No description available.

T-type Ca²+ channels (TTCCs) are expressed in cardiac pacemaker cells and conduction system of mammals. However, the roles of TTCCs in heart rate (HR) generation and regulation, and arrhythmias are not well understood. In the mouse, the major TTCC expressed in the heart is Cav3.1/a1G, and therefore we used Cav3.1/ 1G transgenic (TG) and knockout (KO) mice respectively to define the role of TTCC in the heart rate generation, regulation and arrhythmias. Telemetric (conscious) and surface (anesthetized) electrocardiogram (ECG) were used to determine the baseline HR and the effect of isoproterenol (ISO) on the HR in vivo. To reduce the complication of in vivo HR regulation, Langendorff ECG (a technique to record ECG from the surface of Langendorff-perfused, spontaneously-beating, mouse hearts) was used to measure HR at baseline and after ISO stimulation. The basal firing rates and ISO-induced dose-response on the firing rate of sinoatrial nodal cells (SANCs) were studied. Whole cell voltage clamp was used to study the effects of ISO on ICa-L and ICa-T and the underlying mechanism with ventricular myocytes of 1G DTG (Cav3.1/a1G double transgenic) mice. The ICa-T before and after ISO application on a1G DTG, KO and control SAN cells were also measured. At baseline, telemetric ECG ( a technique to record ECG by a wireless ambulatory central monitoring system from the implanted transmitters) recording showed no significant difference in HR between the Cav3.1/a1G TG mice, Cav3.1/a1G KO mice and control mice. ISO increased the HR in conscious mice to the same extent in both DTG and KO mice. However, when the central nervous system regulation is depressed (anesthetized) or removed (ex-vivo Langendorff perfusion), the percentage of HR increase after ISO application was significantly enhanced in the TG mice but reduced in the KO mice. At the cellular level, both at baseline and under all different ISO concentrations, Cav3.1/a1G KO SANCs had significantly slower firing rates than those of control SANCs. ISO induced smaller beating rate increase in Cav3.1/a1G KO than in C57BL/6 control mice. Cav3.1/a1G DTG SANCs have similar firing rates as those of control SANCs at baseline. At a low ISO concentration (10-9M), the beating rate increase induced by ISO in Cav3.1/a1G DTG SANCs is a little higher but not significant than that in FVB control SANCs. However, at higher ISO concentrations (10-8 and 10-7 M), ISO induced more increases in beating rate in Cav3.1/a1G DTG SANCs than in FVB control SANCs. In DTG mice, the enhanced increase of heart rate by ISO, a ß-adrenergic agonist, is due to the upregulation of the activity of Cav3.1/a1G. The upregulation of Cav3.1/a1G activity is through protein kinase A (PKA). Db-cAMP, a PKA activator, can greatly increase the T-type calcium current (ICa-T), and H89, a PKA inhibitor, blocks ISO effect on ICa-L and ICa-T in Cav3.1/a1G DTG ventricular myocytes, ISO also significantly increases Cav3.1/1G T-type Ca²+ currents in sinoatrial nodal cells. In telemetric ECG recordings, the data showed that inactivation of Cav3.1/a1G increases the incidence of AVB (atrioventricular block, impaired conduction or blocking of the impulse at the level of the atrioventricular junction, resulting in a lack of electrical and/or mechanical coordination between the atria and the ventricles) after ISO application compared to control mice. In addition, there are more PVB (premature ventricular beat, the heartbeat that is initiated by the heart ventricles rather than by the sinoatrial node) observed in Langendorff ECG in Cav3.1/a1G KO mice after ISO application. In conclusion, Cav3.1/a1G TTCC might play important roles in basal HR generation and in sympathetic/adrenergic regulation of HR, in which PKA could be an important mediator. Ablation of Cav3.1/a1G increases the susceptibility of arrhythmia after ISO application. / Physiology

No / In 2005, the UK Department of Health recommended that a new role, the arrhythmia care coordinator (ACC), be created to guide patients through the diagnosis and treatment for arrhythmia. The belief was that this would improve the efficiency of care and improve their quality of life. The British Heart Foundation provided funding for 32 such posts, all of which were filled by arrhythmia specialist nurses, and commissioned an evaluation of the new service to assess its impact on patients. This paper focuses on the impact of the ACCs on their patients’ levels of anxiety and depression, hospital readmissions and costs to the National Health Service (NHS). From 2008 to 2010, using questionnaires, we conducted a longitudinal audit of the psychological status of the patients referred to the ACCs; we also assessed the ACCs’ impact on readmissions and cost benefits to the NHS using UK Hospital Episode Statistics. We found high levels of anxiety and depression amongst patients. Nearly one-third were at the ‘borderline’ or ‘clinically anxious’ and 18% were at the ‘borderline’ or ‘clinically depressed’ level at their first assessment with small changes at follow-up. In arrhythmia specialist nurse sites, readmission rates were reduced by half. After deducting the cost of the ACCs and their support, the estimated annual saving was £29,357 per ACC. This evaluation has shown that the NHS saves £29,357 per year over and above the costs of employing a British Heart Foundation ACC and that all arrhythmia centres should be encouraged to employ an appropriate number of such specialists.

