Slow Conduction Research Articles

Pressurised water flow in fractured permafrost rocks revealed by borehole temperature, electrical resistivity tomography, and piezometric pressure

Abstract. Rock slope instabilities and failures from permafrost rocks are among the most significant alpine hazards in a changing climate and represent considerable threats to high-alpine infrastructure. While permafrost degradation is commonly attributed to rising air temperature and slow thermal heat propagation in rocks, the profound impact of water flow in bedrock permafrost on warming processes is increasingly recognised. However, quantifying the role of water flow remains challenging, primarily due to the complexities associated with direct observation and the transient nature of water dynamics in rock slope systems. To overcome the lack of a quantitative assessment, we combine datasets of rock temperature measured in two deep boreholes (2016–2023), with electrical resistivity tomography measurements repeated monthly in 2013 and 2023; the site-specific temperature–resistivity relation determined in the laboratory with samples from the study area; and borehole piezometer data. Field measurements were carried out at the permafrost-affected north flank of the Kitzsteinhorn (Hohe Tauern range, Austria), which is characterised by significant water outflow from open fractures during the melt season. Borehole temperature data demonstrate a seasonal maximum of the permafrost active layer of 4–5 m. They further show abrupt temperature changes (∼ 0.2–0.7 °C) at 2, 3, and 5 m depth during periods with enhanced water flow and temperature regime changes between 2016–2019 and 2020–2022 at 10 and 15 m depth, which cannot be explained solely by conductive heat transfer. Electrical resistivity measurements repeated monthly reveal a massive decrease in resistivity from June to July and the initiation of a low-resistivity (< 4 kΩ m) zone in the lower part of the rock slope in June, gradually expanding to higher rock slope sections until September. We hypothesise that the reduction in electrical resistivity of more than an order of magnitude, which coincides with abrupt changes in borehole temperature and periods of high water heads up to 11.8 m, provides certain evidence of snowmelt water infiltration into the rockwall becoming pressurised within a widespread fracture network during the thawing season. This study shows that, in addition to slow thermal heat conduction, permafrost rocks are subjected to sudden push-like warming events and long-lasting rock temperature regime changes, favouring accelerated bottom-up permafrost degradation and contributing to the build-up of hydrostatic pressure, potentially leading to slope instability.

Mechanistic Insights into Melatonin's Antiarrhythmic Effects in Acute Ischemia-Reperfusion-Injured Rabbit Hearts Undergoing Therapeutic Hypothermia.

The electrophysiological mechanisms underlying melatonin's actions and the electrophysiological consequences of superimposed therapeutic hypothermia (TH) in preventing cardiac ischemia-reperfusion (IR) injury-induced arrhythmias remain largely unknown. This study aimed to unveil these issues using acute IR-injured hearts. Rabbits were divided into heart failure (HF), HF+melatonin, control, and control+melatonin groups. HF was induced by rapid right ventricular pacing. Melatonin was administered orally (10 mg/kg/day) for four weeks, and IR was created by 60-min coronary artery ligation and 30-min reperfusion. The hearts were then excised and Langendorff-perfused for optical mapping studies at normothermia, followed by TH. Melatonin significantly reduced ventricular fibrillation (VF) maintenance. In failing hearts, melatonin reduced the spatially discordant alternans (SDA) inducibility mainly by modulating intracellular Ca2+ dynamics via upregulation of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) and calsequestrin 2 and attenuating the downregulation of phosphorylated phospholamban protein expression. In control hearts, melatonin improved conduction slowing and reduced dispersion of action potential duration (APDdispersion) by upregulating phosphorylated connexin 43, attenuating the downregulation of SERCA2a and phosphorylated phospholamban and attenuating the upregulation of phosphorylated Ca2+/calmodulin-dependent protein kinase II. TH significantly retarded intracellular Ca2+ decay slowed conduction, and increased APDdispersion, thereby facilitating SDA induction, which counteracted the beneficial effects of melatonin in reducing VF maintenance.

Predictors of the Short-Term Outcomes of Guillain-Barré Syndrome: Exploring Electrodiagnostic and Clinical Features.

