Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study

Background Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood. Methods We simulated a 150 × 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution. Results Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms). Conclusion Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve

Ventricular Action Potential Adaptation to Regular Exercise: Role of β-adrenergic and K\u3csub\u3eATP\u3c/sub\u3e Channel Function

Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K+ (KATP) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6–8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca2+ transient durations reflected the changes in APD, while Ca2+ transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β1-AR blocker atenolol, but not the β2-AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β1-AR. At 10 Hz, the KATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β1-AR responsiveness and KATP channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca2+ influx; during exercise, an increase in KATP channel activity would shorten APD and, thus, protect the heart against Ca2+ overload or inadequate filling

A novel camera type for very high energy gamma-ray astronomy based on Geiger-mode avalanche photodiodes

Geiger-mode avalanche photodiodes (G-APD) are promising new sensors for light detection in atmospheric Cherenkov telescopes. In this paper, the design and commissioning of a 36-pixel G-APD prototype camera is presented. The data acquisition is based on the Domino Ring Sampling (DRS2) chip. A sub-nanosecond time resolution has been achieved. Cosmic-ray induced air showers have been recorded using an imaging mirror setup, in a self-triggered mode. This is the first time that such measurements have been carried out with a complete G-APD camera.Comment: 9 pages with 11 figure

On the limited amplitude resolution of multipixel Geiger-mode APDs

The limited number of active pixels in a Geiger-mode Avalanche Photodiode (G-APD) results not only in a non-linearity but also in an additional fluctuation of its response. Both these effects are taken into account to calculate the amplitude resolution of an ideal G-APD, which is shown to be finite. As one of the consequences, the energy resolution of a scintillation detector based on a G-APD is shown to be limited to some minimum value defined by the number of pixels in the G-APD.Comment: 5 pages, 3 figure

Rate-dependent propagation of cardiac action potentials in a one-dimensional fiber

Action potential duration (APD) restitution, which relates APD to the preceding diastolic interval (DI), is a useful tool for predicting the onset of abnormal cardiac rhythms. However, it is known that different pacing protocols lead to different APD restitution curves (RCs). This phenomenon, known as APD rate-dependence, is a consequence of memory in the tissue. In addition to APD restitution, conduction velocity restitution also plays an important role in the spatiotemporal dynamics of cardiac tissue. We present new results concerning rate-dependent restitution in the velocity of propagating action potentials in a one-dimensional fiber. Our numerical simulations show that, independent of the amount of memory in the tissue, waveback velocity exhibits pronounced rate-dependence and the wavefront velocity does not. Moreover, the discrepancy between waveback velocity RCs is most significant for small DI. We provide an analytical explanation of these results, using a system of coupled maps to relate the wavefront and waveback velocities. Our calculations show that waveback velocity rate-dependence is due to APD restitution, not memory.Comment: 17 pages, 7 figure

Police Alcohol-Related Services Study (PASS), Phase II: A Description of the Beliefs, Perceptions and Attitudes of Anchorage Police Department Employees

The principal aim of the Police Alcohol-related Services Study (PASS) was to expand knowledge about the fiscal, organizational, and cultural impact of citizen alcohol use on the Anchorage Police Department (APD). Phase II of the study employed a voluntary, self-administered questionnaire provided to all members of the APD regardless of rank, sworn status, or operational division. The questionnaire was designed to explore respondents' perceptions of their alcohol-related workload; perceptions of community problems; perceived links between alcohol use and selected social problems; attitudes, perceptions, and beliefs about the policing of alcohol-related incidents and the people involved with them; and personal and vicarious experience with alcohol-related incidents. The report describes survey response through comparison of APD employee responses across divisions within the department: operations vs. administration, patrol vs. non-patrol, and sworn vs. non-sworn.Part I. Project Overview & Summary of Findings / Part II. Alcohol-Related Workload: APD Employee Perspectives / Appendice

Ventricular Action Potential Adaptation to Regular Exercise: Role of β-adrenergic and K\u3csub\u3eATP\u3c/sub\u3e Channel Function

Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K+ (KATP) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6–8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca2+ transient durations reflected the changes in APD, while Ca2+ transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β1-AR blocker atenolol, but not the β2-AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β1-AR. At 10 Hz, the KATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β1-AR responsiveness and KATP channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca2+ influx; during exercise, an increase in KATP channel activity would shorten APD and, thus, protect the heart against Ca2+ overload or inadequate filling

Restricting excessive cardiac action potential and QT prolongation: a vital role for IKs in human ventricular muscle

