Desynchronization in a cardiac resynchronization device induced by a pacemaker-mediated tachycardia algorithm

This report describes the occurrence of desynchronization in a patient with a cardiac resynchronization device programmed with an active pacemaker-mediated tachycardia algorithm based on AV delay modification. Desynchronization was precipitated by sinus tachycardia and the abrupt return of the prevailing AV delay that followed the periodic prolongation of the AV delay mandated by activity of the algorithm. Prevention of desynchronization in this setting requires programming a right ventricular upper rate interval longer than the sum of the programmed ventriculoatrial interval and the AV delay.     

Utility of cardiac imaging in patients with ventricular tachycardia

Ventricular tachycardia (VT) is a life-threatening arrhythmia that may be idiopathic or result from structural heart disease. Cardiac imaging is critical in the diagnostic workup and risk stratification of patients with VT. Data gained from cardiac imaging provides information on likely mechanisms and sites of origin, as well as risk of intervention. Pre-procedural imaging can be used to plan access route(s) and identify patients where post-procedural intensive care may be required. Integration of cardiac imaging into electroanatomical mapping systems during catheter ablation procedures can facilitate the optimal approach, reduce radiation dose, and may improve clinical outcomes. Intraprocedural imaging helps guide catheter position, target substrate, and identify complications early. This review summarises the contemporary imaging modalities used in patients with VT, and their uses both pre-procedurally and intra-procedurally.     

具有时滞的一捕食者-两食饵比率型生态系统的持久性与稳定性

研究一个具有时滞的一捕食者－两食饵比率型生态系统,证明了该系统在适当条件下的一致持久性。通过构造Lyapunov泛函,得到了该系统正平衡点局部渐近稳定的充分条件。     

Effects of early afterdepolarizations on reentry in cardiac tissue: a simulation study

Early afterdepolarizations (EADs) are classically generated at slow heart rates when repolarization reserve is reduced by genetic diseases or drugs. However, EADs may also occur at rapid heart rates if repolarization reserve is sufficiently reduced. In this setting, spontaneous diastolic sarcoplasmic reticulum (SR) Ca release can facilitate cellular EAD formation by augmenting inward currents during the action potential plateau, allowing reactivation of the window L-type Ca current to reverse repolarization. Here, we investigated the effects of spontaneous SR Ca release-induced EADs on reentrant wave propagation in simulated one-, two-, and three-dimensional homogeneous cardiac tissue using a version of the Luo-Rudy dynamic ventricular action potential model modified to increase the likelihood of these EADs. We found: 1) during reentry, nonuniformity in spontaneous SR Ca release related to subtle differences in excitation history throughout the tissue created adjacent regions with and without EADs. This allowed EADs to initiate new wavefronts propagating into repolarized tissue; 2) EAD-generated wavefronts could propagate in either the original or opposite direction, as a single new wave or two new waves, depending on the refractoriness of tissue bordering the EAD region; 3) by suddenly prolonging local refractoriness, EADs caused rapid rotor displacement, shifting the electrical axis; and 4) rapid rotor displacement promoted self-termination by collision with tissue borders, but persistent EADs could regenerate single or multiple focal excitations that reinitiated reentry. These findings may explain many features of Torsades des pointes, such as perpetuation by focal excitations, rapidly changing electrical axis, frequent self-termination, and occasional degeneration to fibrillation.     

Ventricular tachycardia in the setting of a large cardiac fibroma in a pediatric patient

Ventricular tachycardia and cardiac tumors are both extremely rare diagnoses in pediatric patients. We report a pediatric case of cardiac fibroma that was noted during the work up of ventricular tachycardia in a young patient concomitantly diagnosed with severe acute respiratory syndrome coronavirus 2.     

