Higher Conduction Velocity Research Articles

Normative values and factors affecting saphenous nerve responses in a south Asian population: a cross-sectional neurophysiological study at a tertiary care hospital in Pakistan

BackgroundThe saphenous nerve, a sensory branch of the femoral nerve, is not commonly included in routine lower extremity nerve conduction studies due to a high frequency of non-recordable responses in healthy subjects. However, saphenous nerve conduction studies are sometimes utilized for the diagnostic assessment of isolated lumbosacral plexus, femoral, or saphenous mononeuropathies. Our study aims to determine normative saphenous nerve response values in a healthy Pakistani population and to investigate their associations with patient body mass index, age, and gender.MethodsThis cross-sectional descriptive study was undertaken over a 3‑month period (May to July 2021) at a neurophysiology department of a tertiary care center in Pakistan. Healthy subjects underwent neurological examination, anthropometric measurements, and bilateral SN nerve conduction studies, with recording of peak-latency, peak-to-peak amplitude and conduction velocity. Statistical analyses and linear regression were conducted to evaluate associations between nerve conduction study variables and patient characteristics. Statistical analyses were also run to assess patient characteristics affecting recordability of saphenous nerve responses. A p-value < 0.05 was considered statistically significant.ResultsAmong 117 subjects, 79.5% (n = 93) had recordable saphenous nerve responses. Median peak-latency, amplitude, and conduction velocity were 3.2 (3.0-3.3) m/s, 7.7 (5.8–9.9) uV, and 44.0 (42.0–47.0) m/s, respectively. Bilaterally absent responses were observed in 20.5% (n = 24) of subjects. Obese participants had a significantly higher number of absent saphenous responses (p = 0.033). Females had shorter peak-latency (p = 0.006) and higher conduction velocity (p = 0.012).ConclusionsSaphenous nerve responses can be used to assess unilateral femoral and saphenous nerve pathologies, provided they are recordable on the asymptomatic side for comparison. Absent bilateral saphenous nerve responses should be interpreted with caution given their prevalence in healthy individuals. Patient characteristics should be taken into consideration when interpreting recordable and nonrecordable saphenous nerve responses.

Source-sink mismatch and conduction block: simulation study

Abstract Background Source-sink mismatch is one of the key concepts in arrhythmia mechanism such as relationship between pulmonary veins and the left atrium in atrial fibrillation. We sought to find the condition for conduction block in various geometries. Methods To simulate cardiac atrial tissue, the finite element method was used to discretize the governing equation in a 2D mesh. We evaluated under the following conditions: 6 sizes of source width (0.1, 0.2, 0.3, 0.4, 0.5 and 0.6 mm), 64 types of angle (θ) at the junction (30-330 degrees), 3 conditions of conduction velocity (CV) (x0.5, x0.75, and x1 of normal CV of atrial myocardium). Results Conduction block was not observed with source width &amp;gt; 0.5 mm in any settings. In reduced CV condition, conduction block was not observed in θ &amp;lt; 300 degrees when source width &amp;gt; 0.3 mm. The higher CV, conduction block was observed in the narrower θ. In cases of CV of x1.0 and x0.75, conduction block was observed in θ &amp;lt; 180 degrees when source width &amp;lt; 0.3 mm. The smaller source width, conduction block was observed in the narrower θ. The wider θ, the easier conduction block occurred. Conclusion Conditions for conduction block due to source-sink mismatch are as follows: smaller source width, higher CV, and wider θ. Source with width &amp;gt; 0.5 mm may not be associated with source-sink mismatch in the atrial tissue. CV slowing by antiarrhythmic drugs can be effective in the aspect of source-sink mismatch.

Development of myelination and axon diameter for fast and precise action potential conductance.