Guillain-Barré syndrome (GBS), an acute inflammatory disorder of the peripheral nervous system, is characterized by muscle weakness and paralysis. Prompt identification of patients at a high risk of poor outcomes is crucial for timely intervention. In this study, we combined clinical data with nerve conduction study and electromyography data to identify the predictors of GBS outcomes. We retrospectively analyzed the data of patients with GBS who had received treatment at Chang Gung Memorial Hospital, Taiwan, between 1998 and 2022. Comprehensive clinical and electrophysiological data were collected. Statistical analyses were performed to identify the predictors of poor outcomes. The patients were stratified into two groups by their scores on the GBS Disability Scale: good (score ≤ 2) and poor (score > 2) outcome groups. The study finally included 24 GBS patients (mean age: 53.0 ± 20.9 years; female-to-male ratio: 2.3; good outcome group: 13; poor outcome group: 11). Compared with the good outcome group, the poor outcome group was old (43.0 ± 20.4vs. 64.0 ± 15.7, p = 0.011), had a short time-to-treatment period (12.9 ± 7.8vs. 6.5 ± 5.4 days, p = 0.033), exhibited more prevalent mechanical ventilation use (0vs. 36.4%, p = 0.017), and had a prolonged hospitalization duration (14.7 ± 10.2vs. 53.1 ± 20.0 days, p < 0.001). Poor outcomes were associated with low compound muscle action potential (CMAP), slow motor nerve conduction velocity (MNCV), abnormal F-wave latency, and more conduction block and temporal dispersion. In the subgroup of acute inflammatory demyelinating polyradiculoneuropathy (AIDP), there were 19 patients, out of which 10 had good outcomes, while nine had poor outcomes. The clinical features that differentiate between good and poor outcomes in the AIDP subgroup were similar to those observed in all GBS patients. Notably, the motor conduction features, including distal and proximal CMAP and MNCV of the median and tibial nerves (all p < 0.05), were particularly important electrodiagnostic features of outcome discrimination in the AIDP subgroup. Combining clinical data with nerve conduction study and electromyography data can assist in predicting outcomes of both GBS patients and the AIDP subgroup. Poor outcomes are associated with older age, a more abrupt onset pattern, low CMAP, and slow nerve conduction, and abnormal tibial F responses can predict poor outcomes. Early identification of high-risk patients facilitates tailored interventions. This highlights the importance of combining clinical and electrophysiological data in GBS management.

Termination Without Global Propagation in Re-Entrant Ventricular Tachycardia: Electrophysiologic Characteristics and 3D-Electroanatomical Mapping Analysis.

Termination of ventricular tachycardia (VT) by a pacing stimulus that does not generate a QRS complex (termination without global propagation [TWGP]) can be a marker for a critical re-entry circuit isthmus. However, the electrophysiologic and anatomic features of these sites and their relation to VT substrate defined by 3-dimensional electroanatomical maps (3D-EAM) remain unknown. This retrospective study aimed to characterize TWGP sites and their relation to VT substrate identified by 3D-EAM. A total of 632 consecutive cases of catheter ablation for scar-related VT at 2 University medical centers were reviewed to identify TWGP. TWGP was observed 12 times at 11 different sites in 10 patients (5 ischemic cardiomyopathy). The TWGP stimulus fell immediately before or synchronous with the QRS in all cases, and evidence of local capture despite absence of a QRS complex was observed 6 times. In 5 sites, pacing after VT termination produced a QRS different than the VT. Four sites were in dense scar areas (<0.1mV), and 6 in abnormal low voltage zone (0.1-1.5mV). Additional mapping or ablation that abolished VT were consistent with the TWGP site being in a VT isthmus. A substrate marker for VT of late potentials, evoked delayed potentials, or slow conduction was present at 6 of 11 TWGP sites. TWGP may be a marker for detecting a re-entry circuit isthmus that has escaped detection based on electrogram or pace mapping-based substrate mapping.

Unusual findings during transesophageal electrophysiology study

The article presents the results of a transesophageal electrophysiological study of a 39-year-old patient with a combination of an accessory pathway and dissociation of the atrioventricular node into fast and slow conduction zones. The criteria for identifying slow anterograde conduction along the accessory pathway and a rare mechanism for inducing paroxysmal reciprocal atrioventricular nodal tachycardia are discussed.

