Rate-dependent propagation of cardiac action potentials in a one-dimensional fiber

Action potential duration (APD) restitution, which relates APD to the preceding diastolic interval (DI), is a useful tool for predicting the onset of abnormal cardiac rhythms. However, it is known that different pacing protocols lead to different APD restitution curves (RCs). This phenomenon, known as APD rate-dependence, is a consequence of memory in the tissue. In addition to APD restitution, conduction velocity restitution also plays an important role in the spatiotemporal dynamics of cardiac tissue. We present new results concerning rate-dependent restitution in the velocity of propagating action potentials in a one-dimensional fiber. Our numerical simulations show that, independent of the amount of memory in the tissue, waveback velocity exhibits pronounced rate-dependence and the wavefront velocity does not. Moreover, the discrepancy between waveback velocity RCs is most significant for small DI. We provide an analytical explanation of these results, using a system of coupled maps to relate the wavefront and waveback velocities. Our calculations show that waveback velocity rate-dependence is due to APD restitution, not memory.Comment: 17 pages, 7 figure

Accepted and presented at The Design of Medical Devices Conference (DMD2016)

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is a prognostic marker for stroke, heart failure, and even death Successful ablation therapy to terminate AF requires a highly reliable technique to determine ablation sites using raw intra-atrial electrograms of AF patients. Hence, there is a clear need for a robust spatiotemporal mapping technology that can accurately identify the rotor pivot points in a patient-specific manner, which is the motivation for this research. Recently, a novel entropy-based approach was used to identify the rotor pivot point using optical mapping data from rabbit heart [4]. This approach was also used to generate 3D Shannon entropy maps for a persistent AF patient using raw intra-atrial electrograms demonstrating the feasibility to identify rotor pivot points outside the pulmonary vein (PV) region. However, challenges still remain to robustly map and more precisely confirm the exact location of rotor pivot points for AF ablation. It is known that the DF of a rotor is the same throughout the entire spatial area occupied by the rotor and therefore cannot accurately identify the rotor pivot point. This method uses a Fourier transform to calculate the DF and is therefore limited to a single frequency. In contrast, we hypothesize that the chaotic nature of the rotor at the pivot point yields various frequency components. In this work, the authors propose and demonstrate a novel multiscale frequency (MSF) approach that takes into account the contribution from various frequencies to yield valuable information regarding the rotor pivot point, thus allowing for its identification. We validate the feasibility of this technique to identify the pivot point of rotors using optical mapping data from isolated rabbit hearts with induced ventricular tachycardia (VT). Methods Novel MSF Approach. Band-pass quadrature filters are robust for estimating local multiscale information, such as the energy, phase, radial frequency, and orientation/angular frequency. The Hilbert transform operation transforms a real-valued signal to analytic signal with no negative frequencies, and its utility with the quadrature filter can yield MSF information by weighting the various frequency components. In this work, eight log-Gabor/normal filters were designed and used with a relative filter bandwidth B of 2ͱ2, one octave apart as described in Ref. where q i is the output of the ith log-Gabor filter, and q 0 is the center frequency of the first log-Gabor filter Optical Mapping Data From Isolated Rabbit Hearts. Optical Optical mapping experiments were performed with IACUC approval on isolated rabbit hearts which were put in the Langendorffperfusion system, and voltage-sensitive dye di-4-ANEPPS (5 lg/mL) was added to the perfusate. After staining, 532 nm green laser was used to illuminate the epicardial surface of the heart. Fluorescence intensity was captured with two 12-bit CCD cameras, which run at 600 frames per second with 64 Â 64 pixel resolution. VT was induced via burst pacing, and phase movies of the rotors were obtained from optical mapping recordings. The phase movies from one rabbit heart with a known pivot point were used in this work, shown in Result

Atrial GIRK Channels Mediate the Effects of Vagus Nerve Stimulation on Heart Rate Dynamics and Arrhythmogenesis

Diminished parasympathetic influence is central to the pathogenesis of cardiovascular diseases, including heart failure and hypertension. Stimulation of the vagus nerve has shown promise in treating cardiovascular disease, prompting renewed interest in understanding the signaling pathway(s) that mediate the vagal influence on cardiac physiology. Here, we evaluated the contribution of G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels to the effect of vagus nerve stimulation (VNS) on heart rate (HR), HR variability (HRV), and arrhythmogenesis in anesthetized mice. As parasympathetic fibers innervate both atria and ventricle, and GIRK channels contribute to the cholinergic impact on atrial and ventricular myocytes, we collected in vivo electrocardiogram recordings from mice lacking either atrial or ventricular GIRK channels, during VNS. VNS decreased HR and increased HRV in control mice, in a muscarinic receptor-dependent manner. This effect was preserved in mice lacking ventricular GIRK channels, but was nearly completely absent in mice lacking GIRK channels in the atria. In addition, atrial-specific ablation of GIRK channels conferred resistance to arrhythmic episodes induced by VNS. These data indicate that atrial GIRK channels are the primary mediators of the impact of VNS on HR, HRV, and arrhythmogenesis in the anesthetized mouse

A computational model of rabbit geometry and ECG: Optimizing ventricular activation sequence and APD distribution