Axons of globular bushy cells in the cochlear nucleus convey hyper-accurate signals to the superior olivary complex, the initial site of binaural processing via comparably thick axons and the calyx of the Held synapse. Bushy cell fibers involved in hyper-accurate binaural processing of low-frequency sounds are known to have an unusual internode length-to-axon caliber ratio (L/d) correlating with higher conduction velocity and superior temporal precision of action potentials. How the L/d-ratio develops and what determines this unusual myelination pattern is unclear. Here we describe a gradual developmental transition from very simple to complex, mature nodes of Ranvier on globular bushy cell axons during a 2-week period starting at postnatal day P6/7. The molecular composition of nodes matured successively along the axons from somata to synaptic terminals with morphologically and molecularly mature nodes appearing almost exclusively after hearing onset. Internodal distances are initially coherent with the canonical L/d-ratio of ~100. Several days after hearing onset, however, an over-proportional increase in axon caliber occurs in cells signaling low-frequency sounds which alters their L/d ratio to ~60. Hence, oligodendrocytes initially myelinating axons according to their transient axon caliber but a subsequent differential axon thickening after hearing onset results in the unusual myelination pattern.

Making an Effective Flipped Neuroscience Lab by Approaching Students from Their Emoticons.

During the pandemic, we filmed our neuroscience labs, and now the videos provide a great resource to flip the lab. Our lab, however, covers a wide range of complicated topics, ranging from gross anatomy, immunohistochemistry (IHC) staining, and fluorescence imaging to cockroach microscopic surgery and measuring nerve conduction velocity on worms and human subjects, and it is challenging to get students to finish watching these complicated experiments. The biggest challenge that students face while watching these experiment demonstrations is their own emotions. When we were editing the films of the labs, we did not reduce the complexity, but we explained concepts by using concepts and objects that students are already familiar with so we do not trigger anxiety. To reduce boredom, we employed three major methods: questioning, humor, and increasing the pace. To address potential anxiety or reluctance about the in-person part of the lab, we mention at the beginning of every lab session that making mistakes is completely acceptable and, as they make mistakes, we help them understand what went wrong and how to correct it. We also introduce additional activities in some lab sessions to pique their interest. For instance, we ask students to test the effects of Red Bull on crickets and investigate whether students who play more video games have higher conduction velocities in the median nerve. Thus far, our flipped lab has been quite successful in terms of maintaining video retention rates and in-person attendance rates. A notable example of the effectiveness of improved hands-on skills is the cockroach microscopic surgery. Before implementing the flipped lab, only 10% of students were able to successfully complete the surgery and acquire nerve activity recordings. With the flipped lab, 90% of students were able to obtain a recording independently.

Left atrium substrate and wave speed mapping using Omnipolar technology in patients undergoing paroxysmal atrial fibrillation catheter ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background The new Ensite X Cardiac Mapping (Abbott) system, with the introduction of Omnipolar technology (OT), provides three-dimensional information on voltage, direction of activation and conduction velocity of endocardial potentials, regardless of catheter orientation. OT thus enables the creation of more defined voltage maps and a wave speed map, a color map encoded by the numerical value of conduction velocity. Purpose We aimed to evaluate the feasibility and reliability of left atrium (LA) substrate and wave speed mapsperformed with OT in patients undergoing pulmonary vein isolation of paroxysmal atrial fibrillation (AF). Methods We included 39 patients undergoing catheter ablation for paroxysmal AF with the new Ensite X Cardiac Mapping System at five Italian Institution. In all patients the left atrium (LA) was mapped with the Advisor HD Grid catheter (Abbott). A sinus rhythm high-density voltage map and wave speed map were obtained and analyzed to compare low-voltage areas and to identify high conduction velocity areas. Results Thirty-nine pts were included in this analysis (61±10 years, 64% male, 68% with paroxysmal AF, CHA2DS2-VASc = 1.6±1.1, left atrial diameter = 46±9 mm, left ventricle ejection fraction 63±4%). The voltage maps were obtained by acquiring and, after point validation, analyzing significantly more points in the OT analysis than in the bipolar analysis (11455±8833 vs 8186±5826 and 2611±1728 vs 1753±1324, respectively; p &amp;lt; 0.001). Low-voltage area (&amp;lt; 0.05 mV) was significantly less extensive using OT (low-voltage OT area 8.9 cm2 [5.8; 24.2] vs low-voltage bipolar area 10.8 [6.4; 31.4]; p &amp;lt; 0.05), Fig 1. Considering wave speed maps, the pulmonary veins showed significantly higher values than the atrial values (LSPV: 2.89 ms/s ± 1.99; LIPV 2.86 ms/s ± 1.78; RSPV 3.31 ms/s ± 2.07; RIPV 2.86 ms/s ± 1.96; LA 1.67 ms/s ± 0.80; p&amp;lt; 0.001) while, in the atrium, the area of greatest speed was located on the roof (2.35 ms/s ± 1.53; p 0.02) almost drawing a bundle from the RSPV to the LA appendage that could coincide with the anatomical Bachmann’s bundle location, Fig 2. Conclusion OT makes it possible to obtain voltage maps by analyzing a larger number of points and providing a better substrate definition. Wave speed mapping is a promising new map type, allowing characterization and identification of high velocity areas. Further studies are needed to assess the impact of this new technology on procedural workflow and clinical outcome.

