Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes

Reperfusion-induced ventricular fibrillation (VF) severely threatens the lives of post-myocardial infarction patients. Carbon monoxide (CO) - produced by haem oxygenase in cardiomyocytes - has been reported to prevent VF through an unknown mechanism of action. Here, we report that CO prolongs action potential duration (APD) by inhibiting a subset of inward-rectifying potassium (Kir) channels. We show that CO blocks Kir2.2 and Kir2.3 but not Kir2.1 channels in both cardiomyocytes and HEK-293 cells transfected with Kir. CO directly inhibits Kir2.3 by interfering with its interaction with the second messenger phosphatidylinositol (4,5)-bisphosphate (PIP 2). As the inhibition of Kir2.2 and Kir2.3 by CO prolongs APD in myocytes, cardiac Kir2.2 and Kir2.3 are promising targets for the prevention of reperfusion-induced VF. © 2014 Macmillan Publishers Limited. All rights reserved.

Analysis and improvement of performance in LCL filter-based PWM rectifier/inverter application using hybrid damping approach

A hybrid passive-active damping solution with improved system stability margin and enhanced dynamic performance is proposed for high power grid interactive converters. In grid connected active rectifier/inverter application, line side LCL filter improves the high frequency attenuation and makes the converter compatible with the stringent grid power quality regulations. Passive damping though offers a simple and reliable solution but it reduces overall converter efficiency. Active damping solutions do not increase the system losses but can guarantee the stable operation up to a certain speed of dynamic response which is limited by the maximum bandwidth of the current controller. This paper examines this limit and introduces a concept of hybrid passive-active damping solution with improved stability margin and high dynamic performance for line side LCL filter based active rectifier/inverter applications. A detailed design, analysis of the hybrid approach and trade-off between system losses and dynamic performance in grid connected applications are reported. Simulation and experimental results from a 10 kVA prototype demonstrate the effectiveness of the proposed solution. An analytical study on system stability and dynamic response with the variations of various controller and passive filter parameters is presented.

Molecular basis of native inward rectifier currents : role of Kir2 subunits

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Molecular basis of native inward rectifier currents : role of Kir2 subunits

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

A Family of Autoconnected Transformers for 12-and 18-Pulse Converters-Generalization for Delta and Wye Topologies

Multipulse rectifier topologies based on autoconnections are increasingly applied as interface stages between mains and power electronics converters. These topologies are attractive and cost-effective solutions for meeting the requirements of low total harmonic distortion of line current and high power factor. Furthermore, as only a small fraction of the total power required by the load is processed in the magnetic core, the overall resulting volume and weight are reduced. This paper proposes a mathematical analysis based on phasor diagrams that results in a single and general expression capable of unifying all delta and wye step-up or step-down autotransformer connections for 12-and 18-pulse ac-dc converters. The expression obtained allows the choice of a wide range of input/output voltage ratio for step-up or step-down autotransformer, and this general expression is also presented in a graphical form for each converter. Moreover, it simplifies the procedure for determining turn ratios and polarities for all windings of the autotransformer. A routine for easy and fast calculations is developed and validated by a design example. Finally, experimental results are presented along with comments on a 6-kW 220-V line voltage, 400-V rectified voltage, and 18-pulse delta-autoconnected prototype.

Comparison Between Voltage Control Structures of Synchronous Machines

This paper compares the behaviour of two different control structures of automatic voltage regulators of synchronous machines equipped with static excitation systems. These systems have a fully controlled thyristor bridge that supplies DC current to the rotor winding. The rectifier bridge is fed by the stator terminals through a step-down transformer. The first control structure, named ""Direct Control"", has a single proportional-integral (PI) regulator that compares stator voltage setpoint with measured voltage and acts directly on the thyristor bridge`s firing angle. This control structure is usually employed in commercial excitation systems for hydrogenerators. The second structure, named ""Cascade Control"", was inspired on control loops of commercial DC motor drives. Such drives employ two PIs in a cascade arrangement, the external PI deals with the motor speed while the internal one regulates the armature current. In the adaptation proposed, the external PI compares setpoint with the actual stator voltage and produces the setpoint to the internal PI-loop which controls the field current.