An observational study on efficacy of atrioventricular nodal slow pathway ablation in patients with atrioventricular nodal reentrant tachycardia and its influence on atrioventricular conduction function.

The study aimed to evaluate the effectiveness of atrioventricular nodal slow pathway ablation in patients with atrioventricular nodal reentrant tachycardia (AVNRT) and examine its impact on the atrioventricular conduction function. A retrospective analysis was performed on the clinical data of 90 AVNRT patients who underwent radiofrequency ablation at our institution between August 2018 and February 2021. Based on the presence or absence of slow pathway conduction during the procedure, patients were classified into the slow pathway elimination group (SPE group) and the slow pathway improvement group (SPI group). Procedure-related parameters, His bundle electrogram, atrioventricular nodal effective refractory period (AVN-ERP), Wenckebach point of anterograde atrioventricular nodal conduction (AVN-WKB), Wenckebach point of retrograde atrioventricular nodal conduction (VAV-WKB), myocardial function were compared between the 2 groups. Additionally, the recurrence rates 1 and 2 years post-ablation were noted. Both groups reported a 100% success rate for the procedure. Post-ablation, 42 patients exhibited persisting atrioventricular nodal slow pathway, whereas 48 showed its disappearance, signifying the absence of the jump phenomenon and atrial echo. Post-ablation, the SPI group showed an increase in slow pathway AVN-ERP compared to pre-ablation values (P < .05), with no significant change in the fast pathway AVN-ERP (P > .05). The SPE group showed a reduction in both slow pathway and fast pathway AVN-ERP post-ablation (P < .05). Post-ablation, both slow pathway and fast pathway AVN-ERP in the SPI group were higher than in the SPE group (P < .05). AVN-WKB and VAV-WKB values increased in both groups after ablation (P < .05). There were no recurrences 1 or 2 years after ablation in the SPE group and 1 case of recurrence 2 years after ablation in the SPI group (2.38%). Different ablation endpoints during radiofrequency ablation had no apparent impact on atrioventricular conduction time, recurrence rate, and myocardial function in patients with AVNRT, but they advanced AVN-WKB and VAV-WKB. Slow pathway improvement led to an elongation of slow pathway AVN-ERP, while slow pathway elimination resulted in a reduction of both slow pathway and fast pathway AVN-ERP.

Insulin mitigates acute ischemia-induced atrial fibrillation and sinoatrial node dysfunction ex vivo.

Acute atrial ischemia is a well-known cause of postoperative atrial fibrillation (POAF). However, mechanisms through which ischemia contributes to the development of POAF are not well understood. In this study, ex vivo Langendorff perfusion was used to induce acute ischemia/reperfusion in the heart to mimic POAF. Inducibility of atrial fibrillation (AF) was evaluated using programmed electrical stimulation and verified with open-atrium optical mapping. Compared with the control group without ischemia, 25 minutes of ischemia substantially increased the incidence of AF. The right atrium was more susceptible to AF than the left atrium. Administering insulin for 30 minutes before ischemia and during reperfusion with 25 minutes of ischemia greatly reduced the vulnerability to AF. However, insulin treatment during reperfusion only did not show substantial benefits against AF. Optical mapping studies showed that insulin mitigated ischemia-induced abnormal electrophysiology, including shortened action potential duration and effective refractory period, slowed conduction velocity, increased conduction heterogeneity, and altered calcium transients. In conclusion, insulin reduced the risk of acute ischemia/reperfusion-induced AF via improving the electrophysiology and calcium handling of atrial cardiomyocytes, which provides a potential therapy for POAF.