Different subtypes of motor cortex pyramidal tract neurons projects to red and pontine nuclei.

Pyramidal tract neurons (PTNs) are fundamental elements for motor control. However, it is largely unknown if PTNs are segregated into different subtypes with distinct characteristics. Using anatomical and electrophysiological tools, we analyzed in mice motor cortex PTNs projecting to red and pontine midbrain nuclei, which are important hubs connecting cerebral cortex and cerebellum playing a critical role in the regulation of movement. We reveal that the vast majority of M1 neurons projecting to the red and pontine nuclei constitutes different populations. Corticopontine neurons have higher conduction velocities and morphologically, a most homogeneous dendritic and spine distributions along cortical layers. The results indicate that cortical neurons projecting to the red and pontine nuclei constitute distinct anatomical and functional pathways which may contribute differently to sensorimotor integration.

Epicardial delivery of a conductive membrane synchronizes conduction to reduce atrial fibrillation.

Conductive polymers have been investigated as a medium for the transmission of electrical signals in biological tissues, but their capacity to rewire cardiac tissue has not been evaluated. Myocardial tissue is unique in being able to generate an electrical potential at a fixed rate; this potential spreads rapidly among cells to trigger muscle contractions. Tissue injuries result in myocardial fibrosis and subsequent non-uniform conductivity, leading to arrhythmia. Atrial fibrillation (AF) is the most common sustained arrhythmia, associated with disruption of atrial electrical signaling, which can potentially be restored by the epicardial delivery of conductive polymers. In this work, poly-3-amino-4-methoxybenzoic acid, conjugated to gelatin, is fabricated as a membrane (PAMB-G) to support conductive velocities that are close to that of the myocardium. A cross-linked gelatin membrane (Gelatin) is used as a control. The as-fabricated PAMB-G has similar tensile elasticities, determined using the Young's modulus, as contracting myocardium; it can also transmit electrical signals to initiate cardiac cell and tissue excitation. Delivering PAMB-G onto the atrium of a rat AF model shortens AF duration and improves post-AF recovery for the duration of a 28-day-long study. Atrial tissue in the PAMB-G-implanted group has lower impedance, higher conduction velocity, and higher field potential amplitude than that in the Gelatin-implanted group. Therefore, the as-proposed PAMB-G is a suitable medium for restoring proper cardiac electrical signaling in AF hearts.

Conduction velocity mapping in Bachmann Bundle using Omnipolar Technology

Abstract Funding Acknowledgements Type of funding sources: None. Background Bachmann’s bundle is emerging as a critical component of atrial fibrillation (AF) catheter ablation (CA). The introduction of Omnipolar Technology (OT) in the new Ensite X Cardiac Mapping system, provides three-dimensional information on conduction velocity, activation direction and voltage of endocardial potentials, independently of catheter orientation. OT can create a wave speed map: a color map type coded by numeric value of conduction velocity. Objective To assess the feasibility and reliability of left atrium wave speed maps in Bachmann’s bundle identification and conduction velocity characterization. Methods We included 10 patients, (60% male, 40% female, mean age 56±8.7 years) undergoing CA for paroxysmal AF at our institution with new Ensite X Cardiac Mapping System; the left atrium (LA) was mapped with the Advisor HD Grid catheter. A sinus rhythm voltage map and wave speed map were obtained and analyzed to identify high conduction velocity areas throughout the Bachmann’s bundle location (septum, roof and left atrium appendage (LAA)). Results Wave speed mapping allowed the identification, at the septum, roof and LAA, of a myocardial bundle with greater speed values (2.5±0.3 m/s) with respect to mean atrial value (1±0.1). Pulmonary vein antra conduction velocity mean value was 1.2±0.4 m/s. Standard voltage map (low-voltage areas defined as any LA region with voltage values &amp;lt; 0.5 mV) was compared with wave speed map. Standard voltage map (Figure 1) did not discriminate Bachmann’s bundle, while wave speed map did (Figure 2). Conclusion Wave speed mapping introduced by OT is a promising new map type, allowing characterization and identification of Bachmann’s bundle. Further studies are needed to assess the impact of this new technology on procedural workflow and clinical outcome.

