Background: Modulation of ischemia-dependent pathways alters electrophysiological evolution of ventricular fibrillation(VF). Hypothesis: 1)There is regional disease-related expression of KATP-channels in human cardiomyopathic hearts. 2)KATP-channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness(ΔERP). Methods and Results: Electric mapping of control(n=6) and treatment(n=9) (10 μmol/L glibenclamide) isolated human cardiomyopathic hearts was performed. Spontaneous defibrillation and KATP-subunit gene expression were studied. Spontaneous VF termination occurred in 1/6 control and 7/8 treated hearts (P=0.026). After 180 seconds of ischemia, LV transmural dispersion in VF cycle length was observed(p=0.001), which was attenuated by glibenclamide. There was greater gene expression of all KATP-subunit on the endocardium compared with the epicardium(P<0.02). In ischemic rat heart model, ΔERP was verified with pacing protocols (36±5ms vs 4.9±4ms, p=0.019). Conclusions: KATP channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of KATP channels promotes spontaneous defibrillation by attenuating ischemia-dependent ΔERP during VF.

Background: Modulation of ischemia-dependent pathways alters electrophysiological evolution of ventricular fibrillation(VF). Hypothesis: 1)There is regional disease-related expression of KATP-channels in human cardiomyopathic hearts. 2)KATP-channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness(ΔERP). Methods and Results: Electric mapping of control(n=6) and treatment(n=9) (10 μmol/L glibenclamide) isolated human cardiomyopathic hearts was performed. Spontaneous defibrillation and KATP-subunit gene expression were studied. Spontaneous VF termination occurred in 1/6 control and 7/8 treated hearts (P=0.026). After 180 seconds of ischemia, LV transmural dispersion in VF cycle length was observed(p=0.001), which was attenuated by glibenclamide. There was greater gene expression of all KATP-subunit on the endocardium compared with the epicardium(P<0.02). In ischemic rat heart model, ΔERP was verified with pacing protocols (36±5ms vs 4.9±4ms, p=0.019). Conclusions: KATP channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of KATP channels promotes spontaneous defibrillation by attenuating ischemia-dependent ΔERP during VF.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(論文) 学位授与年月日:平成4年10月19日 狩野良雄氏の博士論文として提出された

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 113-118). Available also in a digital version from Dissertation Abstracts.

Thesis (M.S.)--University of Akron, Dept. of Biomedical Engineering, 2008. / "December, 2008." Title from electronic thesis title page (viewed 12/12/2009) Advisor, Dale H. Mugler; Committee members, Daniel B. Sheffer, Bruce C. Taylor; Department Chair, Daniel B. Sheffer; Dean of the College, George K. Haritos; Dean of the Graduate School, George R. Newkome. Includes bibliographical references.

Thesis (M.S.)--Brigham Young University. Dept. of Mechanical Engineering, 2003. / Includes bibliographical references (p. 105-107).

Previous investigations have demonstrated that reactive oxygen species such as hydrogen peroxide (H2O2) have the ability to alter electrophysiological and mechanical properties of rat ventricular cardiac myocytes. However, despite the breadth of the literature, there is little definitive consensus on the cellular mechanisms. The purpose of this study, therefore, was to study the cellular mechanism of action of H2O2 and test whether H2O2-mediated affects were partially a result of reverse-mode Na+/Ca2+ exchanger (NCX) activity. Unloaded cell shortening, intracellular Ca2+ transients, caffeine-induced Ca2+ transients, L-type Ca2+ channel recordings, and action potential waveforms were recorded in the presence of combinations of different compounds including Cd2+, H2O2, and KB-R7943. H2O2 was found to cause significant positive inotropy by an increase in contractility of 80 ± 20 % (n=6) and an increased amplitude of Ca2+ transients by 24 ± 14 % (n=8), relative to pre-treatment values. Interestingly, H2O2 caused an increase in contractility even in the presence of Cd2+ block from 4 ± 1 % (n=9) to 15 ± 3 % (n=5) of resting cell length. Using caffeine pulse experiments to induce unloading of the sarcoplasmic reticulum (SR), we found that 100µM H2O2 did not significantly alter SR Ca2+ load. Under control conditions, H2O2 significantly increased L-type Ca2+ currents while this H2O2-induced increase was not observed in myocytes pretreated with Cd2+. Positive inotropy in the presence of H2O2 was blocked using 10µM KB-R7943, a selective reverse-mode inhibitor of the NCX. However, it was found that 10µM KB-R7943 alone altered action potential profile and suppressed normal contraction. Altogether, the major finding of this study is that H2O2 has the ability to enhance myocardial contractility, even under conditions of L-type Ca2+ channel inhibition, through a mechanism that likely involves reverse-mode of the NCX. / Thesis (Master, Physiology) -- Queen's University, 2009-03-31 14:00:34.21