Computational modeling of electrophysiological properties of the rabbit heart is a commonly used way to enhance and/or complement findings from classic lab work on single cell or tissue levels. Yet, thus far, there was no possibility to extend the scope to include the resulting body surface potentials as a way of validation or to investigate the effect of certain pathologies. Based on CT imaging, we developed the first openly available computational geometrical model not only of the whole heart but also the complete torso of the rabbit. Additionally, we fabricated a 32-lead ECG-vest to record body surface potential signals of the aforementioned rabbit. Based on the developed geometrical model and the measured signals, we then optimized the activation sequence of the ventricles, recreating the functionality of the Purkinje network, and we investigated different apico-basal and transmural gradients in action potential duration. Optimization of the activation sequence resulted in an average root mean square error between measured and simulated signal of 0.074 mV/ms for all leads. The best-fit T-Wave, compared to measured data (0.038 mV/ms), resulted from incorporating an action potential duration gradient from base to apex with a respective shortening of 20 ms and a transmural gradient with a shortening of 15 ms from endocardium to epicardium. By making our model and measured data openly available, we hope to give other researchers the opportunity to verify their research, as well as to create the possibility to investigate the impact of electrophysiological alterations on body surface signals for translational research

Chronic Low-Level Vagus Nerve Stimulation Improves Long-Term Survival in Salt-Sensitive Hypertensive Rats

Chronic hypertension (HTN) affects more than 1 billion people worldwide, and is associated with an increased risk of cardiovascular disease. Despite decades of promising research, effective treatment of HTN remains challenging. This work investigates vagus nerve stimulation (VNS) as a novel, device-based therapy for HTN treatment, and specifically evaluates its effects on long-term survival and HTN-associated adverse effects. HTN was induced in Dahl salt-sensitive rats using a high-salt diet, and the rats were randomly divided into two groups: VNS (n = 9) and Sham (n = 8), which were implanted with functional or non-functional VNS stimulators, respectively. Acute and chronic effects of VNS therapy were evaluated through continuous monitoring of blood pressure (BP) and ECG via telemetry devices. Autonomic tone was quantified using heart rate (HR), HR variability (HRV) and baroreflex sensitivity (BRS) analysis. Structural cardiac changes were quantified through gross morphology and histology studies. VNS significantly improved the long-term survival of hypertensive rats, increasing median event-free survival by 78% in comparison to Sham rats. Acutely, VNS improved autonomic balance by significantly increasing HRV during stimulation, which may lead to beneficial chronic effects of VNS therapy. Chronic VNS therapy slowed the progression of HTN through an attenuation of SBP and by preserving HRV. Finally, VNS significantly altered cardiac structure, increasing heart weight, but did not alter the amount of fibrosis in the hypertensive hearts. These results suggest that VNS has the potential to improve outcomes in subjects with severe HTN

Trends in the epidemiology of diabetic retinopathy in Russian Federation according to the Federal Diabetes Register (2013–2016)

Background: Diabetic retinopathy (DR) is one of the most common causes of blindness in patients with diabetes mellitus (DM) that is why its necessary to study the epidemiological characteristics of this complication. Aims: The aim of the study was to evaluate the epidemiological characteristics of DR and blindness in adult patients with type 1 (T1) and 2 (T2) diabetes in Russian Federation (RF) for period 201316years. Materials and methods: Database of Federal Diabetes register, 81st regions included in the online register. Indicators were estimated per 10,000 adult DM patients (18years). Results: In 2016 the DR prevalence in RF was T1 38,3%, T2 15,0%, with marked interregional differences: 2,666,1%, 1,146,4%, respectively. The DR prevalence within 20132016 years was: T1 3830,93805,6; T2 1586,01497,0. Trend of new DR cases/per year increased: T1 153,2187,8; T2 99,7114,9. The structure of new cases of DR in 2016: non-proliferative stage (T1 71,4%, T2 80,3%), pre-proliferative stage 16,4%, 13,8%, proliferative 12,1%, 5,8%, terminal 0,2%, 0,1%, respectively, these data indicated the earlier detection of DR. The mean age of DR diagnosis increased: T1 by 1,2 years, T2 by 2,6. The average DM duration of DR determine increased T1 9,613,1 years, T2 6,09,1. The prevalence of blindness tends to decrease: T1 92,390,8; T2 15,415,2/10.000 DM adults. The amount of new cases of blindness/per year increased: T1 4,34,6; T2 1,21,4. The mean age of blindness increased: T1 39,141,6 years, T2 64,467,4; the mean duration of diabetes before blindness occur (from the time of DM diagnosis) increased: T1 20,221,2 years, in T2 10,711,3. We observed growth of DR treatment (laser surgery, vitrectomy, anti-VEGF medication) but the frequency of use in T2 patients is about 2 times less than in T1. Conclusions: There was a decrease in the overall incidence of eye damage in diabetes (DR and blindness) in the analyzed period in RF. DR and blindness develops at advanced age and with a longer duration of diabetes. As the main directions of eye care development in diabetes it is necessary to standardize primary care in the regions, to unify the examination algorithms and methods of early diagnostic, to increase the continuity and interaction of endocrinologists and ophthalmologists in managing patients with diabetes in order to prevent the development of new cases of vision loss