Detection of abnormal myocardial deformation during acute myocardial ischemia using three-dimensional speckle tracking echocardiography

Background: Three-dimensional (3D) speckle tracking echocardiography can simultaneously evaluate circumferential, longitudinal, and radial strain without being affected by through-plane motion. Moreover, the assessment of area change ratio may allow measuring regional myocardial deformation more accurately. We investigated the changes in each deformation parameter during acute coronary flow reduction, and evaluated whether the spatial extent of the abnormal values in each deformation parameter corresponded to that of the perfusion abnormality. Methods: In 10 dogs, myocardial strains of three directions and area change ratio were analyzed at baseline and during three different ischemic conditions. The peak systolic value and the post-systolic index (PSI) were measured in both the ischemic and normal segments. The function abnormality, derived from the deformation parameter, and the perfusion abnormality, derived from Evans blue staining, were evaluated in each segment during complete occlusion and the concordance rate between both abnormalities was calculated. Results: In all deformation parameters, the peak systolic value tended to gradually decrease and the PSI tended to gradually increase with the severity of flow reduction in the ischemic segment. Especially in area change ratio, significant changes were observed in both the peak systolic value and the PSI during occlusion compared to baseline. The concordance rate was the highest in the PSI assessed by area change ratio. Conclusions: Among 3D myocardial deformation parameters, area change ratio demonstrated better detectability of acute coronary flow reduction than conventional strain components. Area change ratio may be a useful parameter for detecting acute ischemia by 3D speckle tracking echocardiography.This is a post-peer-review, pre-copyedit version of an article published in Journal of Echocardiography. The final authenticated version is available online at: http://dx.doi.org/10.1007/s12574-019-00449-6.https://doi.org/10.1007/s12574-019-00449-

Myocardial layer-specific analysis of ischemic memory using speckle tracking echocardiography

The assessment of post-systolic shortening (PSS) by speckle tracking echocardiography allows myocardial ischemic memory imaging. Because the endocardial layer is more vulnerable to ischemia, the assessment of this layer might be useful for detecting ischemic memory. Serial echocardiographic data were acquired from nine dogs with 2 min of coronary occlusion followed by reperfusion. Regional deformation parameters were measured in the risk and normal areas. Using speckle tracking echocardiography, circumferential strain was analyzed in the endocardial, mid-wall, and epicardial layers; and radial strain was analyzed in the inner half, outer half and entire (transmural) layers. In the risk area, peak systolic and end-systolic strain in the circumferential and radial directions significantly decreased during occlusion, but recovered to the baseline levels immediately after reperfusion in all layers. However, circumferential post-systolic strain index (PSI), a parameter of PSS, significantly increased during occlusion, and the significant increases persisted until 20 min after reperfusion in the endocardial and mid-wall layers. Radial PSI tended to increase after reperfusion in the inner half and entire layers but these increases were not significant compared with baseline. In the normal area, systolic strains and PSI in the radial and circumferential directions hardly changed before and after occlusion/reperfusion in all layers. In layer-specific analysis with speckle tracking echocardiography, circumferential PSS in the endocardial and mid-wall layers may be useful for detecting ischemic memory. © 2014 Springer Science+Business Media.This is a post-peer-review, pre-copyedit version of an article published in International Journal of Cardiovascular Imaging. The final authenticated version is available online at: https://doi.org/10.1007/s10554-014-0388-x

Upregulation of casein kinase 1ε in dorsal root ganglia and spinal cord after mouse spinal nerve injury contributes to neuropathic pain