Shapes of direct cortical responses vs. short-range axono-cortical evoked potentials: The effects of direct electrical stimulation applied to the human brain

ObjectiveDirect cortical responses (DCR) and axono-cortical evoked potentials (ACEP) are generated by electrically stimulating the cortex either directly or indirectly through white matter pathways, potentially leading to different electrogenic processes. For ACEP, the slow conduction velocity of axons (median ≈ 4 m.s−1) is anticipated to induce a delay. For DCR, direct electrical stimulation (DES) of the cortex is expected to elicit additional cortical activity involving smaller and slower non-myelinated axons. We tried to validate these hypotheses. MethodsDES was administered either directly on the cortex or to white matter fascicles within the resection cavity, while recording DCR or ACEP at the cortical level in nine patients. ResultsShort but significant delays (≈ 2 ms) were measurable for ACEP immediately following the initial component (≈ 7 ms). Subsequent activities (≈ 40 ms) exhibited notable differences between DCR and ACEP, suggesting the presence of additional cortical activities for DCR. ConclusionDistinctions between ACEPs and DCRs can be made based on a delay at the onset of early components and the dissimilarity in the shape of the later components (>40 ms after the DES artifact). SignificanceThe comparison of different types of evoked potentials allows to better understand the effects of DES.

State of the Art: Mapping Strategies to Guide Ablation in Ischemic Heart Disease.

Catheter ablation to prevent ventricular tachycardia (VT) that emerges late after a myocardial infarction aims to interrupt the re-entry substrate. Interruption of potential channels and regions of slow conduction that can be identified during stable sinus or paced rhythm is often effective and a number of substrate markers for guiding this approach have been described. While there is substantial agreement with different markers in some patients, the different markers select different regions for ablation in others. Mapping during VT to identify critical re-entry circuit isthmuses is likely more specific, and most useful when VT is incessant or frequent during the procedure or when sinus rhythm substrate ablation fails. Both approaches are often combined. These methods for identifying and characterizing post-infarct-related arrhythmia substrate and the re-entry circuits are reviewed.

Cells of the adult mouse cardiac conduction system in wild type and Nkx2-5 heterozygous loss-of-function mutation

Abstract Background Specialised cardiomyocytes in the cardiac conduction system (CCS) generate and spread the electrical impulse that initiates synchronised heartbeats. Disrupted signal transduction in the atrioventricular (AV) node, a key electrical connection between atria and ventricles, causes AV block. AV block potentially leads to electromechanical uncoupling and sudden cardiac death. Nkx2-5 encodes a cardiac transcription factor that is critical for embryonic CCS formation. Heterozygous loss-of-function mutation of Nkx2-5 (Nkx2-5+/–) results in a hypoplastic CCS in humans and mice and progressive AV block. Purpose We aimed to create a cell atlas of the adult mouse CCS and define the consequences of Nkx2-5 haploinsufficiency on the structural organisation and transcript expression of CCS cells. Methods We performed single-nucleus RNA sequencing on the sinoatrial nodes, AV nodes, His bundles, right bundle branches (RBB) and moderator bands of 17 wild type and 14 Nkx2-5+/– mice (aged 13 to 35 weeks, 5159 CCS cells). Employing single-molecule fluorescent RNA in situ hybridisation (smFISH), we validated selected transcripts and examined the spatial organisation of identified cell populations. Results In the AV node, we identified two subpopulations of pacemaker cells that were spatially separated in the proximal and distal pacemaker region (Fig1). Within these subpopulations, expressed transcripts indicated an atrial-to-ventricular gradient of electrical activity, corresponding to their respective topography. We determined two subpopulations in the His bundle and RBB that were enriched for either slow or fast conduction markers. Spatially, the slow-conducting populations seemed to surround the fast-conducting ones and might act as electrical isolation (Fig1). In Nkx2-5+/- cells of the pacemaker AV node, His bundle, RBB and Purkinje fibres, genes involved in Slit-Robo signalling were dysregulated. Slit-Robo signalling was previously reported in neuronal differentiation and embryonic heart lumen formation. Slit ligand 3 was downregulated in Nkx2-5+/- pacemaker AV node cells (Slit3, log2FC = -2.22, p = 7.0e-42), as was the roundabout guidance receptor 1 (Robo1, log2FC = -0.96, p = 1.6e-4). By contrast, there was upregulation of neural EGF-like 1 (Nell1, log2FC = 3.18, p = 5.3e-6), an alternative ligand of roundabout guidance receptors. Altered Nell1 and Slit3 expressions were confirmed by smFISH (Fig2). Conclusions Our cell atlas defines new CCS cell populations with informative transcriptomic profiles and spatial organisation, providing insights into subpopulations in the AV junction where electrical signals switch from slow to fast conduction. We identified disrupted Slit-Robo signalling in Nkx2-5+/-, possibly impairing differentiation and maturation of the CCS and altering electrophysiologic functions. Our normative anatomical and transcription data on the CCS can inform future studies of cardiac electrophysiology and arrhythmias.Fig1 - Subpopulations in AV junctionFig2 - Nell1 smFISH in pacemaker AV node