Diss. (sammanfattning) Umeå : Univ., 2007. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

No description available.

published_or_final_version / abstract / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy

Stretch is known to result in an electrically less stable ventricular substrate, yet the reported effects of stretch on measured electrophysiological parameters have been inconsistent and even contradictory. The goal of this study was to evaluate the effects of acute mechanical stretch on cardiac electrical features thought to be key in generation of arrhythmia, namely restitution of action potential duration (APD), electrical memory, and onset of alternans. Microelectrodes were used to record intracellular potentials pre, during, and post-stretch from isolated right ventricular tissues from swine. In separate experiments, the effects of two levels of stretch were quantified. Pacing protocols employing explicit diastolic interval (DI) control and cycle length (CL) control were used to obtain measures of restitution of APD, memory, and alternans of APD. Stretching the tissue had varying effects on APD, restitution and memory. Stretch increased APD, restitution slopes and memory by as much as 24, 30 and 53 % in some cases, while it decreased these by up to 18, 37 and 81 % in others. During stretch, alternans of APD were observed in some cases, which occurred at slower rates of activation than before stretch. Histology of tissue samples showed localized changes in orientation of cells relative to the direction of stretch. Our results show that among individual trials, stretch altered the measured electrophysiological properties, sometimes markedly. However, when pooled together, these changes cancelled each other and the averages showed no statistically significant difference after stretch. A potential mechanism that explains this divergent and inconsistent response to stretch is the presence of local, micron level, variation in orientation of myocytes. Upon stretch, these divergent effects likely increase dispersion of repolarization diffusely and might thus be the reason behind the consistently observed increase in arrhythmic substrate after stretch.

Acousto-electric (AE) effect comes from an interaction between electrical current and acoustic pressure generated when acoustic waves travel through a conducting material. It currently has two main application areas, ultrasound current source density imaging (UCSDI) and AE hydrophone. UCSDI can detect the current direction by modulating the dipole field with ultrasound pulse, and it is now used to form 3D imaging of dipole changing in one period of treatment, such as arrhythmia in the heart and epilepsy in the brain. As ultrasound pulse passes through electrical field, it convolutes or correlates with the inner product of the electric fields formed by the dipole and detector. The polarity of UCSDI is not determined by Doppler effect that exists in pulse echo (PE) signal, but the gradient of lead field potentials created by dipole and recording electrode, making the base-banded AE voltage positive at the anode and negative at cathode. As convolution shifts spectrum lower, the base band frequency for polarity is different from the center frequency of AE signal. The simulation uses the principles of UCSDI, and helps to understand the phenomena in the experiment. 3-D Fast Fourier Transform accelerates the computing velocity to resolve the correlation in the simulation of AE signal. Most single element hydrophones depend on a piezoelectric material that converts pressure changes to electricity. These devices, however, can be expensive, susceptible to damage at high pressure, and/or have limited bandwidth and sensitivity. An AE hydrophone requires only a conductive material and can be constructed out of common laboratory supplies to generate images of an ultrasound beam pattern consistent with more expensive hydrophones. Its sensitivity is controlled by the injected bias current, hydrophone shape, thickness and width of sensitivity zone. The design of this device needs to be the tradeoff of these parameters. Simulations were made to optimize the design with experimental validation using specifically fabricated devices composed of a resistive element of indium tin oxide (ITO).

Electrocardiography (ECG or EKG) is the process of recording the electrical activity of the heart over a period of time using electrodes placed on a patient’s body. These electrodes detect the tiny electrical changes on the skin that arise from the heart muscle depolarizing during each heartbeat. [1] It is necessary for the diagnosis and prompt initiation of therapy in patients with acute coronary syndromes (ACS) and is the most accurate means of diagnosing conduction disturbances and arrhythmias. [2]ECG is an irreplaceable diagnostic method in clinical practice. It offers great diagnostic value at minimal costs while being a relatively quick, painless and noninvasive process. The quality of the resulting graph is depending on the accurate placement of the electrodes on the patients' body and that the patient lies absolutely still to avoid any muscle contractions which may lead to distortions of the graph.The interpretation of ECGs is a highly complex topic which requires lots of training and experience. Although there has been plenty of research on the topic of automated interpretation and pattern recognition of ECGs by computer algorithms and neural networks, a reliable interpretation of complex ECGs cannot be guaranteed as of today. While the trend seems to favor automated ECG interpretation, a clear prediction when these technologies have saturated the market cannot be given. One reason for this, similar to autonomous vehicles, is the issue of where liability can be found when an incorrect diagnosis leads to harming of a patient. For the foreseeable future we will most likely rely on the skill and experience of humans to interpret ECGs. [1] https://en.wikipedia.org/wiki/Electrocardiography [2] The British Journal of Primary Care Nursing: Taking an ECG: Getting the best possible recording