The role of conductivity discontinuities in design of cardiac defibrillation.

Fibrillation is an erratic electrical state of the heart, of rapid twitching rather than organized contractions. Ventricular fibrillation is fatal if not treated promptly. The standard treatment, defibrillation, is a strong electrical shock to reinitialize the electrical dynamics and allow a normal heart beat. Both the normal and the fibrillatory electrical dynamics of the heart are organized into moving wave fronts of changing electrical signals, especially in the transmembrane voltage, which is the potential difference between the cardiac cellular interior and the intracellular region of the heart. In a normal heart beat, the wave front motion is from bottom to top and is accompanied by the release of Ca ions to induce contractions and pump the blood. In a fibrillatory state, these wave fronts are organized into rotating scroll waves, with a centerline known as a filament. Treatment requires altering the electrical state of the heart through an externally applied electrical shock, in a manner that precludes the existence of the filaments and scroll waves. Detailed mechanisms for the success of this treatment are partially understood, and involve local shock-induced changes in the transmembrane potential, known as virtual electrode alterations. These transmembrane alterations are located at boundaries of the cardiac tissue, including blood vessels and the heart chamber wall, where discontinuities in electrical conductivity occur. The primary focus of this paper is the defibrillation shock and the subsequent electrical phenomena it induces. Six partially overlapping causal factors for defibrillation success are identified from the literature. We present evidence in favor of five of these and against one of them. A major conclusion is that a dynamically growing wave front starting at the heart surface appears to play a primary role during defibrillation by critically reducing the volume available to sustain the dynamic motion of scroll waves; in contrast, virtual electrodes occurring at the boundaries of small, isolated blood vessels only cause minor effects. As a consequence, we suggest that the size of the heart (specifically, the surface to volume ratio) is an important defibrillation variable.

Euler equation existence, non-uniqueness and mesh converged statistics.

We review existence and non-uniqueness results for the Euler equation of fluid flow. These results are placed in the context of physical models and their solutions. Non-uniqueness is in direct conflict with the purpose of practical simulations, so that a mitigating strategy, outlined here, is important. We illustrate these issues in an examination of mesh converged turbulent statistics, with comparison to laboratory experiments.

Nonideal Rayleigh-Taylor mixing.

Rayleigh-Taylor mixing is a classical hydrodynamic instability that occurs when a light fluid pushes against a heavy fluid. The two main sources of nonideal behavior in Rayleigh-Taylor (RT) mixing are regularizations (physical and numerical), which produce deviations from a pure Euler equation, scale invariant formulation, and nonideal (i.e., experimental) initial conditions. The Kolmogorov theory of turbulence predicts stirring at all length scales for the Euler fluid equations without regularization. We interpret mathematical theories of existence and nonuniqueness in this context, and we provide numerical evidence for dependence of the RT mixing rate on nonideal regularizations; in other words, indeterminacy when modeled by Euler equations. Operationally, indeterminacy shows up as nonunique solutions for RT mixing, parametrized by Schmidt and Prandtl numbers, in the large Reynolds number (Euler equation) limit. Verification and validation evidence is presented for the large eddy simulation algorithm used here. Mesh convergence depends on breaking the nonuniqueness with explicit use of the laminar Schmidt and Prandtl numbers and their turbulent counterparts, defined in terms of subgrid scale models. The dependence of the mixing rate on the Schmidt and Prandtl numbers and other physical parameters will be illustrated. We demonstrate numerically the influence of initial conditions on the mixing rate. Both the dominant short wavelength initial conditions and long wavelength perturbations are observed to play a role. By examination of two classes of experiments, we observe the absence of a single universal explanation, with long and short wavelength initial conditions, and the various physical and numerical regularizations contributing in different proportions in these two different contexts.

The influence of contralateral circulation on computational fluid dynamics of intracranial arteries: simulated versus measured flow velocities.