具有时滞的Hopfield人工神经网络动力系统模型的全局渐近稳定性

Hopfield人工神经网络动力系统模型平衡点的全局渐近稳定性在网络记忆以及最优化等领域具有广泛的应用。本文中,作者研究了一类具有时滞的Hopfield人工神经网络动力系统,通过构造Liapunov泛函的方法,获得了其平衡点全局渐近稳定和局部渐近稳定的充分判定条件。所给出的判定条件只依赖于系统本身的拳数参数和传递函数以及系统中出现的部分时滞。同时,当系统的自身反馈项为负时,此自身反馈项对于系统的稳定性起到稳定化的作用。此外,数值模拟表明时滞的变化对于系统的稳定性具有重要的影响。可破坏系统的稳定性。进而产生周期振动或更为复杂的非线性现象。     

Complex temporal patterns of spontaneous initiation and termination of reentry in a loop of cardiac tissue

A two-component model is developed consisting of a discrete loop of cardiac cells that circulates action potentials as well as a pacing mechanism. Physiological properties of cells such as restitutions of refractoriness and of conduction velocity are given via experimentally measured functions. The dynamics of circulating pulses and the pacer's action are regulated by two threshold relations. Patterns of spontaneous initiations and terminations of reentry (SITR) generated by this system are studied through numerical simulations and analytical observations. These patterns can be regular or irregular; causes of irregularities are identified as the threshold bistability (T-bistability) of reentrant circulation and in some cases, also phase-resetting interactions with the pacer.     

Role of matricellular proteins in cardiac tissue remodeling after myocardial infarction

After onset of myocardial infarction (MI), the left ventricle (LV) undergoes a continuum of molecular, cellular, and extracellular responses that result in LV wall thinning, dilatation, and dysfunction. These dynamic changes in LV shape, size, and function are termed cardiac remodeling. If the cardiac healing after MI does not proceed properly, it could lead to cardiac rupture or maladaptive cardiac remodeling, such as further LV dilatation and dysfunction, and ultimately death. Although the precise molecular mechanisms in this cardiac healing process have not been fully elucidated, this process is strictly coordinated by the interaction of cells with their surrounding extracellular matrix (ECM) proteins. The components of ECM include basic structural proteins such as collagen, elastin and specialized proteins such as fibronectin, proteoglycans and matricellular proteins. Matricellular proteins are a class of non-structural and secreted proteins that probably exert regulatory functions through direct binding to cell surface receptors, other matrix proteins, and soluble extracellular factors such as growth factors and cytokines. This small group of proteins, which includes osteopontin, thrombospondin-1/2, tenascin, periostin, and secreted protein, acidic and rich in cysteine, shows a low level of expression in normal adult tissue, but is markedly upregulated during wound healing and tissue remodeling, including MI. In this review, we focus on the regulatory functions of matricellular proteins during cardiac tissue healing and remodeling after MI.     

Considerations for the use of cellular electrophysiology models within cardiac tissue simulations

The use of mathematical models to study cardiac electrophysiology has a long history, and numerous cellular scale models are now available, covering a range of species and cell types. Their use to study emergent properties in tissue is also widespread, typically using the monodomain or bidomain equations coupled to one or more cell models. Despite the relative maturity of this field, little has been written looking in detail at the interface between the cellular and tissue-level models. Mathematically this is relatively straightforward and well-defined. There are however many details and potential inconsistencies that need to be addressed, in order to ensure correct operation of a cellular model within a tissue simulation. This paper will describe these issues and how to address them.Simply having models available in a common format such as CellML is still of limited utility, with significant manual effort being required to integrate these models within a tissue simulation. We will thus also discuss the facilities available for automating this in a consistent fashion within Chaste, our robust and high-performance cardiac electrophysiology simulator.It will be seen that a common theme arising is the need to go beyond a representation of the model mathematics in a standard language, to include additional semantic information required in determining the model’s interface, and hence to enhance interoperability. Such information can be added as metadata, but agreement is needed on the terms to use, including development of appropriate ontologies, if reliable automated use of CellML models is to become common.     

Mechanically induced electrical storm as a complication of cardiac resynchronization therapy: A case report

BackgroundCardiac resynchronization therapy (CRT) has been shown to improve both the functional status and mortality of heart failure patients with left bundle branch block. Multiple recent studies suggest several mechanisms for proarrhythmia associated with CRT device.Case summaryA 51-year-old male with symptomatic non-ischemic cardiomyopathy and no previous history of ventricular arrhythmias underwent placement of a biventricular cardioverter-defibrillator. The patient developed sustained monomorphic ventricular tachycardia (VT) soon after implantation. The VT recurred despite reprogramming to right ventricular only pacing. The electrical storm resolved only after a subsequent discharge from the defibrillator caused inadvertent dislodgement of the coronary sinus lead. No recurrent VT occurred throughout 10-years follow up after urgent coronary sinus lead revision.DiscussionWe describe the first reported case of mechanically induced electrical storm due to the physical presence of the CS lead in a patient with a new CRT-D device. It is important to recognize mechanical proarrhythmia as a potential mechanism of electrical storm, as it may be intractable to device reprogramming. Urgent coronary sinus lead revision should be considered. Further studies on this mechanism of proarrhythmia are needed.     

