Acidosis slows electrical conduction through the atrio-ventricular node

Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN). In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode's solution (20% CO2, pH 6.7) increased the time of earliest activation (Tact) from 100.5 ± 7.9 to 166.1 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode's solutions at pH 7.4 (control), 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH) interval, the AVN effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis

Detection of Highly Pathogenic Avian Influenza Virus H5N1 Clade 2.3.4.4b in Great Skuas:A Species of Conservation Concern in Great Britain

The UK and Europe have seen successive outbreaks of highly pathogenic avian influenza across the 2020/21 and 2021/22 autumn/winter seasons. Understanding both the epidemiology and transmission of these viruses in different species is critical to aid mitigating measures where outbreaks cause extensive mortalities in both land- and waterfowl. Infection of different species can result in mild or asymptomatic outcomes, or acute infections that result in high morbidity and mortality levels. Definition of disease outcome in different species is of great importance to understanding the role different species play in the maintenance and transmission of these pathogens. Further, the infection of species that have conservation value is also important to recognise and characterise to understand the impact on what might be limited wild populations. Highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b has been detected in great skuas (Stercorarius skua) across different colonies on islands off the shore of Scotland, Great Britain during summer 2021. A large number of great skuas were observed as developing severe clinical disease and dying during the epizootic and mortalities were estimated to be high where monitored. Of eight skuas submitted for post-mortem examination, seven were confirmed as being infected with this virus using a range of diagnostic assays. Here we overview the outbreak event that occurred in this species, listed as species of conservation concern in Great Britain and outline the importance of this finding with respect to virus transmission and maintenance

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The eternal divide?: history and international relations

On one level, history is used by all parts of the International Relations (IR) discipline. But lurking beneath the surface of IR’s approach to history lies a well-entrenched binary. Whereas mainstream positions use history as a means to fill in their theoretical frames (seeing history as a kind of ‘scripture’ of abstract lessons), many post-positivists reduce history to a pick-and-mix of contingent hiccups (a ‘butterfly’ of what-ifs and maybes). Interestingly enough, this binary is one reproduced throughout the social sciences. As such, there is a bigger story to the apparently ‘eternal divide’ between history and social science than first meets the eye. This article uses the various ways in which history is used — and abused — in IR to probe more deeply into the relationship between history and social science as a whole. This exploration reveals four frameworks, two drawn from history (context and narrative) and two drawn from social science (eventfulness and ideal-typification) which illustrate the necessary co-implication of the two enterprises. The article employs these tools as a means of re-imagining the relationship between history and social science (including IR), conceiving this as a single intellectual journey in which both are permanently in view

Atrial Tachycardia Arising From the Crista Terminalis, Detailed Electrophysiological Features and Long-Term Ablation Outcomes

Objectives: The goal of this study was to characterize, in detail, focal atrial tachycardia (AT) arising from the crista terminalis to investigate associations with other atrial arrhythmia and to define long-term ablation outcomes. Background: The crista terminalis is known to be the most common site of origin for focal AT, but it is not well characterized. Methods: This study retrospectively identified a total of 548 ablation procedures for AT performed at a single center over a 16-year period, of which 171 were arising from the crista terminalis. Results: Compared with patients with other AT sites of origin, crista terminalis AT patients were older (57.3 vs. 47.3 years), more commonly female (72.9% vs. 59.1%), were more commonly associated with coexistent atrioventricular nodal re-entry tachycardia (17.1% vs. 9.7%), and were more likely to be inducible with programmed stimulation (81.5% vs. 58.9%). There was preferential conduction in the superior-inferior axis along the crista terminalis. Acute ablation success rate was high (92.2%) and improved significantly when three-dimensional mapping was used (98.5%). Recurrence in the first 12 months after a successful ablation was 9.7%. Only 2 patients developed atrial fibrillation over the long-term follow-up of >7 years. Conclusions: This large series characterized the clinical and electrophysiological features and immediate and long-term ablation outcomes for AT originating from the crista terminalis. Features of the tachycardia suggest that age-related localized remodeling of the crista terminalis causes a superficial endocardial zone of conduction slowing leading to re-entry. Ablation outcomes were good, with long-term freedom from atrial arrhythmia

Isolation of the posterior left atrium for patients with persistent atrial fibrillation: routine adenosine challenge for dormant posterior left atrial conduction improves long-term outcome

Aims: Catheter ablation to achieve posterior left atrial wall (PW) isolation may be performed as an adjunct to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF). We aimed to determine whether routine adenosine challenge for dormant posterior wall conduction improved long-term outcome. Methods and results: A total of 161 patients with persistent AF (mean age 59 +/- 9 years, AF duration 6 +/- 5 years) underwent catheter ablation involving circumferential PVI followed by PW isolation. Posterior left atrial wall isolation was performed with a roof and inferior wall line with the endpoint of bidirectional block. In 54 patients, adenosine 15 mg was sequentially administered to assess reconnection of the pulmonary veins and PW. Sites of transient reconnection were ablated and adenosine was repeated until no further reconnection was present. Holter monitoring was performed at 6 and 12 months to assess for arrhythmia recurrence. Posterior left atrial wall isolation was successfully achieved in 91% of 161 patients (procedure duration 191 +/- 49 min, mean RF time 40 +/- 19 min). Adenosine-induced reconnection of the PW was demonstrated in 17%. The single procedure freedom from recurrent atrial arrhythmia was superior in the adenosine challenge group (65%) vs. no adenosine challenge (40%, P < 0.01) at a mean follow-up of 19 +/- 8 months. After multiple procedures, there was significantly improved freedom from AF between patients with vs. without adenosine PW challenge (85 vs. 65%, P = 0.01).Conclusion Posterior left atrial wall isolation in addition to PVI is a readily achievable ablation strategy in patients with persistent AF. Routine adenosine challenge for dormant posterior wall conduction was associated with an improvement in the success of catheter ablation for persistent AF

Progression of atrial remodeling in patients with high-burden atrial fibrillation:Implications for early ablative intervention

Abstract not availableTomos E.Walters, Ashley Nisbet, Gwilym M. Morris, Gabriel Tan, Megan Mearns, Eliza Teo, Nigel Lewis, AiVee Ng, Paul Gould, Geoffrey Lee, Stephen Joseph, Joseph B. Morton, Dominica Zentner, Prashanthan Sanders, Peter M. Kistler, Jonathan M. Kalma

Pulmonary vein isolation: the impact of pulmonary venous anatomy on long-term outcome of catheter ablation for paroxysmal atrial fibrillation

BACKGROUND Circumferential pulmonary vein (PV) isolation is the cornerstone of catheter ablation for atrial fibrillation (AF); however, PV reconnection remains problematic.OBJECTIVE To assess the impact of PV anatomy on outcome after AF ablation.METHODS One hundred two patients with paroxysmal AF underwent cardiac magnetic resonance (60%) or computed tomography (40%) before AF ablation. PV anatomy was classified according to the presence of common PVs, accessory PVs, PV branching pattern, and the dimensions of the PV ostia, intervenous ridges (IVRs), and the Left PV-left atrial appendage ridge.RESULTS Four discrete PVs were present in 48(47%) of the patients: a left common PV in 38(37%), a right common PV in 2 (2%), an accessory right PV in 20(20%), and left PV in 4(4%). At a mean follow-up of 12 +/- 4 months, 75 of 102 (74%) patients were free of recurrent AF. A LCPV was associated with an increase in freedom from AF (87% vs 66% for 4 PV anatomy; P = .03). Greater Left IVR length (16.9 +/- 3.5 mm vs 14.0 +/- 3.0 mm;