Stochastic and alternating pacing paradigms to assess the stability of cardiac conduction

Reentry, the most common cause of severe arrhythmias, is initiated by slow conduction and conduction block. Hence, evaluating conduction velocity and conduction block is of primary importance. However, the assessment of cardiac conduction safety in experimental and clinical settings remains elusive. To identify markers of conduction instability that can be determined experimentally, we developed an approach based on new pacing paradigms. Conduction across a cardiac tissue expansion was assessed in computer simulations and in experiments using cultures of neonatal murine cardiomyocytes on microelectrode arrays. Simulated and in vitro tissues were paced at a progressively increasing rate, with stochastic or alternating variations of cycle length, until conduction block occurred. Increasing pacing rate led to conduction block near the expansion. When stochastic or alternating variations were introduced into the pacing protocol, the standard deviation and the amplitude of alternating variations of local conduction times emerged as markers of unstable conduction prone to block. In both simulations and experiments, conduction delays were prolonged at the expansion but increased only slightly during the pacing protocol. In contrast, these markers of instability increased several-fold, early before block occurrence. The first and second moments of these two metrics provided an estimation of the site of block and the accuracy of this estimation. Therefore, when beat-to-beat variations of pacing cycle length are introduced into a pacing protocol, the local variability of conduction permits to predict sites of block. Our pacing paradigms may have translational applications in clinical cardiac electrophysiology, particularly in identifying ablation targets during mapping procedures.

Protective effects of Boswellia and Curcuma extract on oxaliplatin-induced neuropathy via modulation of NF-κB signaling

Oxaliplatin is a third-generation anticancer agent with better efficacy, lower toxicity, and a broad spectrum of antineoplastic activity. Its use is frequently associated with chronic oxaliplatin-induced neuropathy (OIN), a cumulative phenomenon manifesting as loss of sensation, paresthesia, dysesthesia, and irresolvable fluctuations in proprioception that greatly affect the patients’ quality of life. The inevitable nature and high incidence of OIN, along with the absence of efficacious preventive agents, necessitate the development of effective and reliable protective options for limiting OIN while maintaining anticancer activity. The pathogenesis of chronic OIN involves neuroinflammation and oxidative stress. This study aimed to explore the neuroprotective effects of Boswellia serrata and Curcuma longa via modulation of nuclear factor-kappa B (NF-κB) signaling. Behavioral tests were conducted to assess cold allodynia, heat hyperalgesia, mechanical allodynia, mechanical hyperalgesia, and slowed nerve conduction velocity associated with chronic oxaliplatin administration. The modulation of NF-κB signaling and the subsequent activation of cytokines were evaluated through quantitative analysis of inflammatory cytokines in sciatic nerve homogenates. Additional assessments included oxidative stress parameters, serum neuronal biomarkers, and examination of sciatic nerve cross-sections. The findings indicate improvements in behavioral and biochemical parameters, as well as nerve histology, with the combined extract of Boswellia serrata and Curcuma longa at doses of 50 mg/kg and 75 mg/kg. Thus, this study presents evidence for the protective potential of the combined extract of Boswellia serrata and Curcuma longa in OIN through modulation of NF-κB signaling.

Examination of Proprioceptive Reliance During Backward Walking in Individuals With Multiple Sclerosis.