BUNDLE BRANCH BLOCKS SIMULATIONS IN VENTRICULAR MODEL WITH REALISTIC GEOMETRY AND CONDUCTION SYSTEM

The goal of the study was to design a model of cardiac ventricles with realistic geometry that enables simulation of the ventricular activation with normal conduction system functions, as well as with bundle branch blocks. In ventricles, electrical activation propagates from the His bundle to the left and right bundle branches and continues to the fascicles and branching fibers of the Purkinje system. The role of these parts of the conduction system is to lead the activation rapidly and synchronously to the left and right ventricle. The velocity of propagation in the conduction system is several times higher than in the surrounding ventricular myocardium. If the conduction system works normally, QRS duration representing the total activation time of the ventricles lies in the physiological range of about 80 to 120 ms but it is more than 120 ms in the case of bundle branch blocks. In our study, the realistic geometry of the ventricles was constructed on the base of a patient CT scan, defining epicardial and endocardial surfaces. The first part of the conduction system (fast-conducting bundle branches, fascicles in the left ventricle and initial parts of the Purkinje fibers) was modeled as polyline pathways isolated from the surrounding ventricular tissue. The remaining part of the Purkinje system was modeled as an endocardial layer with higher conduction velocity. The propagation of the electrical activation in the ventricular model was modeled using reaction-diffusion (RD) equations, except for the first part of the conduction system, where the activation times were evaluated algebraically with respect to predefined velocity of propagation and estimated distance between the His bundle and particular entry point to the layer with higher conduction velocity. Propagation of activation in cardiac ventricles was numerically solved in Comsol Multiphysics environment. Several configurations of the first part of the conduction system with different number of polyline pathways and entry points were proposed and tested to achieve realistic activation propagation. For the model with 9 starting points, realistic total activation time (TAT) of the whole ventricles of about 108 ms was obtained for the model with normal conduction system, and realistic TAT of 126 ms and 149 ms were obtained for the right and left bundle branch block (RBBB, LBBB), respectively. Very similar TAT was found also for the model with 7 starting points, but unrealistically long TAT was obtained in LBBB simulation for the model with only 5 starting points.

B-PO04-195 IDENTIFICATION OF LOW-VOLTAGE AREAS: A UNIPOLAR, BIPOLAR AND OMNIPOLAR PERSPECTIVE

Low-voltage areas (LVA) are commonly considered a surrogate marker for arrhythmogenic tissue with slow conduction, thereby representing potential target sites for ablation therapy. As unipolar electrograms (EGM) comprise a larger region of myocardial electrical activity, bipolar EGM are mainly used to detect scar tissue. However, the efficacy of these strategies remains controversial due to mainly technical disadvantages. Therefore, a so-called omnipolar mapping technique has been recently developed which mathematically extracts maximal bipolar voltage from a collection of EGM. However, it remains unknown whether omnipolar voltages are complementary or contradictory to unipolar and bipolar voltages in classifying LVA. To examine similarities and dissimilarities in omnipolar, unipolar and bipolar voltage distribution and to explore the relation between various types of voltages and conduction velocity (CV). Intra-operative epicardial mapping (interelectrode distance 2mm) was performed during sinus rhythm in 21 patients (48±13 years, 9 male) with atrial volume overload. Cliques of 4 electrodes (2x2 mm) were used to define maximal omnipolar (Vomni,max), unipolar (Vuni,max) and bipolar (Vbi,max) voltages and mean CV. LVA were defined as Vbi,max or Vomni,max ≤0.5 mV. Vuni,max was larger than both Vbi,max and Vomni,max (7.08 [4.22-10.59] mV vs. 5.27 [2.39-9.56] mV and 5.77 [2.58-10.52] mV, P<0.001). The largest bipolar voltage was on average 1.66 (range: 1.0 - 59.0) times larger than the corresponding perpendicular bipolar voltages. LVA identified by a bipolar or omnipolar threshold were characterized by a large range of unipolar voltages and, even though CV was generally decreased, still high CVs and large unipolar voltages were found in these areas. In patients with congenital heart disease, considerable discrepancies regarding LVA were found, which are particularly important as LVA are considered a surrogate marker for arrhythmogenic tissue. Even using directional independent omnipolar voltage to identify LVA, high CVs and large unipolar voltages could still be found within these areas. Therefore, a combination of low unipolar and low omnipolar voltage may be more indicative of ‘true’ LVA.

