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

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

Magnetic Resonance Force Microscopy Measurement of Entangled Spin States

We simulate magnetic resonance force microscopy measurements of an entangled spin state. One of the entangled spins drives the resonant cantilever vibrations, while the other remote spin does not interact directly with the quasiclassical cantilever. The Schr\"odinger cat state of the cantilever reveals two possible outcomes of the measurement for both entangled spins.Comment: 3 pages RevTe

Fast Quantum Search Algorithms in Protein Sequence Comparison - Quantum Biocomputing

Quantum search algorithms are considered in the context of protein sequence comparison in biocomputing. Given a sample protein sequence of length m (i.e m residues), the problem considered is to find an optimal match in a large database containing N residues. Initially, Grover's quantum search algorithm is applied to a simple illustrative case - namely where the database forms a complete set of states over the 2^m basis states of a m qubit register, and thus is known to contain the exact sequence of interest. This example demonstrates explicitly the typical O(sqrt{N}) speedup on the classical O(N) requirements. An algorithm is then presented for the (more realistic) case where the database may contain repeat sequences, and may not necessarily contain an exact match to the sample sequence. In terms of minimizing the Hamming distance between the sample sequence and the database subsequences the algorithm finds an optimal alignment, in O(sqrt{N}) steps, by employing an extension of Grover's algorithm, due to Boyer, Brassard, Hoyer and Tapp for the case when the number of matches is not a priori known.Comment: LaTeX, 5 page

Schemes for Parallel Quantum Computation Without Local Control of Qubits

Typical quantum computing schemes require transformations (gates) to be targeted at specific elements (qubits). In many physical systems, direct targeting is difficult to achieve; an alternative is to encode local gates into globally applied transformations. Here we demonstrate the minimum physical requirements for such an approach: a one-dimensional array composed of two alternating 'types' of two-state system. Each system need be sensitive only to the net state of its nearest neighbors, i.e. the number in state 1 minus the number in state 2. Additionally, we show that all such arrays can perform quite general parallel operations. A broad range of physical systems and interactions are suitable: we highlight two potential implementations.Comment: 12 pages + 3 figures. Several small corrections mad

Mechanically induced current and quantum evaporation from Luttinger liquids

We investigate transport through a tunnelling junction between an uncorrelated metallic lead and a Luttinger liquid when the latter is subjected to a time dependent perturbation. The tunnelling current as well as the electron energy distribution function are found to be strongly affected by the perturbation due to generation of harmonics in the density oscillations. Using a semiconducting lead instead of a metallic one results in electrons being injected into the lead even without applied voltage. Some applications to carbon nanotubes are discussed.Comment: 7 pages, 2 figures (eps files

An NMR-based nanostructure switch for quantum logic

We propose a nanostructure switch based on nuclear magnetic resonance (NMR) which offers reliable quantum gate operation, an essential ingredient for building a quantum computer. The nuclear resonance is controlled by the magic number transitions of a few-electron quantum dot in an external magnetic field.Comment: 4 pages, 2 separate PostScript figures. Minor changes included. One reference adde

Design and User Satisfaction of Interactive Maps for Visually Impaired People

Multimodal interactive maps are a solution for presenting spatial information to visually impaired people. In this paper, we present an interactive multimodal map prototype that is based on a tactile paper map, a multi-touch screen and audio output. We first describe the different steps for designing an interactive map: drawing and printing the tactile paper map, choice of multi-touch technology, interaction technologies and the software architecture. Then we describe the method used to assess user satisfaction. We provide data showing that an interactive map - although based on a unique, elementary, double tap interaction - has been met with a high level of user satisfaction. Interestingly, satisfaction is independent of a user's age, previous visual experience or Braille experience. This prototype will be used as a platform to design advanced interactions for spatial learning

Realistic simulations of single-spin nondemolition measurement by magnetic resonance force microscopy

A requirement for many quantum computation schemes is the ability to measure single spins. This paper examines one proposed scheme: magnetic resonance force microscopy, including the effects of thermal noise and back-action from monitoring. We derive a simplified equation using the adiabatic approximation, and produce a stochastic pure state unraveling which is useful for numerical simulations.Comment: 33 pages LaTeX, 9 figure files in EPS format. Submitted to Physical Review