扩散与时滞有关的单种群植物模型的全局稳定性

研究了具有周期系数及扩散与时滞有关的单种群植物模型,得到了该系统存在全局渐近稳定的正周期解的充分条件,其中该条件依赖时滞与扩散     

Immobilization for carbon ion beam ablation of cardiac structures in a porcine model

IntroductionWhereas hadron therapy of static targets is clinically established, treatment of moving organs remains a challenge. One strategy is to minimize motion of surrounding tissue mechanically and to mitigate residual motion with an appropriate irradiation technique. In this technical note, we present and characterize such an immobilization technique for a novel noncancerous application: the irradiation of small targets in hearts with scanned carbon ion beams in a porcine model for elimination of arrhythmias.Material and methodsA device for immobilization was custom-built. Both for the treatment planning 4D-CT scan and for irradiation, breath-hold at end-exhale was enforced using a remotely-controlled respirator. Target motion was thus reduced to heartbeat only. Positioning was verified by orthogonal X-rays followed by couch shift if necessary. Reproducibility of bony anatomy, diaphragm, and heart position after repositioning and between repeated breath-hold maneuvers was evaluated on X-rays and cardiac-gated 4D-CTs. Treatment was post hoc simulated on sequential 4D-CTs for a subset of animals, after immediate repositioning and after a delay of one week, similar to the delay between imaging and irradiation.ResultsBreath-hold without repositioning was highly reproducible with an RMS deviation of at most one millimeter. 4D-CTs showed larger deformations in soft tissue, but treatment simulation on sequential images resulted in full target coverage (V95 >95%).ConclusionThe method of immobilization permitted reproducible positioning of mobile, thoracic targets for range-sensitive particle therapy. The presented immobilization strategy could be a reasonable approach for future animal investigations with the ultimate goal of translation to therapy in men.     

Effect of delay in a Lotka-Volterra type predator-prey model with a transmissible disease in the predator species

We consider a system of delay differential equations modeling the predator-prey ecoepidemic dynamics with a transmissible disease in the predator population. The time lag in the delay terms represents the predator gestation period. We analyze essential mathematical features of the proposed model such as local and global stability and in addition study the bifurcations arising in some selected situations. Threshold values for a few parameters determining the feasibility and stability conditions of some equilibria are discovered and similarly a threshold is identified for the disease to die out. The parameter thresholds under which the system admits a Hopf bifurcation are investigated both in the presence of zero and non-zero time lag. Numerical simulations support our theoretical analysis.     

Experimental and computational studies of strain–conduction velocity relationships in cardiac tissue

Velocity of electrical conduction in cardiac tissue is a function of mechanical strain. Although strain-modulated velocity is a well established finding in experimental cardiology, its underlying mechanisms are not well understood. In this work, we summarized potential factors contributing to strain–velocity relationships and reviewed related experimental and computational studies. We presented results from our experimental studies on rabbit papillary muscle, which supported a biphasic relationship of strain and velocity under uni-axial straining conditions. In the low strain range, the strain–velocity relationship was positive. Conduction velocity peaked with 0.59 m/s at 100% strain corresponding to maximal force development. In the high strain range, the relationship was negative. Conduction was reversibly blocked at 118±1.8% strain. Reversible block occurred also in the presence of streptomycin. Furthermore, our studies revealed a moderate hysteresis of conduction velocity, which was reduced by streptomycin. We reconstructed several features of the strain–velocity relationship in a computational study with a myocyte strand. The modeling included strain-modulation of intracellular conductivity and stretch-activated cation non-selective ion channels. The computational study supported our hypotheses, that the positive strain–velocity relationship at low strain is caused by strain-modulation of intracellular conductivity and the negative relationship at high strain results from activity of stretch-activated channels. Conduction block was not reconstructed in our computational studies. We concluded this work by sketching a hypothesis for strain-modulation of conduction and conduction block in papillary muscle. We suggest that this hypothesis can also explain uni-axially measured strain–conduction velocity relationships in other types of cardiac tissue, but apparently necessitates adjustments to reconstruct pressure or volume related changes of velocity in atria and ventricles.     