Rectification of the olfactory cyclic nucleotide-gated channel by intracellular polyamines

Polyamine-induced inward rectification of cyclic nucleotide-gated channels was studied in inside-out patches from rat olfactory neurons. The polyamines, spermine, spermidine and putrescine, induced an 'instantaneous' voltage-dependent inhibition with K-d values at 0 mV of 39, 121 mu M and 2.7 mM, respectively. Hill coefficients for inhibition were significantly < 1, suggesting an allosteric inhibitory mechanism. The Woodhull model for voltage-dependent block predicted that all 3 polyamines bound to a site 1/3 of the electrical distance through the membrane from the internal side. Instantaneous inhibition was relieved at positive potentials, implying significant polyamine permeation. Spermine also induced exponential current relaxations to a 'steady-state' impermeant level. This inhibition was also mediated by a binding site 1/3 of the electrical distance through the pore, but with a K-d of 2.6 mM. Spermine inhibition was explained by postulating two spermine binding sites at a similar depth. Occupation of the first site occurs rapidly and with high affinity, but once a spermine molecule has bound, it inhibits spermine occupation of the second binding site via electrostatic repulsion. This repulsion is overcome at higher membrane potentials, but results in a lower apparent binding affinity for the second spermine molecule. The on-rate constant for the second spermine binding saturated at a low rate (similar to 200 sec(-1) at +120 mV), providing further evidence for an allosteric mechanism. Polyamine-induced inward rectification was significant at physiological concentrations.

Developmental changes in hyperpolarization-activated currents I-h and I-K(IR) in isolated rat intracardiac neurons

The hyperpolarization-activated nonselective cation current, I-h, was investigated in neonatal and adult rat intracardiac neurons. I-h was observed in all neurons studied and displayed slow time-dependent rectification. I-h was isolated by blockade with external Cs+ (2 mM) and was inhibited irreversibly by the bradycardic agent, ZD 7288. Current density of I-h was approximately twofold greater in neurons from neonatal (-4.1 pA/pF at -130 mV) as compared with adult (-2.3 pA/pF) rats; however, the reversal potential and activation parameters were unchanged. The reversal potential and amplitude of I-h was sensitive to changes in external Na+ and K+ concentrations. An inwardly rectifying K+ current, I-K(IR), was also present in intracardiac neurons from adult but not neonatal rats and was blocked by extracellular Ba2+. I-K(IR) was present in approximately one-third of the adult intracardiac neurons studied, with a current density of -0.6 pA/pF at -130 mV. I-K(IR) displayed rapid activation kinetics and no time-dependent rectification consistent with the rapidly activating, inward K+ rectifier described in other mammalian autonomic neurons. I-K(IR) was sensitive to changes in external K+, whereby raising the external K+ concentration from 3 to 15 mM shifted the reversal potential by approximately +36 mV. Substitution of external Na+ had no effect on the reversal potential or amplitude of I-K(IR). I-K(IR) density increases as a function of postnatal development in a population of rat intracardiac neurons, which together with a concomitant decrease in I-h may contribute to changes in the modulation of neuronal excitability in adult versus neonatal rat intracardiac ganglia.

Effects of dofetilide on cardiovascular tissues from normo- and hypertensive rats

