The interrelations among stochastic pacing, stability, and memory in the heart.
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ABSTRACT:
SUBMITTER: Dvir H
PROVIDER: S-EPMC4142253 | biostudies-literature | 2014 Aug
REPOSITORIES: biostudies-literature
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Project description:The restitution properties of cardiac action potential duration (APD) and conduction velocity (CV) are important factors in arrhythmogenesis. They determine alternans, wavebreak, and the patterns of reentrant arrhythmias. We developed a novel approach to characterize restitution using transfer functions. Transfer functions relate an input and an output quantity in terms of gain and phase shift in the complex frequency domain. We derived an analytical expression for the transfer function of interbeat intervals (IBIs) during conduction from one site (input) to another site downstream (output). Transfer functions can be efficiently obtained using a stochastic pacing protocol. Using simulations of conduction and extracellular mapping of strands of neonatal rat ventricular myocytes, we show that transfer functions permit the quantification of APD and CV restitution slopes when it is difficult to measure APD directly. We find that the normally positive CV restitution slope attenuates IBI variations. In contrast, a negative CV restitution slope (induced by decreasing extracellular [K(+)]) amplifies IBI variations with a maximum at the frequency of alternans. Hence, it potentiates alternans and renders conduction unstable, even in the absence of APD restitution. Thus, stochastic pacing and transfer function analysis represent a powerful strategy to evaluate restitution and the stability of conduction.
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Project description:The variation of and the interrelation between different energy markets significantly affect the competitiveness of various energy technologies, therefore complicate the decision-making problem for a complex energy system consisting of multiple competing technologies, especially in a long-term time frame. The interrelations between these markets have not been accounted for in the existing energy system modelling efforts, leading to a distortion of understanding of the market impact on the technological choices and operations in the real world. This study investigates the strategic and operational decision-making problem for such an energy system characterized by three competing technologies from crude oil, natural gas, and coal. A stochastic programming model is constructed by incorporating multiple volatile energy prices interrelated with each other. Oil price is modelled by the mean-reverting Ornstein-Uhlenbeck process and serves as the exogenous variable in the ARIMAX models for natural gas and downstream plastic prices. The K-means clustering method is employed to extract a handful of distinctive patterns from a large number of simulated price projections to enhance the computing efficiency without losing retaining critical information and insights from the price co-movement. The model results suggest that the high volatility of the energy market weakens the possibility of selecting the corresponding technology. The oil-based route, for example, gradually loses its market share to the coal approach, attributed to a higher volatile oil market. The proposed method is applicable to other problems of the same kind with high-dimensional stochastic variables.Supplementary informationThe online version contains supplementary material available at 10.1007/s10479-021-04229-3.
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Project description:Light has been used to noninvasively alter the excitability of both neural and cardiac tissue 1-10. Recently, pulsed laser light has been shown to be capable of eliciting action potentials in peripheral nerves and in cultured cardiomyocytes 7-10. Here, we demonstrate for the first time optical pacing (OP) of an intact heart in vivo. Pulsed 1.875 ?m infrared laser light was employed to lock the heart rate to the pulse frequency of the laser. A laser Doppler velocimetry (LDV) signal was used to verify the pacing. At low radiant exposures, embryonic quail hearts were reliably paced in vivo without detectable damage to the tissue, indicating that OP has great potential as a tool to study embryonic cardiac dynamics and development. In particular, OP can be utilized to control the heart rate, and thereby alter stresses and mechanically transduced signaling.
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Project description:Optical pacing has been demonstrated to be a viable alternative to electrical pacing in embryonic hearts. In this study, the feasibility of optically pacing an adult rabbit heart was explored. Hearts from adult New Zealand White rabbits (n = 9) were excised, cannulated and perfused on a modified Langendorff apparatus. Pulsed laser light (λ = 1851 nm) was directed to either the left or right atrium through a multimode optical fiber. An ECG signal from the left ventricle and a trigger pulse from the laser were recorded simultaneously to determine when capture was achieved. Successful optical pacing was demonstrated by obtaining pacing capture, stopping, then recapturing as well as by varying the pacing frequency. Stimulation thresholds measured at various pulse durations suggested that longer pulses (8 ms) had a lower energy capture threshold. To determine whether optical pacing caused damage, two hearts were perfused with 30 µM of propidium iodide and analyzed histologically. A small number of cells near the stimulation site had compromised cell membranes, which probably limited the time duration over which pacing was maintained. Here, short-term optical pacing (few minutes duration) is demonstrated in the adult rabbit heart for the first time. Future studies will be directed to optimize optical pacing parameters to decrease stimulation thresholds and may enable longer-term pacing.