Slowed somatosensory conduction in multiple sclerosis (MS) increases postural instability and decreases proprioception. Despite these delays, individuals with MS rely more on proprioception for balance compared to controls. This heightened reliance, combined with slowed signal transduction, increases fall risk. Backward walking (BW) increases proprioceptive reliance by reducing visual cues. However, no study has conclusively linked proprioception to BW. This study aims to assess proprioception's role in BW compared to forward walking (FW) in MS and to compare differences in proprioception between MS fallers and non-fallers. Fifty participants (average age: 50.34±11.84, median Patient Determined Disease Steps [PDDS]: 2) completed the study. Participants completed BW and FW at comfortable and fast speeds. We have previously established vibration sensation as a proxy measure for proprioception. Vibration thresholds were quantified at the great toe bilaterally using a 2-alternative forced-choice procedure. Significant correlations were seen for vibration sensation and FW comfortable (ρ=0.35), FW fast (ρ=0.34), BW comfortable (ρ=0.46), and BW fast (ρ=0.46). After controlling for age, sex, and PDDS, vibration sensation significantly predicted performance during all walking tasks, with larger beta coefficients seen during BW (comfortable β=0.57; fast β=0.58) compared to FW (comfortable β=0.41; fast β=0.45). Fallers performed significantly worse than non-fallers for vibration sensation (P =0.04). Considering the notable decrease in proprioception in participants with MS and the clear distinction between fallers and non-fallers, it is crucial to conduct fall risk assessments and interventions focusing on proprioception. With its heightened reliance on proprioception, BW offers a promising method for assessing fall risk and could be an effective exercise intervention.

Dynamic Voltage Mapping of the Post-infarct Ventricular Tachycardia Substrate: A Practical Technique to Help Differentiate Scar from Borderzone Tissue.

During catheter ablation of post-infarct ventricular tachycardia (VT), substrate mapping is used when VT is non-inducible or poorly tolerated. Substrate mapping aims to identify regions of slowly conducting myocardium (borderzone) within and surrounding myocardial scar for ablation. Historically, these tissue types have been identified using bipolar voltage mapping, with areas of low bipolar voltage (<0.50 mV) defined as scar, and areas with voltages between 0.50 mV and 1.50 mV as borderzone. In the era of high-density mapping, studies have demonstrated slow conduction within areas of bipolar voltage <0.50 mV, suggesting that this historical cut-off is outdated. While electrophysiologists often adapt voltage cut-offs to account for this, the optimal scar-borderzone threshold is not known. In this review, we discuss dynamic voltage mapping, a novel substrate mapping technique we have developed, which superimposes data from both activation and voltage maps, to help delineate the post-infarct VT circuit through identification of the optimal scar-borderzone voltage threshold.

Sinoatrial node function and the role of sinoatrial conduction in the typical atrial flutter substrate

BackgroundSinoatrial node (SAN) activation and sinoatrial conduction pathways (SACPs) have been assessed in animals but not in humans. ObjectivesWe used ultrahigh-density mapping and simulated models to characterize the SAN and to investigate whether slowed SAN conduction may contribute to the atrial flutter (AFL) substrate. MethodsTwenty-seven patients undergoing electrophysiologic procedures had right atrial mapping. SAN activation patterns and conduction block were analyzed. The interaction between the SAN and the intercaval line of block (LOB) was analyzed, and right atrial simulations with different degrees of block were created to investigate arrhythmia mechanisms. ResultsFifteen AFL patients and 12 reference patients were enrolled. SACPs were identified in all patients with sinus rhythm maps. An SAN-adjacent LOB was observed in AFL patients. SAN conduction velocity was slower in AFL vs reference (0.60 m/s [0.56–0.78 m/s] vs 1.13 m/s [1.00–1.21 m/s]; P = .0021). Coronary sinus paced maps displayed an intercaval LOB in AFL patients but not in reference patients, which was completed superiorly by the SAN-adjacent LOB. Corrected sinus node recovery time was longer in AFL patients (552.3 ± 182.9 ms vs 325.4 ± 138.3 ms; P < .006) and correlated with degree of intercaval block (r = 0.7236; P = .0003). Computer modeling supported an important role of SAN-associated block in the flutter substrate. ConclusionUltrahigh-density mapping accurately identifies SAN activation and SACPs. The LOB important for typical AFL was longer in AFL patients, and when partial, it was always present inferiorly and completed superiorly because of slowed conduction across the SAN. Corrected sinus node recovery time correlated with intercaval block, suggesting a role for SAN disease in the genesis of the typical AFL substrate.

