Chronic beta-adrenoceptor blockade and human atrial cell electrophysiology: evidence of pharmacological remodelling

<b>Objective:</b> Chronic beta-adrenoceptor antagonist (β-blocker) treatment reduces the incidence of reversion to AF in patients, possibly via an adaptive myocardial response. However, the underlying electrophysiological mechanisms are presently unclear. We aimed to investigate electrophysiological changes in human atrial cells associated with chronic treatment with β-blockers and other cardiovascular-acting drugs. <b>Methods:</b> Myocytes were isolated enzymatically from the right atrial appendage of 40 consenting patients who were in sinus rhythm. The cellular action potential duration (APD), effective refractory period (ERP), L-type Ca<sup>2+</sup> current (<i>I</i><sub>CaL</sub>), transient (<i>I</i><sub>TO</sub>) and sustained (<i>I</i><sub>KSUS</sub>) outward K<sup>+</sup> currents, and input resistance (<i>R</i><sub>i</sub>) were recorded using the whole cell patch clamp. Drug treatments and clinical characteristics were compared with electrophysiological measurements using simple and multiple regression analyses. P<0.05 was taken as statistically significant. <b>Results:</b> In atrial cells from patients treated chronically with β-blockers, the APD<sub>90</sub> and ERP (75 beats/min stimulation) were significantly longer, at 213±11 and 233±11 ms, respectively (<i>n</i> = 15 patients), than in cells from non-β-blocked patients, at 176±12 and 184±12 ms (n = 11). These cells also displayed a significantly reduced action potential phase 1 velocity (22±3 vs. 34±3 V/s). Chronic β-blockade was also associated with a significant reduction in the heart rate (58±3 vs. 69±5 beats/min) and in the density of ITO (8.7±1.3 vs. 13.7±2.1 pA/pF), an increase in the Ri (214±24 vs. 132±14 MΩ), but no significant change in <i>I</i><sub>CaL</sub> or <i>I</i><sub>KSUS</sub>. The <i>I</i><sub>TO</sub> blocker 4-aminopyridine largely mimicked the changes in phase 1 and ERP associated with chronic β-blockade, in cells from non-β-blocked patients. Chronic treatment of patients with calcium channel blockers or angiotensin converting enzyme inhibitors (<i>n</i> = 11–13 patients) was not associated with any significant changes in atrial cell electrophysiology. <b>Conclusion:</b> The observed atrial cellular electrophysiological changes associated with chronic β-blockade are consistent with a long-term adaptive response, a type of ‘pharmacological remodelling’, and provide mechanistic evidence supportive of the anti-arrhythmic actions of β-blockade

Cortisol levels are positively associated with pup-feeding rates in male meerkats

In societies of cooperative vertebrates, individual differences in contributions to offspring care are commonly substantial. Recent attempts to explain the causes of this variation have focused on correlations between contributions to care and the protein hormone prolactin, or the steroid hormone testosterone. However, such studies have seldom considered the importance of other hormones or controlled for non-hormonal factors that are correlative with both individual hormone levels and contributions to care. Using multivariate statistics, we show that hormone levels explain significant variation in contributions to pup-feeding by male meerkats, even after controlling for non-hormonal effects. However, long-term contributions to pup provisioning were significantly and positively correlated with plasma levels of cortisol rather than prolactin, while plasma levels of testosterone were not related to individual patterns of pup-feeding. Furthermore, a playback experiment that used pup begging calls to increase the feeding rates of male helpers gave rise to parallel increases in plasma cortisol levels, whilst prolactin and testosterone levels remained unchanged. Our findings confirm that hormones can explain significant amounts of variation in contributions to offspring feeding, and that cortisol, not prolactin, is the hormone most strongly associated with pup-feeding in cooperative male meerkats

The Oxidation State of Iron in Silicate Minerals from the Matrices of CO Carbonaceous Chondrites

No abstract available

Atrial cellular electrophysiological changes in patients with ventricular dysfunction may predispose to AF

