14 research outputs found
Impact of the intrinsic cardiac autonomic nervous system on ventricular arrhythmogenesis and inducibility of ventricular arrhythmia
No full textDas autonome Nervensystem beeinflusst alle Stellgrößen der kardialen Elektrophysiologie. Das neuronale Remodeling im Zuge akuter und vor allem chronischer Herzerkrankungen führt zu einer Dysbalance dieses Systems zugunsten eines gesteigerten Sympathikotonus. Der erhöhte adrenerge Tonus prädisponiert für die Genese maligner ventrikulärer Arrhythmien und ist damit Teil des Substrates des plötzlichen Herztodes.
Auf Organebene bilden autonome Nerven- und Ganglienplexus (GP) das intrinsische kardiale autonome Nervensystem (ICANS). Das ICANS wurde lange Zeit als reine parasympathische Relaisstation der vagalen Innervation verstanden. Mittlerweile ist bekannt, dass das ICANS der Integration zentraler Efferenzen sowie regionaler und peripherer Afferenzen in die regionale Regulation der Herzaktivität dient und ein wesentlicher Teil der autonomen Innervation darstellt. Ferner ist bekannt, dass die Neurone des ICANS auch nach zentraler Denervation ihre Aktivität nicht verlieren. Die funktionelle Bedeutung des ICANS für die ventrikuläre Elektrophysiologie, die Entstehung ventrikulärer Arrhythmien und den plötzlichen Herztod ist bisher nicht abschließend verstanden.
Ziel der vorliegenden Arbeit ist es, die Bedeutung des ICANS für die ventrikuläre Elektrophysiologie und die ventrikuläre Arrhythmogenese in der C57Bl/6-Wildtyp-Maus zu untersuchen. Hierzu wurde ein kombiniertes in-vivo und ex-vivo Modell zur elektrophysiologischen Untersuchung etabliert. Die im Rahmen dieser Arbeit durchgeführten Versuche erbrachten folgende Ergebnisse:
(1) Eine experimentelle Untersuchung des ICANS und dessen Bedeutung für die kardiale Elektrophysiologie im isolierten Organ ist möglich,
(2) das ICANS übt unabhängig von übergeordneten autonomen Zentren Einfluss auf die ventrikuläre Funktion aus und
(3) das ICANS beeinflusst die ventrikuläre Elektrophysiologie sowie die ventrikuläre Arrhythmogenese.
Somit konnte die Relevanz des ICANS für die ventrikuläre Elektrophysiologie und die Entstehung ventrikulärer Arrhythmien in der Maus dargestellt werden. Da die Architektur des ICANS des Menschen in Grundzügen mit der in kleineren Säugetieren zu vergleichen ist, könnte das ICANS in der Humanmedizin in der Therapie ventrikulärer Arrhythmien perspektivisch von Interesse sein.The autonomic nervous system modulates all variables of the cardiac electrophysiology. The neuronal remodeling due to acute and especially chronic heart diseases results in an impaired balance of this system for the benefit of an increased sympathetic tone. The elevated adrenergic tone predisposes towards ventricular arrhythmogenesis and therefore forms a substrate of sudden cardiac death.
On the level of the heart there is an extensive neural network consisting out of autonomic nerves and ganglionated plexi which form the intrinsic cardiac autonomic nervous system (ICANS). For a long period of time the ICANS was recognized as a simple parasympathetic relay station of the vagal innervation. Today it is known that the ICANS integrates central efferences on the one hand and sensory afferences on the other into regional cardiac regulation. Moreover, it is shown that the GPs do not lose neuronal activity after central denervation. Until now the functional meaning of the ICANS respecting the ventricular electrophysiological properties, ventricular arrhythmogenesis and sudden cardiac death stays unclear. The intention of this present work is to investigate the impact of the ICANS on the ventricular electrophysiology and the ventricular arrhythmogenesis in the C57Bl/6-wildtype-mouse. On that account a combined in-vivo and ex-vivo model was established. The findings of the experiments within the scope of this work demonstrated the following:
(1) The isolated heart is a suitable model to study the ICANS, its epicardial neurons and its impact on the ventricular electrophysiological properties,
(2) the ICANS impacts the ventricular function irrespective of central autonomic innervation and
(3) the ICANS affects the ventricular electrophysiological properties and the ventricular arrhythmogenesis.
