SIZING OPTIMIZATION.

A method for structural member sizing optimization to be used for designing planar frames is presented. The procedure is based on the Augmented Lagrangian Multiplier method. The algorithm includes the displacements as state variables and consequently combines the analysis and the search for the optimal section properties into a single step. This combination process avoids the usual cycling between analysis and optimization phases. The width and height of rectangular elements are chosen from a finite compact set. The static equilibrium equations are treated as equality constraints eliminating the need to solve the standard structural analysis problem. The method handles displacement and stress limits as inequality constraints. Comparisons of performance and results are made with other optimization techniques

Comparison of tricuspid inflow and superior vena caval Doppler velocities in acute simulated hypovolemia: new non-invasive indices for evaluating right ventricular preload

BACKGROUND: Assessment of cardiac preload is important for clinical management of some emergencies related to hypovolemia. Effects of acute simulated hypovolemia on Doppler blood flow velocity indices of tricuspid valve (TV) and superior vena cava (SVC) were investigated in order to find sensitive Doppler indices for predicting right ventricular preload. METHODS: Doppler flow patterns of SVC and TV in 12 healthy young men were examined by transthoracic echocardiography (TTE) during graded lower body negative pressure (LBNP) of up to -60 mm Hg which simulated acute hypovolemia. Peak velocities of all waves and their related ratios (SVC S/D and tricuspid E/A) were measured, calculated and statistically analyzed. RESULTS: Except for the velocity of tricuspid A wave, velocities of all waves and their related ratios declined during volume decentralization. Of all indices measured, the peak velocities of S wave and AR wave in SVC correlated most strongly with levels of LBNP (r = -0.744 and -0.771, p < 0.001). CONCLUSION: The S and AR velocities are of good values in assessing right ventricular preload. Monitoring SVC flow may provide a relatively noninvasive means to assess direct changes in right ventricular preload

An integrated approach to determine left atrial volume, mass and function in hypertrophic cardiomyopathy by two-dimensional echocardiography

Methods: The study included 25 hypertrophic cardiomyopathy (HCM) patients (15 non-obstructive and 10 obstructive) and 25 controls for assessment of left atrial (LA) volume, mass and function by two-dimensional echocardiography. Measurement included mean LA diameter (LAD), LA mass = {(mean LAD + anterior LA wall + posterior LA wall)3- mean LAD3} × 0.8 + 0.6, LA volume = [(8/3 φ L ̇ A1 ̇ A2), where L is LA length, A1 and A2 are LA area in 4-chambers and 2-chambers, respectively] including maximum (Vmax), minimum (Vmin), and pre-atrial contraction (Vpre-A), total atrial stroke volume (TA-SV), TA emptying fraction (TA-EF), active atrial SV (AA-SV), AA-EF, passive atrial SV (PA-SV), PA-EF, atrial expansion index (AEI), and LA kinetic energy (LA-KE) = 1/2 × AA-SV × P × V2. Results: LAD, LA mass, Vmax, Vmin, and Vpre-Awere significantly higher in HCM than controls. TA-SV and TA-EF were comparable in both HCM subgroups and controls. AA-SV and LA-KE were significantly higher in both HCM subgroups than controls. LA-KE was significantly higher in obstructive HCM than non-obstructive (P < 0.001). PA-EF and AEI were significantly lower in obstructive HCM than controls (P < 0.05). Conclusion: HCM is associated with increased LA size and augmented LA pump function especially obstructive type. LA conduit and reservoir functions are impaired in obstructive HCM

Rapid assessment of myocardial infarct size in rodents using multi-slice inversion recovery late gadolinium enhancement CMR at 9.4T

Background: Myocardial infarction (MI) can be readily assessed using late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). Inversion recovery (IR) sequences provide the highest contrast between enhanced infarct areas and healthy myocardium. Applying such methods to small animals is challenging due to rapid respiratory and cardiac rates relative to T-1 relaxation.Methods: Here we present a fast and robust protocol for assessing LGE in small animals using a multi-slice IR gradient echo sequence for efficient assessment of LGE. An additional Look-Locker sequence was used to assess the optimum inversion point on an individual basis and to determine most appropriate gating points for both rat and mouse. The technique was applied to two preclinical scenarios: i) an acute (2 hour) reperfused model of MI in rats and ii) mice 2 days following non-reperfused MI.Results: LGE images from all animals revealed clear areas of enhancement allowing for easy volume segmentation. Typical inversion times required to null healthy myocardium in rats were between 300-450 ms equivalent to 2-3 R-waves and similar to 330 ms in mice, typically 3 R-waves following inversion. Data from rats was also validated against triphenyltetrazolium chloride staining and revealed close agreement for infarct size.Conclusion: The LGE protocol presented provides a reliable method for acquiring images of high contrast and quality without excessive scan times, enabling higher throughput in experimental studies requiring reliable assessment of MI

Left ventricular morphology and function in adolescents: Relations to fitness and fatness.