The presented studies investigate dynamics of action potential duration (APD) tobetter understand the underlying mechanism for repolarization alternans.We recorded trans-membrane potentials (TMP) in canine endocardial muscle tissueusing standard glass microelectrode under the control of an explicit diastolic interval (DI)control pacing protocol, i.e. feedback protocol. During sequential sinusoidal DI activation,the trajectory of APD dynamics has multiple values of APD correspondent to the sameDI, i.e. restitution is a bi-modal relationship. Our results indicate that: 1) there is a delay,similar to hysteresis, of change in APD responding to change in DI, 2) and the timecourse of the delay is asymmetric for fast or slow pacing history. The alternans wasobserved during constant DI pacing, i.e. the DI preceding each APD was invariant orchanged within a limited range. This finding suggests that alternans of APD do not needthe oscillation of preceding DI, i.e. DI dependent restitution is not a necessary conditionfor the alternans. This result implies that DI independent component exists in themechanism of the alternans. Nonetheless, the amplitude of alternans was statisticallylarger during constant pacing cycle length (PCL) pacing than that during constant DIpacing, even though both PCL and DI pacing trials used similar average activation rate.These results also demonstrate the ability of the feedback protocol to analyze the memoryeffects and dissect different components in the mechanism of alternans.Two computational models, Luo-Rudy dynamics (LRD) and cardiac ventricle model(CVM) were used to study the hysteresis in restitution. By perturbing membrane current:L-type calcium current, rapid and slow potassium rectifier, and intracellular calciumtransfer rate in sarcoplasmic reticulum (SR) and using sinusoidal DI pacing sequence, weshowed that the asymmetric calcium current across the membrane and its interaction withcalcium buffer in SR during increasing and decreasing DI phase plays an important rolein the hysteresis. CVM was used to study the alternans during constant DI pacing.However CVM failed to replicate the alternans that occurred in the experiments. Thisresult implies that CVM lacks the electrophysiological kinetics related to alternans thatwas shown in our experiment.