<p>Abstract</p> <p>Background</p> <p>Neuropathic pain is a complex chronic pain generated by damage to, or pathological changes in the somatosensory nervous system. Characteristic features of neuropathic pain are allodynia, hyperalgesia and spontaneous pain. Such abnormalities associated with neuropathic pain state remain to be a significant clinical problem. However, the neuronal mechanisms underlying the pathogenesis of neuropathic pain are complex and still poorly understood. Casein kinase 1 is a serine/threonine protein kinase and has been implicated in a wide range of signaling activities such as cell differentiation, proliferation, apoptosis, circadian rhythms and membrane transport. In mammals, the CK1 family consists of seven members (α, β, γ1, γ2, γ3, δ, and ε) with a highly conserved kinase domain and divergent amino- and carboxy-termini.</p> <p>Results</p> <p>Preliminary cDNA microarray analysis revealed that the expression of the <it>casein kinase 1 epsilon </it>(<it>CK1ε</it>) mRNA in the spinal cord of the neuropathic pain-resistant N- type Ca²⁺channel deficient (<it>Ca</it>_<it>v</it><it>2.2</it>^-/-) mice was decreased by the spinal nerve injury. The same injury exerted no effects on the expression of <it>CK1ε </it>mRNA in the wild-type mice. Western blot analysis of the spinal cord identified the downregulation of CK1ε protein in the injured <it>Ca</it>_<it>v</it><it>2.2</it>^-/-mice, which is consistent with the data of microarray analysis. However, the expression of CK1ε protein was found to be up-regulated in the spinal cord of injured wild-type mice. Immunocytochemical analysis revealed that the spinal nerve injury changed the expression profiles of CK1ε protein in the dorsal root ganglion (DRG) and the spinal cord neurons. Both the percentage of CK1ε-positive neurons and the expression level of CK1ε protein were increased in DRG and the spinal cord of the neuropathic mice. These changes were reversed in the spinal cord of the injured <it>Ca</it>_<it>v</it><it>2.2</it>^-/-mice. Furthermore, intrathecal administration of a CK1 inhibitor IC261 produced marked anti-allodynic and anti-hyperalgesic effects on the neuropathic mice. In addition, primary afferent fiber-evoked spinal excitatory responses in the neuropathic mice were reduced by IC261.</p> <p>Conclusions</p> <p>These results suggest that CK1ε plays important physiological roles in neuropathic pain signaling. Therefore CK1ε is a useful target for analgesic drug development.</p

A history of mild shocks experienced by the regolith particles on hydrated asteroid Ryugu

Micrometeorites, a possible major source of Earth’s water, are thought to form from explosive dispersal of hydrated chondritic materials during impact events on their parental asteroids. However, this provenance and formation mechanism have yet to be directly confirmed using asteroid returned samples. Here, we report evidence of mild shock metamorphism in the surface particles of asteroid Ryugu based on electron microscopy. All particles are dominated by phyllosilicates but lack dehydration textures, which are indicative of shock-heating temperatures below ~500 °C. Microfault-like textures associated with extensively shock-deformed framboidal magnetites and a high-pressure polymorph of Fe–Cr–sulfide have been identified. These findings indicate that the average peak pressure was -2 GPa. The vast majority of ejecta formed during impact on Ryugu-like asteroids would be hydrated materials, larger than a millimetre, originating far from the impact point. These characteristics are inconsistent with current micrometeorite production models, and consequently, a new formation mechanism is required

Oxygen isotope evidence from Ryugu samples for early water delivery to Earth by CI chondrites

The delivery of water to the inner Solar System, including Earth, is still a debated topic. A preferential role for hydrated asteroids in this process is supported by isotopic measurements. Carbonaceous chondrite (CC) meteorites represent our main source of information about these volatile-rich asteroids. However, the destruction of weaker materials during atmospheric entry creates a bias in our CC data. The return of surface materials from the C-type asteroid 162173 Ryugu by the Hayabusa2 spacecraft provides a unique opportunity to study high-porosity, low-density, primitive materials, unrepresented in the meteorite record. We measured the bulk oxygen isotope composition from four Ryugu particles and show that they most closely resemble the rare CI (CC Ivuna-type) chondrites, but with some differences that we attribute to the terrestrial contamination of the CI meteorites. We suggest that CI-related material is widespread among carbonaceous asteroids and a more important source of Earth’s water and other volatiles than its limited presence in our meteoritic collection indicates

A pristine record of outer Solar System materials from asteroid Ryugu’s returned sample

Volatile and organic-rich C-type asteroids may have been one of the main sources of Earth’s water. Our best insight into their chemistry is currently provided by carbonaceous chondritic meteorites, but the meteorite record is biased: only the strongest types survive atmospheric entry and are then modified by interaction with the terrestrial environment. Here we present the results of a detailed bulk and microanalytical study of pristine Ryugu particles, brought to Earth by the Hayabusa2 spacecraft. Ryugu particles display a close compositional match with the chemically unfractionated, but aqueously altered, CI (Ivuna-type) chondrites, which are widely used as a proxy for the bulk Solar System composition. The sample shows an intricate spatial relationship between aliphatic-rich organics and phyllosilicates and indicates maximum temperatures of ~30 °C during aqueous alteration. We find that heavy hydrogen and nitrogen abundances are consistent with an outer Solar System origin. Ryugu particles are the most uncontaminated and unfractionated extraterrestrial materials studied so far, and provide the best available match to the bulk Solar System composition