<b>Background:</b> Left ventricular systolic dysfunction (LVSD) is a risk factor for atrial fibrillation (AF), but the atrial cellular electrophysiological mechanisms in humans are unclear. Objective This study sought to investigate whether LVSD in patients who are in sinus rhythm (SR) is associated with atrial cellular electrophysiological changes that could predispose to AF. <b>Methods:</b> Right atrial myocytes were obtained from 214 consenting patients in SR who were undergoing cardiac surgery. Action potentials or ion currents were measured using the whole-cell-patch clamp technique. <b>Results:</b> The presence of moderate or severe LVSD was associated with a shortened atrial cellular effective refractory period (ERP) (209 ± 8 ms; 52 cells, 18 patients vs 233 ± 7 ms; 134 cells, 49 patients; P <0.05); confirmed by multiple linear regression analysis. The left ventricular ejection fraction (LVEF) was markedly lower in patients with moderate or severe LVSD (36% ± 4%, n = 15) than in those without LVSD (62% ± 2%, n = 31; P <0.05). In cells from patients with LVEF ≤ 45%, the ERP and action potential duration at 90% repolarization were shorter than in those from patients with LVEF > 45%, by 24% and 18%, respectively. The LVEF and ERP were positively correlated (r = 0.65, P <0.05). The L-type calcium ion current, inward rectifier potassium ion current, and sustained outward ion current were unaffected by LVSD. The transient outward potassium ion current was decreased by 34%, with a positive shift in its activation voltage, and no change in its decay kinetics. <b>Conclusion:</b> LVSD in patients in SR is independently associated with a shortening of the atrial cellular ERP, which may be expected to contribute to a predisposition to AF

Stratigraphic Architecture and Sediment Facies of the Western Oak Ridges Moraine, Humber River Watershed, Southern Ontario

The Oak Ridges Moraine in southern Ontario is a ca. 160 km long east-west trending ridge of sand and gravel situated north of Lake Ontario. Study of the Oak Ridges Moraine in the Humber River watershed was undertaken to assess its role in the groundwater system of the buried Laurentian Valley. The Oak Ridges Moraine is interpreted to have been deposited in three stages. Stage I records rapid deposition from hyperconcentrated flows where tunnel channels discharged into a subglacial lake in the Lake Ontario basin. Low-energy basin sedimentation of Stage II was in a subglacial and ice-contact setting of a highly crevassed ice sheet. Stage III sedimentation is characterized by rapid facies changes associated with esker, subaqueous fan, and basinal sedimentation. Detailed sediment analysis challenges the concept that the Oak Ridges Moraine was deposited principally from seasonal meltwater discharges, climatic modulated ice-marginal fluctuations, or in an interlobate position. Instead it is interpreted to have formed in response to late-glacial ice sheet events associated with subglacial meltwater ponding, episodic and catastrophic subglacial meltwater discharge, and subsequent seasonal meltwater discharge. The moraine probably formed as the glacial-hydraulic system re-equilibrated to the presence of a thinned, grounded ice shelf and a subglacial lake in the Lake Ontario basin.La moraine de Oak Ridges, sud de l’Ontario, est une crête de sable et de gravier orientée est-ouest d’une longueur de 160 km au nord du lac Ontario. L’étude de la moraine de Oak Ridges dans le bassin de la rivière Humber permet de comprendre son rôle dans le système de drainage de la vallée Laurentienne. La moraine de Oak Ridges a été édifiée en trois phases. La phase I consiste en une sédimentation rapide par hyperconcentration des écoulements, où les chenaux en tunnel se déversent dans un lac sous-glaciaire du lac Ontario. Le bassin de sédimentation de faible énergie de la phase II est sous-glaciaire et touche à un inlandsis ayant d’importantes crevasses. La phase III se caractérise par un changement de faciès très rapide, par la présence d’eskers, de cônes aquatiques et de bassins sédimentaires. Les analyses sédimentaires détaillées ébranlent l’hypothèse que la moraine de Oak Ridges ait été formée par la fonte des glaces saisonnière, les fluctuations climatiques près des marges glaciaires, ou dans une position interlobaire. Notre interprétation indique plutôt qu’elle a été mise en place en réponse à des événements de fonte sous-glaciaire de nature épisodique et catastrophique, et par des apports subséquents d’eau de fonte saisonnière. La moraine s’est probablement formée lors de la ré-équilibration du système glacio-hydraulique en présence d’un inlandsis mince, en contact avec le substrat et alimentant un lac sous-glaciaire dans le bassin du lac Ontario

ATCA radio detection of the new X-ray transient MAXI J1813-095 as a candidate radio-quiet black hole X-ray binary

We observed the new X-ray transient MAXI J1813-095 (ATels #11323, #11326, #11332) with the Australia Telescope Compact Array (ATCA) between 2018-02-22 20:52 UT and 2018-02-23 02:59 UT. Our observations were taken simultaneously at 5.5 and 9 GHz, with a bandwidth of 2 GHz at each frequency