Subject-Specific Calculation of Left Atrial Appendage Blood-Borne Particle Residence Time Distribution in Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia that leads to thrombus formation, mostly in the left atrial appendage (LAA). The current standard of stratifying stroke risk, based on the CHA2DS2-VASc score, does not consider LAA morphology, and the clinically accepted LAA morphology-based classification is highly subjective. The aim of this study was to determine whether LAA blood-borne particle residence time distribution and the proposed quantitative index of LAA 3D geometry can add independent information to the CHA2DS2-VASc score. Data were collected from 16 AF subjects. Subject-specific measurements included left atrial (LA) and LAA 3D geometry obtained by cardiac computed tomography, cardiac output, and heart rate.We quantified 3D LAA appearance in terms of a novel LAA appearance complexity index (LAA-ACI). We employed computational fluid dynamics analysis and a systems-based approach to quantify residence time distribution and associated calculated variable (LAA mean residence time, tm) in each subject. The LAA-ACI captured the subject-specific LAA 3D geometry in terms of a single number. LAA tm varied significantly within a given LAA morphology as defined by the current subjectivemethod and it was not simply a reflection of LAA geometry/appearance. In addition, LAA-ACI and LAA tm varied significantly for a given CHA2DS2-VASc score, indicating that these two indices of stasis are not simply a reflection of the subjects’ clinical status. We conclude that LAA-ACI and LAA tm add independent information to the CHA2DS2-VASc score about stasis risk and thereby can potentially enhance its ability to stratify stroke risk in AF patients

PKA-Mediated Regulation of Profilin-1 - Implication in Sprouting Angiogenesis

Angiogenesis is a process of vessel outgrowth from a pre-existing capillary that is implicated in many physiological and pathological conditions. Profilin-1 (Pfn1), a ubiquitously expressed actin-binding protein, has been previously shown to be up-regulated in vascular endothelial cells during capillary morphogenesis and required for endothelial cell migration, morphogenesis and invasion in vitro. In the first part of this study, we demonstrated that depletion of Pfn1 interferes with sprouting angiogenesis in vitro and ex vivo. In the second part, we further explored how Pfn1 might be biochemically regulated. Our studies suggested that a significant fraction of Pfn1 could exist in a number of phosphorylated states in cells. We showed that Pfn1 can be phosphorylated by Protein Kinase A (PKA) in vitro and in a PKA-dependent manner in vivo. By mass-spectrometry, we identified several potential PKA phosphorylation sites of Pfn1, one of which, T89, at least also appeared to be a bona fide modification site of Pfn1 in vivo. We performed biochemical and in silico analyses to determine the potential consequence of this phosphorylation on the properties of Pfn1. Finally, we showed that activating the PKA pathway affects ligand binding of Pfn1 in cells and negatively impacts both endothelial cell migration and sprouting angiogenesis. Collectively, these observations implicate a possible role for Pfn1 post-translational modification in the PKA-mediated regulation of sprouting angiogenesis

One-Dimensional Haptic Rendering Using Audio Speaker with Displacement Determined by Inductance

We report overall design considerations and preliminary results for a new haptic rendering device based on an audio loudspeaker. Our application models tissue properties during microsurgery. For example, the device could respond to the tip of a tool by simulating a particular tissue, displaying a desired compressibility and viscosity, giving way as the tissue is disrupted, or exhibiting independent motion, such as that caused by pulsations in blood pressure. Although limited to one degree of freedom and with a relatively small range of displacement compared to other available haptic rendering devices, our design exhibits high bandwidth, low friction, low hysteresis, and low mass. These features are consistent with modeling interactions with delicate tissues during microsurgery. In addition, our haptic rendering device is designed to be simple and inexpensive to manufacture, in part through an innovative method of measuring displacement by existing variations in the speaker’s inductance as the voice coil moves over the permanent magnet. Low latency and jitter are achieved by running the real-time simulation models on a dedicated microprocessor, while maintaining bidirectional communication with a standard laptop computer for user controls and data logging

Myocardial extravascular extracellular volume fraction measurement by gadolinium cardiovascular magnetic resonance in humans: slow infusion versus bolus