Novel ablation strategy to target slow conduction velocity areas in atrial fibrillation

Novel ablation strategy to target slow conduction velocity areas in atrial fibrillation

Firing properties of single axons with cardiac rhythmicity in the human cervical vagus nerve.

Microneurographic recordings of the human cervical vagus nerve have revealed the presence of multi-unit neural activity with measurable cardiac rhythmicity. This suggests that the physiology of vagal neurones with cardiovascular regulatory function can be studied using this method. Here, the activity of cardiac rhythmic single units was discriminated from human cervical vagus nerve recordings using template-based waveform matching. The activity of 44 cardiac rhythmic neurones (22 with myelinated axons and 22 with unmyelinated axons) was isolated. By consideration of each unit's firing pattern with respect to the cardiac and respiratory cycles, the functional identification of each unit was attempted. Of note is the observation of seven cardiac rhythmic neurones with myelinated axons whose activity was recruited or enhanced by slow, deep breathing, was maximal during the nadir of respiratory sinus arrhythmia, and showed an expiratory peak. This is characteristic of cardioinhibitory efferent neurones, which are responsible for respiratory sinus arrhythmia. The remaining 15 cardiac rhythmic neurones with myelinated axons were categorised as cardiopulmonary receptors or arterial baroreceptors based on the position of their peak in firing with respect to the R-wave of the cardiac cycle. This latter method is not viable for neurones with unmyelinated axons due to their slow and unknown conduction velocities. With the exception of three neurones whose expiratory modulation implicates them as cardiac-projecting efferent neurones, this population is likely dominated by arterial baroreceptors. In conclusion, the activity of single units with cardiovascular function has been discriminated within the human cervical vagus, enabling their systematic study. KEY POINTS: Recordings of the electrical activity of the vagus nerve have recently been made at the level of the neck in humans. Examination of the gross activity of this nerve reveals subpopulations of neurones whose activity fluctuates in time with the heart's beat, suggesting that the neurones that monitor or modify cardiac function can be studied using this method. Here, the activity of individual cardiac rhythmic neurones was isolated from human vagus nerve recordings using template-based spike sorting. The relationship between this activity and the cardiac and respiratory cycles was used as a means of classifying each neurone. Neuronal firing patterns that are consistent with that of neurones that modify cardiac function, including heart-slowing 'cardioinhibitory' neurones, as well as neurones that inform the brain of cardiovascular status were observed. This approach enables, for the first time, the systematic study of the function of these neurones in humans in both health and disease.

Estimating the Concentration of Heavy Metals in Oleander/Pink and white Oleander Plants

Oleander is a large ornamental evergreen shrub that may grow 20–25 ft in height. During the summer months’ large clusters of white, pink, red, or yellow (yellow oleander) flowers appear at the ends of the branches. All parts of the plant contain cardiac glycosides. Oleander is a common source of serious plant poisoning. In South Asia, particularly Sri Lanka, also present in Libya desert and some house gardens with white and pink types, oleander has become a notorious method of suicide. Toxicity is largely characterized by gastrointestinal symptoms and cardiac abnormalities. Tachy or bradydysthythmias may be present in addition to slowed conduction and heart block. Hyperkalemia is common and correlates with severity of poisoning. A specific antidote—digoxin-specific fragment antigen-binding region (Fab region)- is available. In Mediterranean climates oleanders can be expected to bloom from April through October, with the heaviest bloom usually occurring between May and June. Free-flowering varieties like 'Petite Salmon' or 'Mont Blanc' require no period of rest and can flower continuously throughout the year if the weather remains warm. The exact nature of plant poisoning varies from region to region, but certain plants are almost ubiquitous in distribution and among these, Oleander is a garden plant that features in many homes. Incidents of poisoning from these plants are therefore not uncommon and may be the result of accidental exposure or deliberate, suicidal ingestion of the toxic parts. An attempt has been made to review the management principles with regard to toxicity of these plants and survey the literature in order to highlight current concepts in the treatment of poisoning resulting from both plants. Ingestion of its seeds results in a clinical picture similar to digoxin toxicity. It contains cardiac glycosides that are toxic to cardiac myocytes and autonomic system. Cardiac glycosides of oleander cause poisoning by inhibiting plasmalemmal Na+/K+-ATPase. Results: The poisoning effects of plant or their active alkaloids induced infiltration of cells with hemorrhage and sever negative changes in the lung, induce lesions, and infiltration of inflammatory cells into the portal spaces with scattered necrosis of hepatocytes in the liver, cardiac toxicity of the plant in the heart were included, induced varying degrees of hemorrhage, myocardial degeneration, and necrosis. It also induced arrhythmia, sinus bradycardia, and prolonged P-R interval in electrocardiographic records. Conclusions: The toxic effects of N. oleander are mostly related to its inhibitory effects on the Naþ-Kþ ATPase pump in the cellular membrane. However, the exact molecular mechanism involved in the toxicity of N. oleander is not clear.