In this work the relevance of the ICANS regarding the ventricular electrophysiological properties and the ventricular arrhythmogenesis is shown. Due to a similar neuronal architecture of the ICANS in man and smaller mammals the ICANS could be of interests to treat ventricular arrhythmias in human perspectively
Cardiac ischemia and reperfusion in mice: a comprehensive hemodynamic, electrocardiographic and electrophysiological characterization
No full textThe US4ABL Strategy: A Systematic Ultrasound-Guided Approach for Left Atrial and Ventricular Ablation Procedures
No full textBackground: The safety and efficacy of electrophysiological (EP) procedures using ultrasound (US) guidance are being increasingly studied. We investigated if a systematic workflow with ultrasound guidance (the US4ABL), comprising four steps (transesophageal echocardiography (TEE) for left atrial thrombus exclusion, US of the groin vessels to guide femoral access, TEE-aided transseptal puncture, and transthoracic echocardiography (TTE) for exclusion of pericardial tamponade after the procedure), reduces the number of complications and fluoroscopy duration and dose. Methods: A total of 212 consecutive patients underwent left-sided ablations using the US4ABL workflow and were compared to a group of 299 patients who underwent the same type of ablations using post-procedural TTE to exclude tamponade (standard group: venous and/or arterial access by palpation and fluoroscopy, and pressure guided transseptal puncture). Complications, procedural duration, fluoroscopy duration, and dose were compared. Results: The cohort included 511 patients (42% female); 43.8% of patients suffered from paroxysmal atrial fibrillation (AF), 35.4% presented with persistent AF, 10.7% underwent the procedure was for atrial tachycardia, and 10% of patients had premature ventricular contractions. The complication rate in the US4ABL group was lower compared to the standard group: 0 complications vs. 11 complications (3.7%, mainly vascular and pericardial), respectively (p = 0.005). The procedure times were lower in the US4ABL group (p < 0.01), whereas the fluoroscopy time and dose did not differ significantly. Conclusions: A fully ultrasound-guided (US4ABL) workflow for left atrial and ventricular electrophysiology procedures reduces the complication rate and the procedure time
Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias
No full textThe parasympathetic nervous system plays an important role in the pathophysiology of atrial fibrillation. Catheter ablation, a minimally invasive procedure deactivating abnormal firing cardiac tissue, is increasingly becoming the therapy of choice for atrial fibrillation. This is inevitably associated with the obliteration of cardiac cholinergic neurons. However, the impact on ventricular electrophysiology is unclear. Here we show that cardiac cholinergic neurons modulate ventricular electrophysiology. Mechanical disruption or pharmacological blockade of parasympathetic innervation shortens ventricular refractory periods, increases the incidence of ventricular arrhythmia and decreases ventricular cAMP levels in murine hearts. Immunohistochemistry confirmed ventricular cholinergic innervation, revealing parasympathetic fibres running from the atria to the ventricles parallel to sympathetic fibres. In humans, catheter ablation of atrial fibrillation, which is accompanied by accidental parasympathetic and concomitant sympathetic denervation, raises the burden of premature ventricular complexes. In summary, our results demonstrate an influence of cardiac cholinergic neurons on the regulation of ventricular function and arrhythmogenesi
A modified approach for programmed electrical stimulation in mice: Inducibility of ventricular arrhythmias