The aim was to test whether dofetilide has some potential for use in the treatment of heart failure. Dofetilide at less than or equal to 3 x 10(-5) m had no effect on the quiescent Wistar Kyoto (WKY) rat aorta, mesenteric and intralobar arteries, or the spontaneous contractions of the WKY rat portal vein. Dofetilide at 10(-6) to 3 x 10(-5) m relaxed the KCl-contracted aorta. Dofetilide at 10(-9)-10(-7) m augmented the force of contraction of left ventricle strips from 12- and 18-month-old WKY rats at 2 Hz. Spontaneously hypertensive rats (SHRs) at 12 and 17-21 months of age are models of cardiac hypertrophy and failure, respectively. The augmentation of force at 2 Hz with dofetilide was similar on 12- and 18-month-old WKY rats and 12-month-old SHRs but reduced on the 18-month-old SHR left ventricle. At a higher more physiological frequency, 4 Hz, the threshold concentration of dofetilide required to augment the force responses of 21-month-old SHR left ventricles was markedly increased and the maximum augmenting effect was decreased. Dofetilide at 10(-7)-10(-5) m reduced the rate of the 17-month-old WKY rat right atrium, and had a similar effect on age-matched SHR right atrium. In summary, dofetilide is a positive inotrope and negative chronotrope in the rat. However, as the positive inotropic effect is not observed with clinically relevant concentrations at a physiological rate in heart failure, dofetilide is unlikely to be useful as a positive inotrope in the treatment of heart failure.

A DC Voltage-Multiplier Circuit Working as a High-Voltage Pulse Generator

The intensive use of semiconductor devices enabled the development of a repetitive high-voltage pulse-generator topology from the dc voltage-multiplier (VM) concept. The proposed circuit is based on an odd VM-type circuit, where a number of dc capacitors share a common connection with different voltage ratings in each one, and the output voltage comes from a single capacitor. Standard VM rectifier and coupling diodes are used for charging the energy-storing capacitors, from an ac power supply, and two additional on/off semiconductors in each stage, to switch from the typical charging VM mode to a pulse mode with the dc energy-storing capacitors connected in series with the load. Results from a 2-kV experimental prototype with three stages, delivering a 10-mu s pulse with a 5-kHz repetition rate into a resistive load, are discussed. Additionally, the proposed circuit is compared against the solid-state Marx generator topology for the same peak input and output voltages.

Repetitive Solid State Pulse Modulator Based on a DC Voltage Multiplier

A newly developed solid-state repetitive high-voltage (HV) pulse modulator topology created from the mature concept of the d.c. voltage multiplier (VM) is described. The proposed circuit is based in a voltage multiplier type circuit, where a number of d.c. capacitors share a common connection with different voltage rating in each one. Hence, besides the standard VM rectifier and coupling diodes, two solid-state on/off switches are used, in each stage, to switch from the typical charging VM mode to a pulse mode with the d.c. capacitors connected in series with the load. Due to the on/off semiconductor configuration, in half-bridge structures, the maximum voltage blocked by each one is the d.c. capacitor voltage in each stage. A 2 kV prototype is described and the results are compared with PSPICE simulations.

Projecto e implementação de um sistema de alimentação para um transformador de alta tensão

Neste trabalho pretende-se estudar, dimensionar e implementar experimentalmente de um sistema de alimentação para transformadores de alta tensão a alta frequência. Este sistema será constituído por dois elementos principais, um rectificador monofásico em ponte totalmente controlado e por um inversor de tensão. Inicialmente realizou-se um estudo sobre as diferentes topologias possíveis para o rectificador considerando diferentes tipos de carga. Realizou-se, também, um estudo sobre o circuito de geração dos impulsos de disparo dos tiristores, executado com base num circuito integrado TCA 785, dimensionou-se os elementos constituintes do circuito de disparo, e de um sistema de controlo da tensão de saída do rectificador. Posteriormente estudou-se o funcionamento do inversor de tensão, definindo-se os modos de operação e dimensionou-se um circuito ressonante tendo em conta os parâmetros construtivos do transformador que se pretende utilizar. Finalmente procedeu-se à implementação prática dos sistemas previamente dimensionados e simulados e à apresentação dos respectivos resultados.

Monitorização integrada para sistemas de alimentação distribuídos

Mestrado em Engenharia Electrotécnica e de Computadores

Controlo directo de binário de uma máquina assíncrona trifásica

Dissertação para obtenção do grau de Mestre em Engenharia Electrotécnica Ramo de Automação e Electrónica Industrial

Projecto, montagem e teste de uma unidade modular de detecção de radiação Geiger-Muller

Dissertação para obtenção do grau de Mestre em Engenharia Electrotécnica Ramo de Automação e Electrónica Industrial