Identification of Low-Voltage Areas: A Unipolar, Bipolar, and Omnipolar Perspective.

Background:Low-voltage areas (LVAs) are commonly considered surrogate markers for an arrhythmogenic substrate underlying tachyarrhythmias. It remains challenging to define a proper threshold to classify LVA, and it is unknown whether unipolar, bipolar, and the recently introduced omnipolar voltage mapping techniques are complementary or contradictory in classifying LVAs. Therefore, this study examined similarities and dissimilarities in unipolar, bipolar, and omnipolar voltage mapping and explored the relation between various types of voltages and conduction velocity (CV).Methods:Intraoperative epicardial mapping (interelectrode distance 2 mm, ±1900 sites) was performed during sinus rhythm in 21 patients (48±13 years, 9 male) with atrial volume overload. Cliques of 4 electrodes (2×2 mm) were used to calculate the maximal unipolar, bipolar, and omnipolar voltages and mean CV. Areas with maximal bipolar or omnipolar clique voltage ≤0.5 mV were defined as LVA.Results:The maximal unipolar clique voltage was not only larger than maximal bipolar clique voltage but also larger than maximal omnipolar clique voltage (7.08 [4.22–10.59] mV versus 5.27 [2.39–9.56] mV and 5.77 [2.58–10.52] mV, respectively, P<0.001). In addition, the largest bipolar clique voltage was on average 1.66 (range: 1.0–59.0) times larger to the corresponding perpendicular bipolar voltage pair. LVAs identified by a bipolar or omnipolar threshold corresponded to a broad spectrum of unipolar voltages and, although CV was generally decreased, still high CVs and large unipolar voltages were found in these LVAs.Conclusions:In patients with atrial volume overload, there were considerable discrepancies in the different types of LVAs. Additionally, the identification of LVAs was hampered by considerable directional differences in bipolar voltages. Even using directional independent omnipolar voltage to identify LVAs, high CVs and large unipolar voltages are present within these areas. Therefore, a combination of low unipolar and low omnipolar voltage may be more indicative of true LVAs.

Chronic fatigue syndrome: Abnormally fast muscle fiber conduction in the membranes of motor units at low static force load

ObjectiveChronic fatigue syndrome (CFS) and fibromyalgia (FM) are disorders of unknown etiology and unclear pathophysiology, with overlapping symptoms of – especially muscular –fatigue and pain. Studies have shown increased muscle fiber conduction velocity (CV) in the non-painful muscles of FM patients. We investigated whether CFS patients also show CV abnormalities. MethodsFemales with CFS (n = 25), with FM (n = 22), and healthy controls (n = 21) underwent surface electromyography of the biceps brachii, loaded up to 20% of maximum strength, during short static contractions. The mean CV and motor unit potential (MUP) velocities with their statistical distribution were measured. ResultsThe CV changes with force differed between CFS-group and both FM-group and controls (P = 0.01). The CV of the CFS-group increased excessively with force (P < 0.001), whereas that of the controls increased only slightly and non-significantly, and that of the FM-group did not increase at all. In the CFS-group, the number of MUPs conveying very high conduction velocities increased abundantly with force and the MUPs narrowed. ConclusionOur results suggest disturbed muscle membrane function in CFS patients, in their motor units involved in low force generation. Central neural deregulation may contribute to this disturbance. SignificanceThese findings help to detangle the underlying mechanisms of CFS.