Slow left atrial conduction velocity in the anterior wall calculated by electroanatomic mapping predicts atrial fibrillation recurrence after catheter ablation-Systematic review and meta-analysis.

This study aimed to investigate and perform diagnostic test meta-analysis on whether slow left atrial conduction velocity (LACV) in the anterior wall calculated by electroanatomic mapping predicts atrial fibrillation (AF) recurrence after catheter ablation. Extensive literature search was performed on PubMed, SCOPUS, and EuropePMC up to June 5, 2024. The exposure group included AF patients with slow LACV in the anterior wall, while the control group included AF patients without slow LACV in the anterior wall. Slow LACV in the anterior wall was defined as LACV below study-specific cut-off points in m/s, measured by invasive electroanatomic mapping. The primary outcome of this study was AF recurrence, defined as AF/Atrial Flutter/Atrial Tachyarrhythmias lasting over 30 s at least 3 months after the blanking period postablation. This systematic review and meta-analysis included seven studies, involving a sample size of 1428 patients with mean follow-up duration were 13 months. Patients with AF recurrence has slower LACV in the anterior wall (mean difference - 0.16 m/s [-0.18, -0.15], p < .001). Slow LACV in the anterior wall defined as LACV below 0.70-0.88 m/s was associated with increased AF (adjusted OR 3.41 [1.55, 7.50], p = .002). Slow LACV in the anterior wall has an AUROC of 0.80 [0.76-0.83], sensitivity of 70% [52, 84], specificity of 76% [67, 83], positive likelihood ratio of 2.9 [2.3, 3.6], negative likelihood ratio of 0.39 [0.25, 0.63] for predicting AF recurrence postablation. Slow LACV in the anterior wall was associated with AF recurrence after catheter ablation.

Pacing cycle length–dependent electrophysiologic changes in left atrium: Poor validity of using low-voltage area and slow conduction area under specific pacing cycle length as absolute substrates of atrial fibrillation

BackgroundPacing cycle length (PCL)–dependent changes in left atrial (LA) electrophysiologic properties have not been fully elucidated. ObjectiveWe aimed to elucidate these changes using a high-resolution mapping system. MethodsForty-eight patients underwent atrial fibrillation ablation with RHYTHMIA HDx. Paired LA maps under a baseline PCL (600 ms) and rapid PCL (300 ms) were acquired after pulmonary vein isolation under right atrial appendage pacing. The PCL-dependent change in the low-voltage area (LVA; area with <0.5 mV bipolar voltage), LA activation time (interval from first LA activation to wavefront collision at lateral wall), regional mean voltage, regional mean wave propagation velocity, and slow conduction area (area with <0.3 m/s wave propagation velocity) were quantitatively analyzed. ResultsUnder the rapid PCL, the total LVA was significantly increased (7.6 ± 9.5 cm2 vs 6.7 ± 7.6 cm2; P = .031), especially in patients with a 10 cm2 LVA on the baseline PCL map (21.5 ± 9.1 cm2 vs 18.1 ± 6.5 cm2; P = .013). The LA activation time was also prolonged (87.9 ± 16.2 ms vs 84.0 ± 14.0 ms; P < .0001). Although the rapid PCL did not decrease the regional mean voltage, it significantly decreased the regional mean wave propagation velocity and increased the slow conduction area in all measured regions. ConclusionLVA and slow conduction area can be emphasized by rapid PCL LA mapping. There may be poor validity in using these areas as absolute atrial fibrillation substrates without considering the PCL-dependent changes.