58 research outputs found
The electrophysiological effects of Endothelin-1 in human atrial myocytes
No full textIntroduction: Chronic heart failure (CHF) is associated with an increased incidence of atrial fibrillation (AF) and elevated levels of catecholamines and endothelin-1 (ET-1), each of which affects the atrial L-type calcium current (ICaL) and consequently action potentials.
Hypotheses: ET-1 modulates the effects of isoproterenol (ISO) on ICaL and action potentials in human atrial myocytes.
Methods: Atrial myocytes were isolated enzymatically from samples of right atrial appendage obtained from consenting patients in sinus rhythm undergoing cardiac surgery. The nystatin-perforated whole cell patch clamp technique was used at 37ºC to record ICaL and action potentials in voltage-clamp and current-clamp mode respectively.
Results: The current-voltage relationship of ICaL was bell-shaped, peaking at +10 mV with a current density of -4.8±0.4 pA/pF (mean± s.e.m., n=89 cells, 34 patients). ISO, 0.1 nM to 1 µM, increased peak ICaL in a concentration-dependent manner (n=4-46 cells) with a maximum response of 250± 53% above control and an approximate EC50 of 0.06 µM. Isoproterenol at 0.05 µM significantly increased peak ICaL from -4.7± 0.4 to -12.2± 0.9 pA/pF (P<0.05, Students t-test; n=64 cells). This adrenergic effect was reversed by ET-1 at all concentrations tested from 0.01 to 10 nM and was partially reversible upon ET-1 washout and in the presence of the specific ET-A receptor antagonist, FR139317 (n=5-12 cells). Neither ET-1 alone nor the ET-B receptor agonist Sarafotoxin S6c, at 10 nM, had an effect on ICaL.
Isoproterenol (0.05 µM) prolonged the action potential duration at 50% repolarisation (APD50) from 30± 7 to 46± 7 ms (P< 0.05, n=15 cells), but had no effect on APD90 nor the cellular ERP. These adrenergic effects on APD50 and SDs were also abolished by ET-1 at 10 nM (P< 0.05, n=15 cells). Superfusion with ET-1 (10 nM) alone had no significant effect on APD50, APD90, nor ERP (n=21 cells). There were no significant interactions between these electrophysiological effects and diseases states or chronic pre-operative drug therapy.
Spontaneous activity, defined as a depolarisation occurring during phase 3 of action potential repolarisation or a depolarisation of greater than 3 mV amplitude during phase 4, frequently interrupted action potential recordings during, but not prior to, superfusion with ISO. Using a repetitive stimulation protocol, ISO at 0.05 µM produced spontaneous depolarisations in 5 of 7 cells studied (P< 0.05, chi-2 test). Endothelin-1 at 10 nM abolished these depolarisations in all 5 cells (P< 0.05). Superfusion with ET-1 (10 nM) alone was associated with spontaneous depolarisations in significantly fewer cells (P< 0.05, n=2 of 13 cells).
In a retrospective univariate analysis, patient comorbidity and pre-operative drug therapy were not found to influence the electrophysiological effects observed.