On the nature of delays allowing anatomical re-entry involving the Purkinje network: a simulation study

Clinical observations suggest that the Purkinje network can be part of anatomical re-entry circuits in monomorphic or polymorphic ventricular arrhythmias. However, significant conduction delay is needed to support anatomical re-entry given the high conduction velocity within the Purkinje network. We investigated, in computer models, whether damage rendering the Purkinje network as either an active lesion with slow conduction or a passive lesion with no excitable ionic channel, could explain clinical observations. Active lesions had compromised sodium current and a severe reduction in gap junction coupling, while passive lesions remained coupled by gap junctions, but modelled the membrane as a fixed resistance. Both types of tissue could provide significant delays of over 100 ms. Electrograms consistent with those obtained clinically were reproduced. However, passive tissue could not support re-entry as electrotonic coupling across the delay effectively increased the proximal refractory period to an extremely long interval. Active tissue, conversely, could robustly maintain re-entry. Formation of anatomical re-entry using the Purkinje network is possible through highly reduced gap junctional coupling leading to slowed conduction.

Comparison of Muscle MEPs From Transcranial Magnetic and Electrical Stimulation and Appearance of Reflexes in Horses.

IntroductionTranscranial electrical (TES) and magnetic stimulation (TMS) are both used for assessment of the motor function of the spinal cord in horses. Muscular motor evoked potentials (mMEP) were compared intra-individually for both techniques in five healthy horses. mMEPs were measured twice at increasing stimulation intensity steps over the extensor carpi radialis (ECR), tibialis cranialis (TC), and caninus muscles. Significance was set at p < 0.05. To support the hypothesis that both techniques induce extracranially elicited mMEPs, literature was also reviewed.ResultsBoth techniques show the presence of late mMEPs below the transcranial threshold appearing as extracranially elicited startle responses. The occurrence of these late mMEPs is especially important for interpretation of TMS tracings when coil misalignment can have an additional influence. Mean transcranial motor latency times (MLT; synaptic delays included) and conduction velocities (CV) of the ECR and TC were significantly different between both techniques: respectively, 4.2 and 5.5 ms (MLTTMS–-MLTTES), and −7.7 and −9.9 m/s (CVTMS-CVTES). TMS and TES show intensity-dependent latency decreases of, respectively, −2.6 (ECR) and −2.7 ms (TC)/30% magnetic intensity and −2.6 (ECR) and −3.2 (TC) ms/30V. When compared to TMS, TES shows the lowest coefficients of variation and highest reproducibility and accuracy for MLTs. This is ascribed to the fact that TES activates a lower number of cascaded interneurons, allows for multipulse stimulation, has an absence of coil repositioning errors, and has less sensitivity for varying degrees of background muscle tonus. Real axonal conduction times and conduction velocities are most closely approximated by TES.ConclusionBoth intracranial and extracranial mMEPs inevitably carry characteristics of brainstem reflexes. To avoid false interpretations, transcranial mMEPs can be identified by a stepwise latency shortening of 15–20 ms when exceeding the transcranial motor threshold at increasing stimulation intensities. A ring block around the vertex is advised to reduce interference by extracranial mMEPs. mMEPs reflect the functional integrity of the route along the brainstem nuclei, extrapyramidal motor tracts, propriospinal neurons, and motoneurons. The corticospinal tract appears subordinate in horses. TMS and TES are interchangeable for assessing the functional integrity of motor functions of the spinal cord. However, TES reveals significantly shorter MLTs, higher conduction velocities, and better reproducibility.

