Skin sympathetic nerve activity precedes the onset and termination of paroxysmal atrial tachycardia and fibrillation

Background Skin sympathetic nerve activity (SKNA) is useful for estimating sympathetic tone in humans. Objective The purpose of this study was to test the hypotheses that (1) increased SKNA is associated with the onset and termination of paroxysmal atrial tachycardia (AT) and atrial fibrillation (AF) and (2) sinoatrial node response to SKNA is reduced in patients with more frequent AT or AF episodes. Methods SKNA and electrocardiogram were recorded in 11 patients (4 men and 7 women; average age 66 ± 10 years), including 3 patients with AT (11 ± 18 episodes per patient) and 8 patients with AF (24 ± 26 episodes per patient). Results The average SKNA (aSKNA) 10 seconds before AT onset was 1.07 ± 0.10 μV and 10 seconds after termination was 1.27 ± 0.10 μV; both were significantly (P = .032 and P < .0001) higher than that during sinus rhythm (0.97 ± 0.09 μV). The aSKNA 10 seconds before AF onset was 1.34 ± 0.07 μV and 10 seconds after termination was 1.31 ± 0.07 μV; both were significantly (P < .0001) higher than that during sinus rhythm (1.04 ± 0.07 μV). The aSKNA before onset (P < .0001) and after termination (P = .0011) was higher in AF than in AT. The sinus rate correlated (P < .0001) with aSKNA in each patient (average r = 0.74; 95% confidence interval 0.65–0.84). The r value in each patient negatively correlated with the number of AT and AF episodes (r = −0.6493; 95% confidence interval −0.8990 to −0.08073; P = .0306). Conclusion Increased SKNA was observed both at the onset and termination of AT and AF. Patients with more frequent AT and AF episodes had a weak correlation between sinus rate and aSKNA, suggesting sinoatrial node remodeling by tachycardia

Concomitant SK current activation and sodium current inhibition cause J wave syndrome

The mechanisms of J wave syndrome (JWS) are incompletely understood. Here, we showed that the concomitant activation of small-conductance calcium-activated potassium (SK) current (IKAS) and inhibition of sodium current by cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) recapitulate the phenotypes of JWS in Langendorff-perfused rabbit hearts. CyPPA induced significant J wave elevation and frequent spontaneous ventricular fibrillation (SVF), as well as sinus bradycardia, atrioventricular block, and intraventricular conduction delay. IKAS activation by CyPPA resulted in heterogeneous shortening of action potential (AP) duration (APD) and repolarization alternans. CyPPA inhibited cardiac sodium current (INa) and decelerated AP upstroke and intracellular calcium transient. SVFs were typically triggered by short-coupled premature ventricular contractions, initiated with phase 2 reentry and originated more frequently from the right than the left ventricles. Subsequent IKAS blockade by apamin reduced J wave elevation and eliminated SVF. β-Adrenergic stimulation was antiarrhythmic in CyPPA-induced electrical storm. Like CyPPA, hypothermia (32.0°C) also induced J wave elevation and SVF. It facilitated negative calcium-voltage coupling and phase 2 repolarization alternans with spatial and electromechanical discordance, which were ameliorated by apamin. These findings suggest that IKAS activation contributes to the development of JWS in rabbit ventricles

A heterozygous mutation in NOTCH3 in a Chinese family with CADASIL

Introduction: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal-dominant systemic vascular disease that primarily involves small arteries. Patients with CADASIL experience migraines, recurrent ischemic strokes, cognitive decline, and dementia. The NOTCH3 gene, which is located on chromosome 19p13.12, is one of the disease-causing genes in CADASIL. Herein, we investigate the genetic and phenotypic features in a Chinese CADASIL family with heterozygous NOTCH3 mutation.Methods and Results: In the family, the proband suffered from dizziness, stroke, and cognitive deficits. Brain magnetic resonance imaging (MRI) demonstrated symmetrical white matter lesions in the temporal lobe, outer capsule, lateral ventricle, and deep brain. Whole-exome sequencing identified a known missense mutation in the proband, c.397C&gt;T (p.Arg133Cys), which was identified in his son and granddaughter using Sanger sequencing. The proband’s younger brother and younger sister also have a history of cognitive impairment or cerebral infarction, but do not have this genetic mutation, which may highlight the impact of lifestyle on this neurological disease.Conclusion: We identified a known CADASIL-causing mutation NOTCH3 (c.397C&gt;T, p.Arg133Cys) in a Chinese family. The clinical manifestations of mutation carriers in this family are highly heterogeneous, which is likely a common feature for the etiology of different mutations in CADASIL. Molecular genetic analyses are critical for accurate diagnosis, as well as the provision of genetic counselling for CADASIL

Seismic Anisotropic Fluid Identification in Fractured Carbonate Reservoirs

Seismic fluid identification plays an important role in reservoir exploration and development. Natural vertical fractures are common in carbonate rocks, it is essential to consider fracture-induced anisotropy in the fluid identification of fractured carbonate reservoirs. We have developed a novel Bayesian elastic impedance variation with an angle and azimuth (EIVAZ) inversion approach for directly estimating the fracture fluid indicator (FFI), which can avoid cumulative errors produced in the indirect calculation process. Under the assumption of weak anisotropy and a small incident angle, we first derive a new approximate PP-wave coefficient for horizontal transverse isotropic (HTI) media. Analysis shows that the new approximation has reasonable accuracy at angles of incidence less than 30°. To estimate the FFI from observed azimuthal P-wave seismic reflection data, we further deduce the azimuthal EI equation and establish a two-step inversion workflow. Finally, the proposed approach is demonstrated by tests on a synthetic data example and a field data set of a fractured carbonate reservoir in the Sichuan Basin (China). Results show that the model parameters can be reasonably estimated even with moderate noise levels. The estimated FFI and quasi-normal fracture weakness show relatively high values at the location of reservoirs, which reliably indicate a fractured gas-bearing reservoir

Seismic Anisotropic Fluid Identification in Fractured Carbonate Reservoirs

Seismic fluid identification plays an important role in reservoir exploration and development. Natural vertical fractures are common in carbonate rocks, it is essential to consider fracture-induced anisotropy in the fluid identification of fractured carbonate reservoirs. We have developed a novel Bayesian elastic impedance variation with an angle and azimuth (EIVAZ) inversion approach for directly estimating the fracture fluid indicator (FFI), which can avoid cumulative errors produced in the indirect calculation process. Under the assumption of weak anisotropy and a small incident angle, we first derive a new approximate PP-wave coefficient for horizontal transverse isotropic (HTI) media. Analysis shows that the new approximation has reasonable accuracy at angles of incidence less than 30&deg;. To estimate the FFI from observed azimuthal P-wave seismic reflection data, we further deduce the azimuthal EI equation and establish a two-step inversion workflow. Finally, the proposed approach is demonstrated by tests on a synthetic data example and a field data set of a fractured carbonate reservoir in the Sichuan Basin (China). Results show that the model parameters can be reasonably estimated even with moderate noise levels. The estimated FFI and quasi-normal fracture weakness show relatively high values at the location of reservoirs, which reliably indicate a fractured gas-bearing reservoir