Background - Although pharmacological block of the slow, delayed rectifier potassium current (I-Ks) by chromanol 293B, L-735,821, or HMR-1556 produces little effect on action potential duration (APD) in isolated rabbit and dog ventricular myocytes, the effect of IKs block on normal human ventricular muscle APD is not known. Therefore, studies were conducted to elucidate the role of IKs in normal human ventricular muscle and in preparations in which both repolarization reserve was attenuated and sympathetic activation was increased by exogenous dofetilide and adrenaline. Methods and Results - Preparations were obtained from undiseased organ donors. Action potentials were measured in ventricular trabeculae and papillary muscles using conventional microelectrode techniques; membrane currents were measured in ventricular myocytes using voltage-clamp techniques. Chromanol 293B (10 mu mol/L), L-735,821 (100 nmol/L), and HMR-1556 (100 nmol/L and 1 mu mol/L) produced a < 12-ms change in APD while pacing at cycle lengths ranging from 300 to 5000 ms, whereas the I-Kr blockers sotalol and E-4031 markedly lengthened APD. In voltage-clamp experiments, L- 735,821 and chromanol 293B each blocked IKs in the presence of E-4031 to block IKr. The E-4031-sensitive current (I-Kr) at the end of a 150-ms-long test pulse to 30 mV was 32.9 +/- 6.7 pA (n = 8); the L-735,821-sensitive current (I-Ks) magnitude was 17.8 +/- 2.94 pA (n = 10). During a longer 500-ms test pulse, IKr was not substantially changed (33.6 +/- 6.1 pA; n = 8), and I-Ks was significantly increased (49.6 +/- 7.24 pA; n = 10). On application of an "action potential-like" test pulse, I-Kr increased as voltage became more negative, whereas I-Ks remained small throughout all phases of the action potential - like test pulse. In experiments in which APD was first lengthened by 50 nmol/L dofetilide and sympathetic activation was increased by 1 mu mol/L adrenaline, 1 mu mol/L HMR-1556 significantly increased APD by 14.7 +/- 3.2% (P < 0.05; n = 3). Conclusions - Pharmacological IKs block in the absence of sympathetic stimulation plays little role in increasing normal human ventricular muscle APD. However, when human ventricular muscle repolarization reserve is attenuated, IKs plays an increasingly important role in limiting action potential prolongation

An impulsive noise analyser using amplitude probability distribution (APD) for broadband-wired communication

Electromagnetic interference or noise which is of impulsive nature is known to affect data communication performance. It is useful to correlate the characteristics of the noise with the bit error probability (BEP). The amplitude probability distribution (APD) has been proposed within CISPR for characterisation of the impulsive noise. However, there is no analyser available to perform direct measurement of the noise within the bandwidth of asymmetric digital subscriber line (ADSL2+) communication. This research presents a novel development of APD analyser for measurements of impulsive noise emission and its impact on ADSL2+ communication. A unique noise APD pattern is obtained from each measurement of noise emission from different electrical and electronic appliances. It is vital to have correct measurement set-up, signal power level, sampling rate, sample points and filter characterisation in order to acquire accurate data representation of the noise patterns. The APD graph is generated by the analyser using the APD algorithm method which employs the envelope sampling technique from actual probability. The noises are characterised using α-stable distribution which exhibits its own distinct APD parameters. The APD curve can be related with the single modulation scheme communication channel performance for estimation of bit error probability. The analyser has been developed successfully with dynamic range of 70 dB higher than the 60 dB CISPR 16 requirement, 0.02 dB amplitude resolution compared to 0.25 dB CISPR 16 requirement and 0.59 dB amplitude accuracy compared with the CISPR 16 standard of +/- 2.7 dB. In addition, the limits for noise in copper cable have been proposed for estimating the severity of the interference towards digital communication performance in ADSL2+ system. An advantage of the analyser is its ability to not only record the noise but the ability to regenerate back the noise which can be used for further analysis. In conclusion, the analyser can provide a comprehensive platform for impulsive noise interference verification towards ADSL2+ communication performance

A lens-coupled scintillation counter in cryogenic environment

In this work we present an elegant solution for a scintillation counter to be integrated into a cryogenic system. Its distinguishing feature is the absence of a continuous light guide coupling the scintillation and the photodetector parts, operating at cryogenic and room temperatures respectively. The prototype detector consists of a plastic scintillator with glued-in wavelength-shifting fiber located inside a cryostat, a Geiger-mode Avalanche Photodiode (G-APD) outside the cryostat, and a lens system guiding the scintillation light re-emitted by the fiber to the G-APD through optical windows in the cryostat shields. With a 0.8mm diameter multiclad fiber and a 1mm active area G-APD the coupling efficiency of the "lens light guide" is about 50%. A reliable performance of the detector down to 3K is demonstrated.Comment: 14 pages, 11 figure