<p>Abstract</p> <p>Background</p> <p>Myocardial extravascular extracellular volume fraction (Ve) measures quantify diffuse fibrosis not readily detectable by conventional late gadolinium (Gd) enhancement (LGE). Ve measurement requires steady state equilibrium between plasma and interstitial Gd contrast. While a constant infusion produces steady state, it is unclear whether a simple bolus can do the same. Given the relatively slow clearance of Gd, we hypothesized that a bolus technique accurately measures Ve, thus facilitating integration of myocardial fibrosis quantification into cardiovascular magnetic resonance (CMR) workflow routines. Assuming equivalence between techniques, we further hypothesized that Ve measures would be reproducible across scans.</p> <p>Methods</p> <p>In 10 volunteers (ages 20-81, median 33 yr, 3 females), we compared serial Ve measures from a single short axis slice from two scans: first, during a constant infusion, and second, 12-50 min after a bolus (0.2 mmol/kg gadoteridol) on another day. Steady state during infusion was defined when serial blood and myocardial T1 data varied <5%. We measured T1 on a 1.5 T Siemens scanner using a single-shot modified Look Locker inversion recovery sequence (MOLLI) with balanced SSFP. To shorten breath hold times, T1 values were measured with a shorter sampling scheme that was validated with spin echo relaxometry (TR = 15 sec) in CuSO4-Agar phantoms. Serial infusion vs. bolus Ve measures (n = 205) from the 10 subjects were compared with generalized estimating equations (GEE) with exchangeable correlation matrices. LGE images were also acquired 12-30 minutes after the bolus.</p> <p>Results</p> <p>No subject exhibited LGE near the short axis slices where Ve was measured. The Ve range was 19.3-29.2% and 18.4-29.1% by constant infusion and bolus, respectively. In GEE models, serial Ve measures by constant infusion and bolus did not differ significantly (difference = 0.1%, p = 0.38). For both techniques, Ve was strongly related to age (p < 0.01 for both) in GEE models, even after adjusting for heart rate. Both techniques identically sorted older individuals with higher mean Ve values.</p> <p>Conclusion</p> <p>Myocardial Ve can be measured reliably and accurately 12-50 minutes after a simple bolus. Ve measures are also reproducible across CMR scans. Ve estimation can be integrated into CMR workflow easily, which may simplify research applications involving the quantification of myocardial fibrosis.</p

Left Ventricular Function Depends on Previous Beat Ejection but Not Previous Beat Pressure Load

Previous beat contraction history, in which the performance of the left ventricle on any one beat is influenced by the mechanical events of the previous beat, may be important in the beat-to-beat regulation of left ventricular performance in the intact cardiovascular system. Prior studies of this phenomenon have established that mechanical events of the previous beat influence the function of the current beat, but it is not known whether the important mechanical influence is exerted by previous beat ejection or previous beat pressure. In addition, the magnitude of the effect of previous beat contraction history on left ventricular performance is unknown. To make these determinations, we performed experiments in six isolated rabbit left ventricle preparations buffer perfused at 30°C. Left ventricular pressure and volume were controlled precisely with a servo-controlled linear motor system. After steady-state ejecting conditions were established by clamping left ventricular ejection pressure at 60% of peak isovolumic pressure, single test beats, which were pressure clamped at 40%, 60%, 80%, and 100% of peak isovolumic pressure, were introduced and followed by an isovolumic reference beat. As the level of pressure clamp decreased from 100% to 40%, developed pressure on the isovolumic beat following the single test beats increased from 139±15 (mean±SD) to 151±13 mm Hg. Similarly, peak positive left ventricular dP/dt increased from 1,718±209 to 1,864±181 mm Hg · sec (both p<0.01). Multiple regression analysis showed that this increase in left ventricular function was related to previous beat ejection but not to previous beat pressure load or relaxation. These results show that previous beat contraction history, mediated by previous beat ejection, is quantitatively large enough that it could play a role in modulating the relatively small beat-to-beat adaptations that the left ventricle must continually make in the intact circulatory system. (Circulation Research 1991;69:1051–1057

Pyoderma Gangrenosum In A Child : Treated With Dexamethasone Pulse Therapy

A six year old child with recurrent and multiple lesions of pyoderma gangrenosum is reported. The disease was resistant to conventional modalities of treatment. He was treated with pulse therapy in the form of 32 mg dexamthasone in 200 ml of 5&#x0025; glucose by slow intravenous drip on two consecutive days. The pulses were repeated at two week intervals. Five such pulses led to complete and sustained healing of all the lesions

Subject-Specific Calculation of Left Atrial Appendage Blood-Borne Particle Residence Time Distribution in Atrial Fibrillation

Atrial fibrillation (AF) is the most common arrhythmia that leads to thrombus formation, mostly in the left atrial appendage (LAA). The current standard of stratifying stroke risk, based on the CHA2DS2-VASc score, does not consider LAA morphology, and the clinically accepted LAA morphology-based classification is highly subjective. The aim of this study was to determine whether LAA blood-borne particle residence time distribution and the proposed quantitative index of LAA 3D geometry can add independent information to the CHA2DS2-VASc score. Data were collected from 16 AF subjects. Subject-specific measurements included left atrial (LA) and LAA 3D geometry obtained by cardiac computed tomography, cardiac output, and heart rate.We quantified 3D LAA appearance in terms of a novel LAA appearance complexity index (LAA-ACI). We employed computational fluid dynamics analysis and a systems-based approach to quantify residence time distribution and associated calculated variable (LAA mean residence time, tm) in each subject. The LAA-ACI captured the subject-specific LAA 3D geometry in terms of a single number. LAA tm varied significantly within a given LAA morphology as defined by the current subjectivemethod and it was not simply a reflection of LAA geometry/appearance. In addition, LAA-ACI and LAA tm varied significantly for a given CHA2DS2-VASc score, indicating that these two indices of stasis are not simply a reflection of the subjects’ clinical status. We conclude that LAA-ACI and LAA tm add independent information to the CHA2DS2-VASc score about stasis risk and thereby can potentially enhance its ability to stratify stroke risk in AF patients