients with AF and recommendation for anticoagulationdo not receive anticoagulant therapy. Therefore, with the adventof NOACs, the expectation is to improve this figure, ultimatelydecreasing the incidence of thromboembolic events in AF.

Simulations of complex and microscopic models of cardiac electrophysiology powered by multi-GPU platforms.

Key aspects of cardiac electrophysiology, such as slow conduction, conduction block, and saltatory effects have been the research topic of many studies since they are strongly related to cardiac arrhythmia, reentry, fibrillation, or defibrillation. However, to reproduce these phenomena the numerical models need to use subcellular discretization for the solution of the PDEs and nonuniform, heterogeneous tissue electric conductivity. Due to the high computational costs of simulations that reproduce the fine microstructure of cardiac tissue, previous studies have considered tissue experiments of small or moderate sizes and used simple cardiac cell models. In this paper, we develop a cardiac electrophysiology model that captures the microstructure of cardiac tissue by using a very fine spatial discretization (8 µm) and uses a very modern and complex cell model based on Markov chains for the characterization of ion channel's structure and dynamics. To cope with the computational challenges, the model was parallelized using a hybrid approach: cluster computing and GPGPUs (general-purpose computing on graphics processing units). Our parallel implementation of this model using a multi-GPU platform was able to reduce the execution times of the simulations from more than 6 days (on a single processor) to 21 minutes (on a small 8-node cluster equipped with 16 GPUs, i.e., 2 GPUs per node).

[The assessment of reactions of polygraphic parameters at HRV-biofeedback training in adolescents with different variants of cardiac autonomic nervous system tone].

There is examine a character of change of brain bioelectric activity and polygraphic indicators at sessions of biofeedback by heart rhythm variability parameters (HRV-biofeedback) in 15-17 years adolescents who have different variants of cardiac autonomic nervous system tone. It is taped, that adolescents with cardiac balanced tone have more intensive optimization of functional brain activity in comparison with adolescents who have cardiac sympathetic tone - increase on alpha-activity and theta-activity depression in electroencephalogram structure. There were optimization of neurodynamic processes and most expressed stabilization of the hemodynamics indicators in adolescents with cardiac sympathetic tone after HRV-biofeedback training.

Health technology assessment on reprocessing single-use catheters for cardiac electrophysiology: results of a three-years study.

The study aims to define the technical, ethical, juridical and economic issues involved in the assessment of a reprocessing policy for single-use interventional cardiac devices (SUDs). The feasibility of reprocessing was evaluated for cardiac electrophysiology catheters by comparing the chemical, physical and functional properties of new and reprocessed devices. The issue of hygiene was addressed by developing microbiological tests for the quantification of bioburden, sterility and pyrogenic load. The results of more than 1500 tests, conducted on 531 catheters, suggested a precautionary number of regenerations of five cycles. The ethical aspects were reviewed and the European juridical framework was assessed, revealing a need for harmonization. Applying a specific economic model, potential savings were calculated for a representative cardiology department and estimated at national and European level. Potential savings of 41.2% and 32.9% were calculated for diagnostic and ablation catheters, respectively. Safe and effective reprocessing of SUDs could be pursued if quality control processes and certified procedures are met. A reprocessing policy in EP laboratory could lead to savings of about 27,250 euros per 100,000 population, but the economic benefits are strongly dependent on the maximum number of regenerations and the regeneration rate.