No full textBackgroundElectrophysiological studies in mice, the prevailing model organism in the field of basic cardiovascular research, are impeded by the low yield of programmed electrical stimulation (PES).ObjectiveTo investigate a modified approach for ventricular arrhythmia (VA) induction and a novel scoring system in mice.MethodA systematic review of literature on current methods for PES in mice searching the PubMed database revealed that VA inducibility was low and ranged widely (4.6 ± 10.7%). Based on this literature review, a modified PES protocol with 3 to 10 extrastimuli was developed and tested in comparison to the conventional PES protocol using up to 3 extrastimuli in anesthetized wildtype mice (C57BL/6J, n = 12). Induced VA, classified according to the Lambeth Convention, were assessed by established arrhythmia scores as well as a novel arrhythmia score based on VA duration.ResultsPES with the modified approach raised both the occurrence and the duration of VA compared to conventional PES (0% vs 50%; novel VA score p = 0.0002). Particularly, coupling of >6 extrastimuli raised the induction of VA. Predominantly, premature ventricular complexes (n = 6) and ventricular tachycardia ConclusionOur findings suggest that the presented approach of modified PES enables effective induction and quantification of VA in wildtype mice and may well be suited to document and evaluate detailed VA characteristics in mice.</div
Exercise‐induced dynamic mitral regurgitation is associated with outcomes in patients with ischaemic cardiomyopathy
No full textAbstract Aims Ischaemic mitral regurgitation (MR) is a dynamic condition influenced by global and regional left ventricular remodelling as well as mitral valvular deformation. Exercise testing plays a substantial role in assessing the haemodynamic relevance of MR and is recommended by current guidelines. We aimed to assess the prevalence, haemodynamic consequences, and prognostic impact of dynamic MR using isometric handgrip exercise. Methods and results Heart failure patients with ischaemic cardiomyopathy and at least mild MR who underwent handgrip echocardiography at the University Hospital Duesseldorf between January 2018 and September 2021 were enrolled. Patients were followed‐up for 1 year to assess a combined endpoint including all‐cause mortality, heart failure hospitalization, mitral valve surgery/interventions, ventricular assist device implantation and heart transplantation. One hundred thirty‐three patients with ischaemic cardiomyopathy were included (age 75 ± 10 years; 21% female; LVEF 35 ± 9%). At rest, 70 patients (53%) presented with mild MR, 54 patients had moderate MR (41%), and 9 patients (7%) showed severe MR. Twenty‐five patients (20%) with non‐severe MR at rest, developed severe MR during handgrip exercise. Patients with dynamic MR had larger left atrial dimensions, increased wall motion score index and larger tenting area at rest. Multivariate analysis identified MR severity during exercise [HR 1.998 (1.367–2.938)] and exercise TAPSE [HR 0.913 (0.853–0.973)] as predictors of the combined endpoint. Conclusions The haemodynamic changes provoked by isometric exercise unmasked dynamic severe MR in a significant number of patients with non‐severe MR at rest. These data may have implications for therapeutic decision‐making in symptomatic patients with non‐severe MR at rest
Systematic classification of ventricular arrhythmias based on the Lambeth criteria.
No full textFour types of ventricular arrhythmias are defined by international guidelines (11). A single premature ventricular complex (A), a ventricular couplet (B), triplet (C) and a ventricular tachycardia (D). Vertical arrow heads assign each premature ventricular complex. The horizontal square brackets depict programmed electrical stimulation. Surface electrocardiogram Einthoven lead I, intracardiac bipolar electrogram from mid RV and stimulus output are displayed.</p
Ventricular arrhythmia induction with the miniburst protocol.
No full textModified PES (MB) yielded VA in up to 50% of tested animals (n = 12). Inducibility increased when coupling of >6 extrastimuli (S4-S6 vs S7-S11 p = 0.011) (A). Predominantly, PVCs or VT of a duration less than 1 sec. were seen. PVC vs VT>1s p = 0.031, VT1s p = 0.030, Couplet vs VT>1s p = 0.096. Data plot as box and whiskers (B). Qualitative display of the number of extrastimuli in correlation with arrhythmia type. Quantity and duration of VA increased when coupling 7, 8 and 10 extrastimuli by means of ventricular events (MB S8 vs PES S2S3/S2S3S4 p = 0.011, MB S9 vs PES S2S3/S2S3S4 p = 0.025, MB S10 vs PES S2S3/S2S3S4 p = 0.312, MBS11 vs PES S2S3/S2S3S4 p = 0.0002). Stars represent animals affected (C).</p
Results of systematic literature research concerning in vivo programmed ventricular stimulation in mice.
No full textResults of systematic literature research concerning in vivo programmed ventricular stimulation in mice.</p
Scoring systems of ventricular arrhythmias.
No full textScoring systems of ventricular arrhythmias.</p