BACKGROUND: This study aimed to retrospectively evaluate the influence of contralateral anterior circulation on computational fluid dynamics (CFD) of intracranial arteries, by comparing the CFD values of flow velocities in unilateral anterior circulation with the measured values from phase-contrast magnetic resonance angiography (PC-MRA). METHODS: We analyzed 21 unilateral anterior circulation models without proximal stenosis from 15 patients who performed both time-of-flight MRA (TOF-MRA) and PC-MRA. CFD was performed with the inflow boundary condition of a pulsatile flow of the internal carotid artery (ICA) obtained from PC-MRA. The outflow boundary condition was given as atmospheric pressure. Simulated flow velocities of the middle cerebral artery (MCA) and anterior cerebral artery (ACA) from CFD were compared with the measured values from PC-MRA. RESULTS: The velocities of MCA were shown to be more accurately simulated on CFD than those of ACA (Spearman correlation coefficient 0.773 and 0.282, respectively). In four models with severe stenosis or occlusion of the contralateral ICA, the CFD values of ACA velocities were significantly lower (< 50%) than those measured with PC-MRA. ACA velocities were relatively accurately simulated in the models including similar diameters of both ACAs. CONCLUSION: It may be necessary to consider the flow condition of the contralateral anterior circulation in CFD of intracranial arteries, especially in the ACA. RELEVANCE STATEMENT: Incorporating the flow conditions of the contralateral circulation is of clinical importance for an accurate prediction of a rupture risk in Acom aneurysms as the bidirectional flow and accurate velocity of both ACAs can significantly impact the CFD results. KEY POINTS: • CFD simulations using unilateral vascular models were relatively accurate for MCA. • Contralateral ICA steno-occlusion resulted in an underestimation of CFD velocity in ACA. • Contralateral flow may need to be considered in CFD simulations of ACA.

Interactive 3D Human Heart Simulations on Segmented Human MRI Hearts.

Understanding cardiac arrhythmic mechanisms and developing new strategies to control and terminate them using computer simulations requires realistic physiological cell models with anatomically accurate heart structures. Furthermore, numerical simulations must be fast enough to study and validate model and structure parameters. Here, we present an interactive parallel approach for solving detailed cell dynamics in high-resolution human heart structures with a local PC's GPU. In vitro human heart MRI scans were manually segmented to produce 3D structures with anatomically realistic electrophysiology. The Abubu.js library was used to create an interactive code to solve the OVVR human ventricular cell model and the FDA extension of the model in the human MRI heart structures, allowing the simulation of reentrant waves and investigation of their dynamics in real time. Interactive simulations of a physiological cell model in a detailed anatomical human heart reveals propagation of waves through the fine structures of the trabeculae and pectinate muscle that can perpetuate arrhythmias, thereby giving new insights into effects that may need to be considered when planning ablation and other defibrillation methods.

Angiographic pattern of symptomatic severe M1 stenosis: comparison with presenting symptoms, infarct patterns, perfusion status, and outcome after recanalization.

BACKGROUND: Several angiographic patterns distal to severe M1 stenosis have been identified. We have assessed the relationship between these angiographic patterns and patient presenting symptoms, infarct patterns, perfusion status and outcome after recanalization. METHODS: Three angiographic patterns were retrospectively identified in 60 patients (M:F = 41:19; age range = 34-80 years, mean = 55) who underwent M1 stenting: (1) a normal pattern (n = 22); (2) a shift pattern of the borderzone of the anterior cerebral artery (ACA) and middle cerebral artery (MCA) down to the MCA side with decreased size of MCA branches (n = 16), and (3) a dilatation pattern of the MCA branches with slow flow and minimal shift of borderzone (n = 22). In addition, to analyze interreader agreement, we assessed the correlation between angiographic patterns and gender, presenting symptoms (stroke vs. TIA), infarct patterns on MRI (borderzone vs. non-borderzone infarcts), perfusion results and outcome after stenting by chi(2) or Fisher's exact test. RESULTS: Blind review revealed an excellent interreader agreement in the assessment of angiographic patterns (kappa = 0.681). The shift pattern was more common in women than in men (p = 0.007). The likelihood of stroke (25/60, 42%, p = 0.001), borderzone infarct (21/32, 66%, p = 0.010) and decreased perfusion (p < 0.001) were greatest in the dilatation pattern, followed by shift and normal patterns. The outcomes did not differ by angiographic pattern probably due to the low event rate (4/60, 6.7%) within 6 months. CONCLUSIONS: Patients with severe M1 stenosis had 3 different angiographic patterns, which correlated with presenting symptoms, infarct patterns and perfusion status. Differences in patterns may be related to variation in collateral circulation at the ACA-MCA borderzone and hypoperfusion status.