Measuring dose from radiotherapy treatments in the vicinity of a cardiac pacemaker

This study investigated the dose absorbed by tissues surrounding artificial cardiac pacemakers during external beam radiotherapy procedures. The usefulness of out-of-field reference data, treatment planning systems, and skin dose measurements to estimate the dose in the vicinity of a pacemaker was also examined. Measurements were performed by installing a pacemaker onto an anthropomorphic phantom, and using radiochromic film and optically stimulated luminescence dosimeters to measure the dose in the vicinity of the device during the delivery of square fields and clinical treatment plans. It was found that the dose delivered in the vicinity of the cardiac device was unevenly distributed both laterally and anteroposteriorly. As the device was moved distally from the square field, the dose dropped exponentially, in line with out-of-field reference data in the literature. Treatment planning systems were found to substantially underestimate the dose for volumetric modulated arc therapy, helical tomotherapy, and 3D conformal treatments. The skin dose was observed to be either greater or lesser than the dose received at the depth of the device, depending on the treatment site, and so care should be if skin dose measurements are to be used to estimate the dose to a pacemaker. Square field reference data may be used as an upper estimate of absorbed dose per monitor unit in the vicinity of a cardiac device for complex treatments involving multiple gantry angles.     

Reducing the immediate availability of red blood cells in cardiac surgery,a single-centre experience

Background

In our institution, we have redefined our criteria for direct availability of red blood cell (RBC) units in the operation room. In this study, we sought to evaluate the safety of applying this new logistical policy of blood transfusion in the first preliminary group of patients.

Methods

In March 2010, we started a new policy concerning the elective availability of RBC units in the operation room. This policy was called: No Elective Red Cells (NERC) program. The program was applied for patients undergoing primary isolated coronary artery bypass grafting (CABG) or single valve surgery. No elective RBC units were preoperatively ordered for these patients. In case of urgent need, blood was delivered to the operating room within 20 min. The present study includes the first 500 patients who were managed according to this policy. Logistic regression analyses were performed to investigate the impact of biomedical variables on fulfilling this NERC program.

Results

The majority of patients (n = 409, 81 %) did not receive any RBCs during the hospital stay. In patients who did receive RBCs (n = 91, 19 %), 11 patients (2.2 %) received RBCs after 24 h postoperatively. Female gender, left ventricular ejection fraction (LVEF) and EuroSCORE were significant predictors for the need of blood transfusion (OR = 3.12; 2.79; 1.17 respectively).

Conclusion

In a selected group of patients, it is safe to perform cardiac surgery without the immediate availability of RBCs in the operating room. Transfusion was avoided in 81 % of these patients. Female gender, LVEF and EuroSCORE were associated with blood transfusion.     

Chronic cardiac resynchronization therapy and reverse ventricular remodeling in a model of nonischemic cardiomyopathy

While cardiac resynchronization therapy (CRT) has been shown to reduce morbidity and mortality in heart failure (HF) patients, the fundamental mechanisms for the efficacy of CRT are poorly understood. The lack of understanding of these basic mechanisms represents a significant barrier to our understanding of the pathogenesis of HF and potential recovery mechanisms. Our purpose was to determine cellular mechanisms for the observed improvement in chronic HF after CRT. We used a canine model of chronic nonischemic cardiomyopathy. After 15 months, dogs were randomized to continued RV tachypacing (untreated HF) or CRT for an additional 9 months. Six minute walk tests, echocardiograms, and electrocardiograms were done to assess the functional response to therapy. Left ventricular (LV) midmyocardial myocytes were isolated to study electrophysiology and intracellular calcium regulation. Compared to untreated HF, CRT improved HF-induced increases in LV volumes, diameters and mass (p<0.05). CRT reversed HF-induced prolongations in LV myocyte repolarization (p<0.05) and normalized HF-induced depolarization (p<0.03) of the resting membrane potential. CRT improved HF-induced reductions in calcium (p<0.05). CRT did not attenuate the HF-induced increases in LV interstitial fibrosis. Using a translational approach in a chronic HF model, CRT significantly improved LV structure; this was accompanied by improved LV myocyte electrophysiology and calcium regulation. The beneficial effects of CRT may be attributable, in part, to improved LV myocyte function.     

