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Abstract-Left ventricular hypertrophy (LVH) is associated with electric remodeling and increased arrhythmia risk, although the underlying mechanisms are poorly understood. In the experiments here, functional voltage-gated (Kv) and inwardly rectifying (Kir) K ϩ channel remodeling was examined in a mouse model of pressure overload-induced LVH, produced by transverse aortic constriction (TAC). Action potential durations (APDs) at 90% repolarization in TAC LV myocytes and QT c intervals in TAC mice were prolonged. Mean whole-cell membrane capacitance (C m ) was higher, and I to,f , I K,slow , I ss , and I K1 densities were lower in TAC, than in sham, LV myocytes. Although the primary determinant of the reduced current densities is the increase in C m , I K,slow amplitudes were decreased and I ss amplitudes were increased in TAC LV cells. Further experiments revealed regional differences in the effects of LVH. Cellular hypertrophy and increased I ss amplitudes were more pronounced in TAC endocardial LV cells, whereas I K,slow amplitudes were selectively reduced in TAC epicardial LV cells. Consistent with the similarities in I to,f and I K1 amplitudes, Kv4.2, Kv4.3, and KChIP2 (I to,f ), as well as Kir2.1 and Kir2.2 (I K1 ), transcript and protein expression levels were similar in TAC and sham LV. Unexpectedly, expression of I K,slow channel subunits Kv1.5 and Kv2.1 was increased in TAC LV. Biochemical experiments also demonstrated that, although total protein was unaltered, cell surface expression of TASK1 was increased in TAC LV. Functional changes in repolarizing K ϩ currents with LVH, therefore, result from distinct cellular (cardiomyocyte enlargement) and molecular (alterations in the numbers of functional channels) mechanisms. (Circ Res. 2008;102:1406-1415.)Key Words: hypertrophy Ⅲ arrhythmia Ⅲ heart failure L eft ventricular hypertrophy (LVH) is an adaptive response of the myocardium to an increase in load. 1 LVH is seen in various disease states including hypertension and myocardial infarction, as well as in valvular and congenital heart diseases. 1 LVH is also observed in physiological states following rigorous, prolonged exercise. 2 Although physiological LVH does not confer increased morbidity and mortality, pathological LVH is consistently associated with prolongation of ventricular action potentials and alterations in the dispersion of repolarization, both of which result in electric instability and increase the propensity to develop lifethreatening arrhythmias. 3 Several lines of evidence suggest that these electric changes reflect, at least in part, alterations in the functioning of the K ϩ channels that underlie ventricular action potential repolarization. 3,4 Various experimental models of LVH, 5-7 including pressure overload-induced LVH, 8,9 have been developed to explore the mechanisms underlying K ϩ current remodeling.Although several studies have examined regional differences in remodeling, 8 -11 few have probed the underlying molecular and cellular mechanisms. In the studies here, a mouse mo...

Nonsyndromic craniosynostosis is often associated with cognitive, speech, and/or behavioral abnormalities. The etiopathology of this association is unknown. Furthermore, the proportion of children diagnosed with cognitive and behavioral dysfunction increases with age. Therefore, longitudinal cognitive, behavioral, and speech assessment and treatment are integral to the care of these patients.

Rationale and Objectives CT section thickness and reconstruction kernel each influence CT measurements of emphysema. This study was performed to assess whether their effects are related to the magnitude of the measurement. Materials and Methods Low-radiation-dose multidetector CT was performed in 21 subjects representing a wide range of emphysema severity. Images were reconstructed using 20 different combinations of section thickness and reconstruction kernel. Emphysema index values were determined as the percentage of lung pixels having attenuation lower than multiple thresholds ranging from −960 HU to −890 HU. The index values obtained from the different thickness-kernel combinations were compared by repeated measures ANOVA and Bland-Altman plots of mean vs. difference, and correlated with quantitative histology (mean linear intercept, Lm) in a subset of resected lung specimens. Results The effects of section thickness and reconstruction kernel on the emphysema index were significant (p<0.001) and diminished as the index threshold was raised. The changes in index values due to changing the thickness-kernel combination were largest for subjects with intermediate index values (10–30%), and became progressively smaller for those with lower and higher index values. This pattern was consistent regardless of the thickness-kernel combinations compared and the HU threshold used. Correlations between the emphysema index values obtained with each thickness-kernel combination and Lm ranged from r=0.55–0.68 (p=0.007–0.03). Conclusion The effects of CT section thickness and kernel on emphysema index values varied systematically with the magnitude of the emphysema index. All reconstruction techniques provided significant correlations with quantitative histology.

The mass measurement is more accurate, less variable, and more reproducible in coronary calcium quantification than are measurements with other algorithms. Accurate quantification of calcium in each calcified plaque may require that the threshold be set individually, depending on the calcium density.

Background-Atherosclerotic plaques may rupture without warning and cause acute cardiovascular syndromes such as heart attack and stroke. Methods to assess plaque vulnerability noninvasively and predict possible plaque rupture are urgently needed.Method-MRI-based three-dimensional unsteady models for human atherosclerotic plaques with multi-component plaque structure and fluid-structure interactions are introduced to perform mechanical analysis for human atherosclerotic plaques.Results-Stress variations on critical sites such as a thin cap in the plaque can be 300% higher than that at other normal sites. Large calcification block considerably changes stress/strain distributions. Stiffness variations of plaque components (50% reduction or 100% increase) may affect maximal stress values by 20-50 %. Plaque cap erosion causes almost no change on maximal stress level at the cap, but leads to 50% increase in maximal strain value.Conclusions-Effects caused by atherosclerotic plaque structure, cap thickness and erosion, material properties, and pulsating pressure conditions on stress/strain distributions in the plaque are quantified by extensive computational case studies and parameter evaluations. Computational mechanical analysis has good potential to improve accuracy of plaque vulnerability assessment.1 Corresponding

BACKGROUND AND PURPOSE:Thromboembolic events are the most common complications of elective coil embolization of cerebral aneurysms. Administration of oral clopidogrel and/or aspirin could lower the thromboembolic complication rate.