Human Cardiac Progenitors Grown Under Microgravity Conditions Generate Myocytes With High Conduction Velocities

Clinical trials using human adipogenic mesenchymal stem cells (hAdMSC) for the treatment of cardiac diseases have shown improvement in cardiac function and were proven safe. However, hAdMSCs do not convert efficiently into cardiac myocytes or vasculature. Thus, reprogramming hADMSCs into mature myocytes may fare better in future investigations. To reprogram hAdMSCs into electrically conductive cardiac myocytes (CM), we pioneered a 3‐step reprogramming strategy that uses proven MESP1/ETS2 transcription factors, beta 2‐adrenergic receptor (b2AR) and micro‐gravity signaling induced in 3D cardio‐spheroids. In stage 1, ETS2 and MESP1 activated Nkx2.5, Tbx5, Mef2C, dHAND and GATA4 during the conversion of hAdMSCs into cardiac progenitor cells (CPCs). Next, in stage 2, b2AR activation repositioned CPCs into de novo myocytes, along with the appearance of RYR2, CAV2.1, CAV3.1, Nav1.5, SERCA2 and CX45 gene transcripts, myofibrils and action potentials. In stage 3, electrical conduction fostered by 3D cardio‐spheroids formed in a Synthecon®, Inc. rotating bioreactor that mimics micro‐gravity induced the appearance of hypoxic genes: HIF1a/b, PCG1a/b and NOS2 which coincided with the robust activation of adult contractile genes MYH6, MYH7 and TNNI3, ion channel genes and the appearance of hyperpolarization‐activated and cyclic nucleotide‐gated channels (HCN1‐4). Conduction velocities doubled to ~200mm/s after hypoxia, and doubled yet again after dissociation of the 3D cell clusters to ~400mm/s. By comparison, normal conduction velocities within working ventricular myocytes in the whole heart range from 0.5–1m/s. Epinephrine stimulation of stage‐3 myocytes in patches resulted in an increase in amplitude of the electrical wave, indicative of mature CMs. Our efficient protocol converted hAdMSC into highly conductive CM and demonstrated the potential utilization of stage‐3 cells for tissue engineering applications for cardiac repair.Support or Funding InformationSupported by a grant from the Center for Advanced Science in SpaceThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Verification of the effect of the axon fluid as a highly dielectric medium in the high-speed conduction of action potentials using a novel axon equivalent circuit.

Both sensory neurons and motor neurons transfer signals rapidly through long pathways. Such signals propagate as action potentials through neurons. In myelinated neurons, high conduction velocities of 120 m/s have been reported, even for axons of just 20 μm in diameter. Such a high conduction velocity is enabled by the characteristic morphology of a myelinated axon: repeated regions encased by long uniform myelin sheaths alternating with extremely short exposed regions of the axon called nodes of Ranvier, which generate extremely sharp action potentials. Although the need for the action potential to cross many nodes increases the relay time, it is still able to propagate rapidly. This phenomenon motivated us to derive a new mechanism of the action potential propagation. First, the dielectric effect of the axonal fluid was considered, and it was investigated whether the combination of the characteristic axonal morphology and the dielectric constant of the axonal fluid contributes significantly to the realization of high conduction velocities even with the inclusion of a large loss in the relay time. To this end, we propose a new axon equivalent circuit that incorporates the effect of the dielectric characteristics of the axonal fluid. It was confirmed that a realistically high conduction velocity could be calculated using the proposed circuit and that the dielectric constant calculated using the proposed circuit was in agreement with that of an ionic fluid similar to axonal fluid. Moreover, the contribution of the combination of the axonal morphology and axonal fluid to the conduction velocity was confirmed.

Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues

Despite increased use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for drug development and disease modeling studies, methods to generate large, functional heart tissues for human therapy are lacking. Here we present a “Cardiopatch” platform for 3D culture and maturation of hiPSC-CMs that after 5 weeks of differentiation show robust electromechanical coupling, consistent H-zones, I-bands, and evidence for T-tubules and M-bands. Cardiopatch maturation markers and functional output increase during culture, approaching values of adult myocardium. Cardiopatches can be scaled up to clinically relevant dimensions, while preserving spatially uniform properties with high conduction velocities and contractile stresses. Within window chambers in nude mice, cardiopatches undergo vascularization by host vessels and continue to fire Ca2+ transients. When implanted onto rat hearts, cardiopatches robustly engraft, maintain pre-implantation electrical function, and do not increase the incidence of arrhythmias. These studies provide enabling technology for future use of hiPSC-CM tissues in human heart repair.