Multistability property in cardiac ionic models of mammalian and human ventricular cells

The underlying mechanisms of irregular cardiac rhythms are still poorly understood. Many experimental and modeling studies are aimed at identifying factors which cause cardiac arrhythmias. However, a lack of understanding of heart rhythm dynamical properties makes it difficult to uncover precise mechanisms of electrical instabilities, and hence to predict the onset of heart rhythm disorders. We review and compare the existing methods of studying cardiac dynamics, including restitution protocol (S1-S2), dynamic restitution protocol and multistability test protocol (S1-CI-S2). We focus on cardiac cell dynamics to elucidate regularities of heart rhythm. We demonstrate the advantages of our newly proposed systematic approach of analysis of cardiac cell dynamics using mammalian Luo Rudy 1991 and human ventricular Ten Tusscher 2006 single cell models under healthy and diseased conditions such as altered K⁺ or Ca²⁺ related currents. We investigate the role of ionic properties and the shape of an action potential on the nonlinear dynamics of electrical processes in periodically stimulated cardiac cells. We show the existence of multistability property for human ventricular cells. Moreover, the multistability is proposed to be an intrinsic property of cardiac cells, and is also suggested to be one of the mechanisms which could underlie the sudden triggering of life-threatening ventricular arrhythmias in the human heart.     

Dephosphorylation of cardiac proteins in vitro - a matter of phosphatase specificity

Protein phosphorylation is reversibly regulated by the interplay between kinases and phosphatases. Recent developments within the field of proteomics have revealed the extent of this modification in nature. To date there is still a lack of information about phosphatase specificity for different proteomes and their conditions to achieve maximum enzyme activity. This information is important per se, and in addition often requested in functional and biochemical in vitro studies, where a dephosphorylated sample is needed as a negative control to define baseline conditions. In this study, we have addressed the effectiveness of two phosphatases endogenously present in the heart (protein phosphatases 1 and 2A) and two generic phosphatases (alkaline phosphatase and lambda protein phosphatase) on three cardiac subproteomes known to be regulated by phosphorylation. We optimized the dephoshorylating conditions on a cardiac tissue fraction comprising cytosolic and myofilament proteins using 2DE and MS. The two most efficient conditions were further investigated on a mitochondrial-enriched fraction. Dephosphorylation of specific proteins depends on the phosphatase, its concentration, as well as sample preparation including buffer composition. Finally, we analyzed the efficiency of alkaline phosphatase, the phosphatase with the broadest substrate specificity, using TiO(2) peptide enrichment and 2DLC-MS/MS. Under these conditions, 95% of the detected cardiac cytoplasmic-enriched phospho-proteome was dephosphorylated. In summary, targeting dephosphorylation of the cardiac muscle subproteomes or a specific protein will drive the selection of the specific phosphatase, and each requires different conditions for optimal performance.     

Spectrally resolved time-correlated single photon counting: a novel approach for characterization of endogenous fluorescence in isolated cardiac myocytes

A new setup for time-resolved fluorescence micro-spectroscopy of cells, based on multi-dimensional time-correlated single photon counting, was designed and tested. Here we demonstrate that the spectrometer allows fast and reproducible measurements of endogenous flavin fluorescence measured directly in living cardiac cells after excitation with visible picosecond laser diodes. Two complementary approaches for the analysis of spectrally- and time-resolved autofluorescence data are presented, comprising the fluorescence decay fitting by exponential series and the time-resolved emission spectroscopy analysis. In isolated cardiac myocytes, we observed three distinct lifetime pools with characteristic lifetime values spanning from picosecond to nanosecond range and the time-dependent red shift of the autofluorescence emission spectra. We compared obtained results to in vitro recordings of free flavin adenine dinucleotide (FAD) and FAD in lipoamide dehydrogenase (LipDH). The developed setup combines the strength of both spectral and fluorescence lifetime analysis and provides a solid base for the study of complex systems with intrinsic fluorescence, such as identification of the individual flavinoprotein components in living cardiac cells. This approach therefore constitutes an important instrumental advancement towards redox fluorimetry of living cardiomyocytes, with the perspective of its applications in the investigation of oxidative metabolic state under pathophysiological conditions, such as ischemia and/or metabolic disorders.