Acellular Myocardial Scaffolds and Slices Fabrication, and Method for Applying Mechanical and Electrical Simulation to Tissue Construct.

Cardiac tissue engineering/regeneration using decellularized myocardium has attracted great research attention due to its potential benefit to myocardial infarction (MI) treatment. Here, we described an optimal decellularization protocol to generate 3D porcine myocardial scaffolds with well-preserved cardiomyocyte lacunae, myocardial slices as a biomimetic cell culture and delivery platform, and a multi-stimulation bioreactor that is able to provide coordinated mechanical and electrical stimulations for facilitating cardiac construct development.

Focality of the Induced E-Field Is a Contributing Factor in the Choice of TMS Parameters: Evidence from a 3D Computational Model of the Human Brain.

Transcranial magnetic stimulation (TMS) is a promising, non-invasive approach in the diagnosis and treatment of several neurological conditions. However, the specific results in the cortex of the magnitude and spatial distribution of the secondary electrical field (E-field) resulting from TMS at different stimulation sites/orientations and varied TMS parameters are not clearly understood. The objective of this study is to identify the impact of TMS stimulation site and coil orientation on the induced E-field, including spatial distribution and the volume of activation in the cortex across brain areas, and hence demonstrate the need for customized optimization, using a three-dimensional finite element model (FEM).

Telemetry-controlled simultaneous stimulation-and-recording device (SRD) to study interhemispheric cortical circuits in rat primary somatosensory (SI) cortex.

Background: A growing need exists for neuroscience platforms that can perform simultaneous chronic recording and stimulation of neural tissue in animal models in a telemetry-controlled fashion with signal processing for analysis of the chronic recording data and external triggering capability. We describe the system design, testing, evaluation, and implementation of a wireless simultaneous stimulation-and-recording device (SRD) for modulating cortical circuits in physiologically identified sites in primary somatosensory (SI) cortex in awake-behaving and freely-moving rats. The SRD was developed using low-cost electronic components and open-source software.

Seizure Prediction and Detection via Phase and Amplitude Lock Values.

A robust seizure prediction methodology would enable a "closed-loop" system that would only activate as impending seizure activity is detected. Such a system would eliminate ongoing stimulation to the brain, thereby eliminating such side effects as coughing, hoarseness, voice alteration, and paresthesias (Murphy et al., 1998; Ben-Menachem, 2001), while preserving overall battery life of the system.

Esophageal electric fields are predictive of atrial cardioversion success-a finite element analysis.

Background: Atrial fibrillation (AF) is a debilitating cardiac arrhythmia, one potential treatment of which is external cardioversion. Studies have shown external cardioversion success is affected by electrode placement and that esophageal electric fields (EEFs) during low strength shocks have the potential to be used in determining patient-specific optimal electrode placements during animal experiments. The objective of this study was to determine the relationship between EEFs and atrial defibrillation thresholds (ADFTs) during computer simulations using an anatomically realistic computer model of a human torso.

Differential Pattern of Interhemispheric Connections Between Homotopic Layer V Regions in the Forelimb Representation in Rat Barrel Field Cortex.

Layer V neurons in forelimb and shoulder representations in rat first somatosensory cortex (SI) project to the contralateral SI. However, few studies have addressed whether projections from specific subregions of the forelimb representation, namely forepaw, wrist, or forearm, terminate at homotopic sites in the contralateral SI. Neuroanatomical retrograde (cholera toxin B subunit [CT-B]) or anterograde (biodextran amine [BDA]) tracers were injected into physiologically identified sites in layer V in specific forelimb and/or shoulder representations in SI to examine the projection to contralateral SI in young adult rats (N = 17).

Effects of macroscopic heterogeneity on propagation in a computationally inexpensive 2D model of the heart.

We have developed a computationally inexpensive, two-dimensional, bidomain model of the heart to demonstrate the effect of tissue heterogeneity on propagation of cardiac impulses generated by the sino-atrial node (SAN). The geometry consists of a thin sheet of cardiac tissue with designated areas that represent the SAN and atria. The SAN auto-generates continuous impulses that result in waves of normal propagation throughout the tissue.