Electrical Stimulation of Artificial Heart Muscle: A Look Into the Electrophysiologic and Genetic Implications.

Development of tissue-engineered hearts for treatment of myocardial infarction or biologic pacemakers has been hindered by the production of mostly arrhythmic or in-synergistic constructs. Electrical stimulation (ES) of these constructs has been shown to produce tissues with greater twitch force and better adrenergic response. To further our understanding of the mechanisms underlying the effect of ES, we fabricated a bioreactor capable of delivering continuous or intermittent waveforms of various types to multiple constructs simultaneously. In this study, we examined the effect of an intermittent biphasic square wave on our artificial heart muscle (AHM) composed of neonatal rat cardiac cells and fibrin gel. Twitch forces, spontaneous contraction rates, biopotentials, gene expression profiles, and histologic observations were examined for the ES protocol over a 12 day culture period. We demonstrate improved consistency between samples for twitch force and contraction rate, and higher normalized twitch force amplitudes for electrically stimulated AHMs. Improvements in electrophysiology within the AHM were noted by higher conduction velocities and lower latency in electrical response for electrically stimulated AHMs. Genes expressing key electrophysiologic and structural markers peaked at days 6 and 8 of culture, only a few days after the initiation of ES. These results may be used for optimization strategies to establish protocols for producing AHMs capable of replacing damaged heart tissue in either a contractile or electrophysiologic capacity. Optimized AHMs can lead to alternative treatments to heart failure and alleviate the limited donor supply crisis.

Decrease of muscle fiber conduction velocity correlates with strength loss after an endurance run

Monitoring surface electromyographic (EMG) signals can provide useful insights for characterizing muscle fatigue, which is defined as an exercise-induced strength loss. This experiment investigated the muscle fiber conduction velocity (CV) changes induced by an endurance run. The day before and immediately after a half-marathon run (21.097 km) 11 amateur runners performed maximum voluntary contractions (MVCs) of knee extensor muscles. During the MVC, multichannel EMG was recorded from the vastus lateralis and EMG amplitude and CV were calculated. After the run, knee extensors showed a decreased strength (−13 ± 9%, p = 0.001) together with a reduction in EMG amplitude (−13 ± 10%, p = 0.003) and in CV (−6 ± 8%, p = 0.032). Knee extensor strength loss positively correlated with vastus lateralis CV differences (r = 0.76, p = 0.006). Thus, the exercises-induced muscle fatigue was associated not only with a decrease in EMG amplitude, but also with a reduction in CV. This finding suggests that muscle fibers with higher CV (i.e. those with greater fiber size) were the most impaired during strength production after an endurance run.

Receptive field size, chemical and thermal responses, and fiber conduction velocity of rat chorda tympani geniculate ganglion neurons.

Afferent chorda tympani (CT) fibers innervating taste and somatosensory receptors in fungiform papillae have neuron cell bodies in the geniculate ganglion (GG). The GG/CT fibers branch in the tongue to innervate taste buds in several fungiform papillae. To investigate receptive field characteristics of GG/CT neurons, we recorded extracellular responses from GG cells to application of chemical and thermal stimuli. Receptive field size was mapped by electrical stimulation of individual fungiform papillae. Response latency to electrical stimulation was used to determine fiber conduction velocity. Responses of GG neurons to lingual application of stimuli representing four taste qualities, and water at 4°C, were used to classify neuron response properties. Neurons classified as SALT, responding only to NaCl and NH4Cl, had a mean receptive field size of six papillae. Neurons classified as OTHER responded to salts and other chemical stimuli and had smaller mean receptive fields of four papillae. Neurons that responded to salts and cold stimuli, classified as SALT/THERMAL, and neurons responding to salts, other chemical stimuli and cold, classified as OTHER/THERMAL, had mean receptive field sizes of six and five papillae, respectively. Neurons responding only to cold stimuli, categorized as THERMAL, had receptive fields of one to two papillae located at the tongue tip. Based on conduction velocity most of the neurons were classified as C fibers. Neurons with large receptive fields had higher conduction velocities than neurons with small receptive fields. These results demonstrate that GG neurons can be distinguished by receptive field size, response properties and afferent fiber conduction velocity derived from convergent input of multiple taste organs.