Conclusions: ET-1 reversed adrenergically induced increases in peak ICaL, APD50 and SDs in human atrial myocytes. This anti-adrenergic effect may be expected to influence the occurrence of AF in patients irrespective of comorbidity or pre-operative drug therapy
Multiple sets of solutions for harmonic elimination PWM bipolar waveforms: Analysis and experimental verification
No full textMultiple sets of solutions for the selective harmonic elimination pulse-width modulation method for inverter control exist. These sets present an independent solution to the same problem but further investigation reveals that certain sets may offer an improved overall harmonic performance. In this paper, a minimization method is discussed as a way to obtain these multiple sets of switching angles. A simple distortion harmonic factor that takes into account the first two most significant harmonics present in the generated waveform is considered in order to evaluate the performance of each set. The bipolar waveform is thoroughly analyzed and two cases are considered; single-phase patterns which eliminate all odd harmonics and three-phase counterparts which eliminate only the nontriplen odd harmonics from the line-to-neutral pattern but such harmonics are naturally eliminated from the line-to-line waveform. Experimental results support the theoretical considerations reported in the paper
Public perceptions of the risks of deliberate contamination of the food supply in the United States
No full textThe threat of agricultural terrorism has increasing become the focal point of interest for government, industry, and the public. As such, interviews were conducted with 1,001 American adults to examine their knowledge, attitudes, and perceptions of the risks associated with contamination of the food supply and their likely responses to the threat of deliberate food contamination. Respondents were also randomly assigned to be interviewed about attitudes and behaviors related to one of four contaminants (anthrax, botulism, salmonella, and cyanide) that might be used in a deliberate contamination incident. The results suggest that Americans know little about the food supply chain or about likely points of vulnerability within the system. Yet, more than half say they have thought about terrorism and the food supply. The majority also say that future terrorist attacks on the food and water supply within the United States are likely, and are only somewhat confident in the ability of grocery stores and the federal government to ensure food safety. More than one-fifth believe that deliberate contamination already occurs at least ‘somewhat often’. While perceived risk varied based on the type of contaminant used in a deliberate attack on the food supply, there were no differences in respondents’ affective reactions. However, when asked to predict their behaviors in a deliberate food contamination event, there were differences reported in confidence in the food supply, the amount of food respondents would purchase, and in the length of time it would take for them to resume their pre-contamination buying behaviors.Poster presented December 5, 2005 at the 25th Annual Meeting of the Society for Risk Analysis, Orlando, Florida.Peer reviewe
Author Correction: Considerations in the search for epistasis
No full textBalvert M, Cooper-Knock J, Stamp J, et al. Author Correction: Considerations in the search for epistasis. Genome Biology . 2025;26(1): 12
The Short QT Syndrome Proposed Diagnostic Criteria
No full textObjectivesWe aimed to develop diagnostic criteria for the short QT syndrome (SQTS) to facilitate clinical evaluation of suspected cases.BackgroundThe SQTS is a cardiac channelopathy associated with atrial fibrillation and sudden cardiac death. Ten years after its original description, a consensus regarding an appropriate QT interval cutoff and specific diagnostic criteria have yet to be established.MethodsThe MEDLINE database was searched for all reported cases of SQTS in the English language, and all relevant data were extracted. The distribution of QT intervals and electrocardiographic (ECG) features in affected cases were analyzed and compared to data derived from ECG analysis from general population studies.ResultsA total of 61 reported cases of SQTS were identified. Index events, including sudden cardiac death, aborted cardiac arrest, syncope, and/or atrial fibrillation occurred in 35 of 61 (57.4%) cases. The cohort was predominantly male (75.4%) and had a mean QTc value of 306.7 ms with values ranging from 248 to 381 ms in symptomatic cases. In reference to the ECG characteristics of the general population, and in consideration of clinical presentation, family history, and genetic findings, a highly sensitive diagnostic scoring system was developed.ConclusionsBased on a comprehensive review of 61 reported cases of the SQTS, formal diagnostic criteria have been proposed that will facilitate diagnostic evaluation in suspected cases of SQTS. Diagnostic criteria may lead to a greater recognition of this condition and provoke screening of at-risk family members
Crossing the slow pathway bridge: A better method for decreasing long-term recurrences after cryoablation of atrioventricular nodal reentrant tachycardia?
No full textPost-operative atrial fibrillation is influenced by beta-blocker therapy but not by pre-operative atrial cellular electrophysiology
No full text<b>Introduction:</b> We investigated whether post-cardiac surgery (CS) new-onset atrial fibrillation (AF) is predicted by pre-CS atrial cellular electrophysiology, and whether the antiarrhythmic effect of beta-blocker therapy may involve pre-CS pharmacological remodeling.