Wireless simultaneous stimulation-and-recording device to train cortical circuits in somatosensory cortex.

We describe for the first time the design, implementation, and testing of a telemetry controlled simultaneous stimulation and recording device (SRD) to deliver chronic intercortical microstimulation (ICMS) to physiologically identified sites in rat somatosensory cortex (SI) and test hypotheses that chronic ICMS strengthens interhemispheric pathways and leads to functional reorganization in the enhanced cortex. The SRD is a custom embedded device that uses the Cypress Semiconductor's programmable system on a chip (PSoC) that is remotely controlled via Bluetooth. The SRC can record single or multiunit responses from any two of 12 available inputs at 1-15 ksps per channel and simultaneously deliver stimulus pulses (0-255 μA; 10 V compliance) to two user selectable electrodes using monophasic, biphasic, or pseudophasic stimulation waveforms (duration: 0-5 ms, inter-phase interval: 0-5 ms, frequency: 0.

Myocardial scaffold-based cardiac tissue engineering: application of coordinated mechanical and electrical stimulations.

Recently, we developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserve the natural extracellular matrix structure, mechanical anisotropy, and vasculature templates and also show good cell recellularization and differentiation potential. In this study, a multistimulation bioreactor was built to provide coordinated mechanical and electrical stimulation for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (10(6) cells/mL) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols.

Structural and biomechanical characterizations of porcine myocardial extracellular matrix.

Extracellular matrix (ECM) of myocardium plays an important role to maintain a multilayered helical architecture of cardiomyocytes. In this study, we have characterized the structural and biomechanical properties of porcine myocardial ECM. Fresh myocardium were decellularized in a rotating bioreactor using 0.

An esophageal probe for measuring three-dimensional electric fields during external cardiac defibrillation.

External defibrillation is a common treatment for the cardiac arrhythmia atrial fibrillation. Electrode placement has been shown to affect defibrillation efficacy and required energy levels. We suggest investigating the relationship between esophageal electric fields (EEFs) and atrial defibrillation thresholds to determine the feasibility of creating patient-specific electrode placements using EEFs.

Esophageal electric fields are predictive of atrial defibrillation thresholds.

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia characterized by disorganized cardiac electrical activity. Defibrillation electrode placement has been shown to affect the amount of energy and number of shocks required to defibrillate. The objective of this study was to investigate the relationship between esophageal electric fields (EEFs) and atrial defibrillation thresholds (ADFTs) to determine the feasibility of using EEFs during a low-strength shock to predict patient-specific defibrillation electrode placements.

Spironolactone prevents the inducibility of ventricular tachyarrhythmia in rats with aldosteronism.

Myocardial fibrosis is considered a substrate for fatal ventricular arrhythmias (VAs). In rats receiving aldosterone/salt treatment (ALDOST) for ≥4 weeks, foci of myocardial scarring that replace necrotic cardiomyocytes appear scattered throughout the right and left sides of the heart. We hypothesized that this adverse structural remodeling would promote the inducibility of VA, which could be prevented by cotreatment with spironolactone (A+Spiro), an aldosterone receptor antagonist and cardioprotective agent.

Fabrication of cardiac patch with decellularized porcine myocardial scaffold and bone marrow mononuclear cells.

Tissue engineered cardiac grafts are a promising therapeutic mode for ventricular wall reconstruction. Recently, it has been found that acellular tissue scaffolds provide natural ultrastructural, mechanical, and compositional cues for recellularization and tissue remodeling. We thus assess the potential of decellularized porcine myocardium as a scaffold for thick cardiac patch tissue engineering.

Transthoracic atrial defibrillation energy thresholds are correlated to uniformity of current density distributions.

Previous studies have shown that successful defibrillation depends on the uniformity of current density in the heart and the percentage of total current reaching the heart. This study uses an anatomically-realistic finite element computer model of the human torso for external atrial defibrillation to (1) examine the defibrillation energy thresholds and current density distributions for common clinical paddle placements and (2) investigate the effects of electrode shifts on these defibrillation parameters. The model predicts atrial defibrillation threshold (AD FT) energy by requiring a voltage gradient of 5 V/cm over at least 95% of atrial myocardium.