Mangumyates1403

There is increasing evidence on the role of the autonomic nervous system in the pathogenesis of atrial fibrillation. Interventions targeting autonomic modulation of atrial electrical activity have been shown to reduce the incidence of atrial arrhythmias. Additionally, recent investigations have proved that pharmacological therapies inhibiting small-conductance calcium-activated potassium (SK) channels are able to lessen cholinergic effects in the atria.In this study we use computational modeling and simulation to test individual and combined effects of SK channel block and adrenergic stimulation in counteracting detrimental effects induced by the parasympathetic neurotransmitter acetylcholine (ACh) on human atrial electrophysiology. Cell and tissue models are built that incorporate descriptions of SK channels as well as of isoproterenol (Iso)- and ACh-mediated regulation of the atrial action potential (AP). Three different cellular AP models, representing a range of physiological AP shapes, are considered and both homogeneous and heterogeneous ACh distributions in atrial tissue are simulated.At the cellular level, SK channel block is demonstrated to partially revert shortening of AP duration (APD) mediated by ACh at various doses, whereas 1 µM Iso has a variable response depending on the AP shape. The combination of SK block and Iso is in all cases able to take APD back to baseline levels, recovering between 82% and 120% of the APD shortening induced by 0.1 µM ACh. At the tissue level, SK block and Iso alone or in combination do not exert remarkable effects on conduction velocity, but the combination of the two is able to notably prolong the ACh-mediated APD shortening, thus increasing the wavelength for reentry.In conclusion, the results from this study support the combination of SK channel block and adrenergic stimulation as a potential option to counteract parasympathetically-mediated proarrhythmic effects in the human atria.The fluid dynamics of microporous materials are important to many biomedical processes such as cell deposition in scaffold materials, tissue engineering, and bioreactors. Microporous scaffolds are frequently composed of suspensions of beads that have varying topology which, in turn, informs their hydrodynamic properties. Previous work has shown that shear stress distributions can affect the response of cells in microporous environments. Using computational fluid dynamics, we characterize localized differences in fluid flow attributes such wall shear stress and velocity to better understand the fluid dynamics underpinning microporous device function. We evaluated whether bead packings with similar void fractions had different fluid dynamics as characterized by the distribution of velocity magnitudes and wall shear stress and found that there are differences despite the similarities in void fraction. We show that another metric, the average distance to the nearest wall, can provide an additional variable to measure the porosity and susceptibility of microporous materials to high shear stress. By increasing our understanding of the impact of bead size on cell scaffold fluid dynamics we aim to increase the ability to predict important attributes such as loading efficiency in these devices.This paper proposes a novel method to noninvasively measure the peak systolic pressure difference (PSPD) across coarctation of the aorta for diagnosing the severity of coarctation. Traditional non-invasive estimates of pressure drop from the ultrasound can underestimate the severity and invasive measurements by cardiac catheterization can carry risks for patients. Ceftaroline To address the issues, we employ computational fluid dynamics (CFD) computation to accurately predict the PSPD across a coarctation based on cardiac magnetic resonance (CMR) imaging data and cuff pressure measurements from one arm. The boundary conditions of a patient-specific aorta model are specified at the inlet of the ascending aorta by using the time-dependent blood velocity, and the outlets of descending aorta and supra aortic branches by using a 3-element Windkessel model. To estimate the parameters of the Windkessel model, steady flow simulations were performed using the time-averaged flow rates in the ascending aorta, descending aorta, and two of the three supra aortic branches. The mean cuff pressure from one arm was specified at the outlet of one of the supra aortic branches. The CFD predicted PSPDs of 5 patients (n=5) were compared with the invasively measured pressure drops obtained by catheterization. The PSPDs were accurately predicted (mean µ=0.3mmHg, standard deviation σ =4.3mmHg) in coarctation of the aorta using completely non-invasive flow and cuff pressure data. The results of our study indicate that the proposed method could potentially replace invasive measurements for estimating the severity of coarctations.Clinical relevance-Peak systolic pressure drop is an indicator of the severity of coarctation of the aorta. It can be predicted without any additional risks to patients using non-invasive cuff pressure and flow data from CMR.The computational model plays a vital role in the design and optimization of microelectrodes for efficient electrical stimulation and recording in the retinal prosthesis. Moreover, the material choice acts decisively in ensuring that the electronic device delivers sufficient stimulating current to the retina without harming the neighboring tissue. Recently, due to the enhanced electrical and electrochemical properties of graphene, it has become a viable material in biomedical applications. In this study, we analyzed the computational model for the retinal prosthesis by the novel use of graphene-based microelectrodes. For this, different topologies of the electrode arrangement were investigated. The most suitable configuration involves the arrangement of electrodes serving as the ground in a hexagonal fashion around the central stimulating electrode. We observed that the performance of graphene as the stimulating electrodes is comparable to the existing noble metal-based electrodes. Moreover, we found that optimizing the microelectrode design resulted in uniform electric potential distribution, and this eventually led to an increased electric field intensity at the desired activation point. Additionally, we analyzed the crosstalk phenomenon, and we observed from the results that it is better to implant such an electrode array in the vicinity of the targeted volume to minimize the effect of crosstalk.Clinical relevance- The present study can help in the improvement of the retinal prosthesis by analyzing the quantitative and qualitative effects of graphene-based microelectrodes on producing the threshold electric field in the retina tissue. The results obtained can be used to optimize the implantable microelectrode design and thus is a step forward in finding a cure to vision impairment diseases.