<b>Methods and Results:</b> Atrial myocytes were obtained from consenting patients in sinus rhythm, just prior to CS. Action potentials and ion currents were recorded using whole-cell patch-clamp technique. Post-CS AF occurred in 53 of 212 patients (25%). Those with post-CS AF were older than those without (67 ± 2 vs 62 ± 1 years, P = 0.005). In cells from patients with post-CS AF, the action potential duration at 50% and 90% repolarization, maximum upstroke velocity, and effective refractory period (ERP) were 13 ± 4 ms, 217 ± 16 ms, 185 ± 10 V/s, and 216 ± 14 ms, respectively (n = 30 cells, 11 patients). Peak L-type Ca<sup>2+</sup> current, transient outward and inward rectifier K<sup>+</sup> currents, and the sustained outward current were −5.0 ± 0.5, 12.9 ± 2.4, −4.1 ± 0.4, and 9.7 ± 1.0 pA/pF, respectively (13-62 cells, 7-19 patients). None of these values were significantly different in cells from patients without post-CS AF (P > 0.05 for each, 60-279 cells, 29-86 patients), confirmed by multiple and logistic regression. In patients treated >7 days with a beta-blocker pre-CS, the incidence of post-CS AF was lower than in non-beta-blocked patients (13% vs 27%, P = 0.038). Pre-CS beta-blockade was associated with a prolonged pre-CS atrial cellular ERP (P = 0.001), by a similar degree (~20%) in those with and without post-CS AF.
<b>Conclusion:</b> Pre-CS human atrial cellular electrophysiology does not predict post-CS AF. Chronic beta-blocker therapy is associated with a reduced incidence of post-CS AF, unrelated to a pre-CS ERP-prolonging effect of this treatment
Nixon's “full-speech”: imaginary and symbolic registers of communication
No full textCommunicative interchanges play a foundational role in establishing the social. This being said, communicative behaviour can also lead to stalemates and conflict in which demands of recognition outweigh the prospect of hearing or saying anything beyond what is thought to be known. This paper foregrounds a dimension of communication often neglected by approaches prioritizing mass communications and new media technologies, namely the psychical and inter-subjective aspects of communicative exchange. More directly, this paper introduces and develops a Lacanian psychoanalytic theory of two interlinked registers of communicative behaviour. The first of these is the imaginary: the domain of one-to-one inter-subjectivity and behaviour that serves the ego and functions to consolidate the images subjects use to substantiate themselves. The second - far more disturbing and unpredictable - is the symbolic. It links the subject to a trans-subjective order of truth, it provides them with a set of socio-symbolic co-ordinates, and it ties them into a variety of roles and social contracts. In an elaboration of these two registers, illustrated by brief reference to Nixon’s admission of guilt in his interviews with David Frost, I pay particular attention to both the potentially transformative symbolic aspect of communicative behaviours and the ever-present prospect that such relations will ossify into imaginary impasses of mis-knowing (méconnaissance) and aggressive rivalry
The influence of cholinesterase inhibitor therapy for dementia on risk of cardiac pacemaker insertion: a retrospective, population-based, health administrative databases study in Ontario, Canada
No full textAbstract
Background
Cholinesterase inhibitors are used to treat the symptoms of dementia and can theoretically cause bradycardia. Previous studies suggest that patients taking these medications have an increased risk of undergoing pacemaker insertion. Since these drugs have a marginal impact on patient outcomes, it might be preferable to change drug treatment rather than implant a pacemaker. This population-based study determined the association of people with dementia exposed to cholinesterase inhibitor medication and pacemaker insertion.
Methods
We used data from the Ontario health administrative databases from January 1, 1993 to June 30, 2012. We included all community-dwelling seniors who had a code for dementia and were exposed to cholinesterase inhibitors (donezepil, galantamine, and rivastigmine) and/or drugs used to treat co-morbidities of hypertension, diabetes, depression and hypothyroidism. We controlled for exposure to anti-arrhythmic drugs. Observation started at first exposure to any medication and continued until the earliest of pacemaker insertion, death, or end of study.
Results
2,353,909 people were included with 96,000 (4.1%) undergoing pacemaker insertion during the observation period. Case–control analysis showed that pacemaker patients were less likely to be coded with dementia (unadjusted OR 0.42 [95%CI 0.41-0.42]) or exposed to cholinesterase inhibitors (unadjusted OR 0.39 [95%CI 0.37-0.41]). That Cohort analysis showed patients with dementia taking cholinesterase inhibitors had a decreased risk of pacemaker insertion (unadj-HR 0.58 [0.55-0.61]). Adjustment for patient age, sex, and other medications did not notably change results, as did restricting the analysis to incident users.
Conclusions
Patients taking cholinesterase inhibitors rarely undergo, and have a significantly reduced risk of, cardiac pacemaker insertion
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