Chrysin Increases the Therapeutic Efficacy of Docetaxel and Mitigates Docetaxel-Induced Edema.

Docetaxel (DTX) is an effective commercial anticancer agent for chemotherapy in non-small cell lung cancer (NSCLC), breast cancer, gastric cancer, and prostate cancer, but its adverse effects including edema, neurotoxicity, and hair loss limit its application. To improve the chemotherapeutic efficacy of DTX and reduce adverse effects, combination therapy is one of the alternative methods. So chrysin, which has various biological activities including anticancer effects, was considered. In vitro, the combination of chrysin and DTX was investigated in A549 cells. Increased cytotoxicity, suppressed cellular proliferation, and induced apoptosis were observed with posttreatment of chrysin following DTX treatment. In vivo, chrysin enhanced the tumor growth delay of DTX and increased DTX-induced apoptosis in the A549-derived xenograft model. Furthermore, chrysin prevented DTX-induced edema in ICR mouse. These results indicated that chrysin strengthened the therapeutic efficacy of DTX and diminished the adverse effect of DTX, suggesting chrysin could be exploited as an adjuvant therapy for NSCLC.

Evaluation for fracture patterns around the wrist on three-dimensional extremity computed tomography, especially focused on the triquetrum.

INTRODUCTION: To describe fracture patterns of triquetrum and analyse them according to fracture classifications, anatomy of intrinsic carpal ligaments and comparison with other wrist fractures. METHODS: We retrospectively reviewed 297 three-dimensional extremity computed tomographies (CTs) on wrist fractures from October 2007 to January 2012. We initially classified the fractures according to the involved bones and analyzed them according to the patterns of triquetrum fractures, associated carpal bone fractures and presence of combined distal radius fractures. We also correlated the fracture patterns with the patient's injury patterns. RESULTS: A total of 297 CTs and 291 patients were included (162 males and 129 females; mean age, 47.8 years). There were a total of 131 carpal bone fractures in 102 patients of 102 CTs. Triquetrum fractures were the most commonly observed cases (36 cases/27.5%). For the triquetrum fractures, the following types were observed: 26 dorsal, five volar, two comminuted fractures are observed in triquetrum. Three other triquetrum fractures show combined forms of other carpal bone fractures. For the combined distal radius fractures, 10 dorsal and two volar fractures were shown. Out of 187 distal radius fractures, 20 showed carpal bone fractures (10.7%). There were no differences in injury patterns according to the fracture patterns. The most common pattern of injury was falling on the outstretched hand, followed by fall from height. CONCLUSION: The dorsum of triquetrum is more frequently fractured than the volar aspect. The number of carpal bone fractures among the patients who have distal radius fractures is higher than usual expectation.

New directions for Rayleigh-Taylor mixing.

We study the Rayleigh-Taylor (RT) mixing layer, presenting simulations in agreement with experimental data. This problem is an idealized subproblem of important scientific and engineering problems, such as gravitationally induced mixing in oceanography and performance assessment for inertial confinement fusion. Engineering codes commonly achieve correct simulations through the calibration of adjustable parameters. In this sense, they are interpolative and not predictive. As computational science moves from the interpolative to the predictive and reduces the reliance on experiment, the quality of decision making improves. The diagnosis of errors in a multi-parameter, multi-physics setting is daunting, so we address this issue in the proposed idealized setting. The validation tests presented are thus a test for engineering codes, when used for complex problems containing RT features. The RT growth rate, characterized by a dimensionless but non-universal parameter α, describes the outer edge of the mixing zone. Increasingly accurate front tracking/large eddy simulations reveal the non-universality of the growth rate and agreement with experimental data. Increased mesh resolution allows reduction in the role of key subgrid models. We study the effect of long-wavelength perturbations on the mixing growth rate. A self-similar power law for the initial perturbation amplitudes is here inferred from experimental data. We show a maximum ±5% effect on the growth rate. Large (factors of 2) effects, as predicted in some models and many simulations, are inconsistent with the experimental data of Youngs and co-authors. The inconsistency of the model lies in the treatment of the dynamics of bubbles, which are the shortest-wavelength modes for this problem. An alternative theory for this shortest wavelength, based on the bubble merger model, was previously shown to be consistent with experimental data.