Pagrindinis darbo tikslas buvo išsiaiškinti, kokie yra dažniausiai pasitaikantys šunų širdies ritmo sutrikimai, kokie pagrindiniai diagnostiniai metodai naudojami aritmijoms nustatyti ir diferencijuoti, bei aprašyti medikamentinius preparatus, naudojamus gydant šunis nuo aritmijų. Darbo metu buvo analizuojami LSMU VA Dr. L. Kiaučeliūno smulkiųjų gyvūnų klinikoje, nuo 2008 iki 2013 metų, surinkti gydytų šunų duomenys, kuriems pasireiškė širdies ritmo sutrikimai. Buvo analizuojami pacientų anamnezės duomenys, kuriuos pateikė gyvūnų savininkai, ieškoma aritmijų pasireiškimo priklausomybių nuo šunų lyties, veislės, amžiaus, kilmės, svorio. Širdies ritmo sutrikimai buvo nustatyti 145 šunims, iš kurių 103 buvo patinai ir 42 patelės. Širdies ritmo sutrikimai buvo diagnozuojami auskultuojant širdies darbą, atliekant echokardiografiją, rentgeninį tyrimą bei užrašant elektrokardiogramą – tai yra pagrindinis aritmijų tyrimo metodas. Buvo nustatyta, jog dažniausiai pasitaikantis širdies ritmo sutrikimas šunims yra sinusinės aritmijos, kurios pasireiškė 61 pacientui, tai sudarė 42 proc. šunų, kuriems buvo nustatytos aritmijos. Be sinusinių aritmijų, tiriamojoje šunų grupėje, buvo nustatyti dar 6 rūšių širdies ritmo sutrikimai: supraventrikulinės ekstrasistolijos buvo diagnozuotos 21 (14,5 proc.) šuniui, ventrikulinės ekstrasistolijos – 34 (23,4 proc.), Hiso pluošto kojyčių blokados – 9 (6,2 proc.), Io AV blokados – 10 (6,9 proc.), IIo AV blokados – 6 (4,1 proc.), o IIIo AV blokados - 3 (2... [toliau žr. visą tekstą] / The main aim of work – to determine what are the most common canine cardiac rhythm disorders, analyse diagnostic methods and describe basic medical drugs used in the treatment of arrhythmias. Data of dogs morbidity of cardiac rhythm disorders in 2008 – 2013 has been collected at Dr. L. Kriaučeliūnas Small Animal Clinic of Veterinary Academy of Lithuanian University of Health Sciences. Cardiac rhythm disorders have been diagnosed to 145 dogs: 103 of them were males, and 42 – were females. Clinical diagnosis has been approved according to results of diagnostic methods like: auscultation of heart rate and sounds, X-ray, cardioechoscopy and the main diagnostic method of cardiac arrhythmias – EKG. Sinus arrhythmia has been determined as the most common cardiac rhythm disorder of dogs. This type of arrhythmia has been diagnosed to 61 (42 %) dogs. There were more types of arrhytmias diagnosed like: premature ventricular contractions – 34 (23,4 %) cases, premature atrial contractions - 21 (14,5 %) cases, Hiss bundle branch blocks – 9 (6,2 %) cases and AV blocks – 17 (13,1 %) cases (p<0.001). Male dogs were ill with the cardiac rhythm disorders more often compared to females (71,0% vs. 29,0 %). Arrhythmias were diagnosed to 109 (75,2 %) purebred dogs and 36 (24,8 %) mixed breed dogs (p<0.01). Cardiac rhythm disorders have been diagnosed to 13 Rottweilers (11,9%) and 11 German Shepherds (10,0%), which were most common breeds (p<0.01). In addition, dogs from eight years old and older... [to full text]

Atrial fibrillation (AF) is a complex, multifaceted arrhythmia. Pathogenesis of AF is associated with multiple aetiologies and the mechanisms by which it is sustained and perpetuated are similarly diverse. In particular, regional heterogeneity in the electrophysiological properties of normal and pathological tissue plays a critical role in the occurrence of AF. Understanding AF in the context of electrophysiological heterogeneity requires cell-specific ionic models of electrical activity which can then be incorporated into models on larger temporal and spatial scales. Biophysically-based models have typically dominated the study of cellular excitability providing detailed and precise descriptions in the form of complex mathematical formulations. However, such models have limited applicability in multidimensional simulations as the computational expense is too prohibitive. Simplified mathematical models of cardiac cell electrical activity are an alternative approach to these traditional biophysically-detailed models. Utilizing this approach enables the embodiment of cellular excitation characteristics at minimal computational cost such that simulations of arrhythmogensis in atrial tissue are conceivable. In this thesis, a simplified, generic mathematical model is proposed that characterizes and reproduces the action potential waveforms of individual cardiac myocytes. It incorporates three time-dependent ionic currents and an additional time-independent leakage current. The formulation of the three time-dependent ionic currents is based on 4-state Markov schemes with state transition rates expressed as nonlinear sigmoidal functions of the membrane potential. Parameters of the generic model were optimized to fit the action potential waveforms of the Beeler-Reuter model, and, experimental recordings from atrial and sinoatrial cells of rabbits. A nonlinear least-squares optimization routine was employed for the parameter fits. The model was successfully fitted to the Beeler-Reuter waveform (RMS error: 1.4999 mV) and action potentials recorded from atrial tissue (RMS error: 1.3398 mV) and cells of the peripheral (RMS error: 2.4821 mV) and central (RMS error: 2.3126 mV) sinoatrial node. Thus, the model presented here is a mathematical framework by which a wide variety of cell-specific AP morphologies can be reproduced. Such a model offers the potential for insights into possible mechanisms that contribute to heterogeneity and/or arrhythmia.