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Project description:Electrical restitution (ER) is a major determinant of repolarization stability and, under fast pacing rate, it reveals memory properties of the cardiac action potential (AP), whose dynamics have never been fully elucidated, nor their ionic mechanisms. Previous studies have looked at ER mainly in terms of changes in AP duration (APD) when the preceding diastolic interval (DI) changes and described dynamic conditions where this relationship shows hysteresis which, in turn, has been proposed as a marker of short-term AP memory and repolarization stability. By means of numerical simulations of a non-propagated human ventricular AP, we show here that measuring ER as APD versus the preceding cycle length (CL) provides additional information on repolarization dynamics which is not contained in the companion formulation. We focus particularly on fast pacing rate conditions with a beat-to-beat variable CL, where memory properties emerge from APD vs CL and not from APD vs DI and should thus be stored in APD and not in DI. We provide an ion-currents characterization of such conditions under periodic and random CL variability, and show that the memory stored in APD plays a stabilizing role on AP repolarization under pacing rate perturbations. The gating kinetics of L-type calcium current seems to be the main determinant of this safety mechanism. We also show that, at fast pacing rate and under otherwise identical pacing conditions, a periodically beat-to-beat changing CL is more effective than a random one in stabilizing repolarization. In summary, we propose a novel view of short-term AP memory, differentially stored between systole and diastole, which opens a number of methodological and theoretical implications for the understanding of arrhythmia development.
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Project description:BackgroundLeft bundle branch pacing (LBBP) has emerged as an alternative to biventricular pacing (BVP) for delivering cardiac resynchronization therapy. We sought to compare the acute improvement of electrical and mechanical synchrony, and hemodynamics between LBBP and BVP in patients with heart failure and left bundle branch block.MethodsLBBP and BVP were performed and compared in a crossover fashion in patients with heart failure and left bundle branch block undergoing cardiac resynchronization therapy implantation. Electrical synchrony was assessed by QRS duration and area, mechanical synchrony by the SD of time to peak velocity of 12 left ventricular segments (Ts-SD) and interventricular mechanical delay, and hemodynamics by the maximum rate of left ventricular pressure rise (dP/dtmax).ResultsTwenty-one patient with heart failure and left bundle branch block (mean age 67±10 years, 48% male, and 90% nonischemic cause) were included. Both LBBP and BVP provided significant improvements in electrical and mechanical synchrony, and hemodynamics compared to the baseline. Compared with BVP, LBBP achieved a larger reduction in QRS duration (-11 ms [95% CI, -17 to -4 ms]; P=0.003) and QRS area (-85 µVs [95% CI, -113 to -56 µVs]; P<0.001); LBBP achieved a greater decrease in Ts-SD (-14 ms [95% CI, -21 to -7 ms]; P=0.001), with no significant difference in interventricular mechanical delay (-2 ms [95% CI, -13 to 8 ms]; P=0.63). The increase in dP/dtmax from LBBP was significantly higher than that from BVP (6% [95% CI, 2%-9%]; P=0.002).ConclusionsLBBP delivers greater acute electrical and mechanical resynchronization and hemodynamic improvement than BVP in predominantly nonischemic heart failure patients with left bundle branch block.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT04505384.
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Project description:CMV is an obligate and persistent intracellular pathogen that continually drives the production of highly differentiated virus-specific CD8+ T cells in an Ag-dependent manner, a phenomenon known as memory inflation. Extensive proliferation is required to generate and maintain inflationary CD8+ T cell populations, which are counterintuitively short-lived and typically exposed to limited amounts of Ag during the chronic phase of infection. An apparent discrepancy therefore exists between the magnitude of expansion and the requirement for ongoing immunogenic stimulation. To address this issue, we explored the clonal dynamics of memory inflation. First, we tracked congenically marked OT-I cell populations in recipient mice infected with murine CMV (MCMV) expressing the cognate Ag OVA. Irrespective of numerical dominance, stochastic expansions were observed in each population, such that dominant and subdominant OT-I cells were maintained at stable frequencies over time. Second, we characterized endogenous CD8+ T cell populations specific for two classic inflationary epitopes, M38 and IE3. Multiple clonotypes simultaneously underwent Ag-driven proliferation during latent infection with MCMV. In addition, the corresponding CD8+ T cell repertoires were stable over time and dominated by persistent clonotypes, many of which also occurred in more than one mouse. Collectively, these data suggest that stochastic encounters with Ag occur frequently enough to maintain oligoclonal populations of inflationary CD8+ T cells, despite intrinsic constraints on epitope display at individual sites of infection with MCMV.
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