BACKGROUND: Obesity in childhood predisposes individuals to cardiovascular disease and increased risk of premature all-cause mortality. The aim of this study was to determine differences in LV morphology and function in obese and normal-weight adolescents. Furthermore, relationships between LV outcomes, cardiorespiratory fitness (CRF) and adiposity were explored. METHODS: LV morphology was assessed using magnetic resonance imaging (MRI) in 20 adolescents (11 normal-weight [BMI equivalent to 18kg/m(2)-25kg/m(2)] and 9 obese [BMI equivalent to ≥30kg/m(2)]); 13.3±1.1years, 45% female, Tanner puberty stage 3 [2-4]) using magnetic resonance imaging (MRI). Global longitudinal strain (GLS), strain rate (SR) and traditional echocardiographic indices were used to assess LV function. CRF (peak oxygen consumption), percent body fat (dual-energy x-ray absorptiometry), abdominal adipose tissue (MRI), and blood biochemistry markers were also evaluated. RESULTS: Adolescents with obesity showed significantly poorer LV function compared to normal-weight adolescents (P0.05). Moderate to strong associations between myocardial contractility and relaxation, adiposity, arterial blood pressure and cardiorespiratory fitness were noted (r=0.49-0.71, P<0.05). CONCLUSION: Obesity in adolescence is associated with altered LV systolic and diastolic function. The notable relationship between LV function, CRF and adiposity highlights the potential utility of multidisciplinary lifestyle interventions to treat diminished LV function in this population. CLINICAL TRIAL REGISTRATION: NCT01991106

Genetic background determines response to hemostasis and thrombosis

BACKGROUND: Thrombosis is the fatal and disabling consequence of cardiovascular diseases, the leading cause of mortality and morbidity in Western countries. Two inbred mouse strains, C57BL/6J and A/J, have marked differences in susceptibility to obesity, atherosclerosis, and vessel remodeling. However, it is unclear how these diverse genetic backgrounds influence pathways known to regulate thrombosis and hemostasis. The objective of this study was to evaluate thrombosis and hemostasis in these two inbred strains and determine the phenotypic response of A/J chromosomes in the C57BL/6J background. METHODS: A/J and C57Bl/6J mice were evaluated for differences in thrombosis and hemostasis. A thrombus was induced in the carotid artery by application of the exposed carotid to ferric chloride and blood flow measured until the vessel occluded. Bleeding and rebleeding times, as surrogate markers for thrombosis and hemostasis, were determined after clipping the tail and placing in warm saline. Twenty-one chromosome substitution strains, A/J chromosomes in a C57BL/6J background, were screened for response to the tail bleeding assay. RESULTS: Thrombus occlusion time was markedly decreased in the A/J mice compared to C57BL/6J mice. Tail bleeding time was similar in the two strains, but rebleeding time was markedly increased in the A/J mice compared to C57BL/6J mice. Coagulation times and tail morphology were similar, but tail collagen content was higher in A/J than C57BL/6J mice. Three chromosome substitution strains, B6-Chr5(A/J), B6-Chr11(A/J), and B6-Chr17(A/J), were identified with increased rebleeding time, a phenotype similar to A/J mice. Mice heterosomic for chromosomes 5 or 17 had rebleeding times similar to C57BL/6J mice, but when these two chromosome substitution strains, B6-Chr5(A/J )and B6-Chr17(A/J), were crossed, the A/J phenotype was restored in these doubly heterosomic progeny. CONCLUSION: These results indicate that susceptibility to arterial thrombosis and haemostasis is remarkably different in C57BL/and A/J mice. Three A/J chromosome substitution strains were identified that expressed a phenotype similar to A/J for rebleeding, the C57Bl/6J background could modify the A/J phenotype, and the combination of two A/J QTL could restore the phenotype. The diverse genetic backgrounds and differences in response to vascular injury induced thrombosis and the tail bleeding assay, suggest the potential for identifying novel genetic determinants of thrombotic risk

Left ventricular diastolic function is strongly correlated with active emptying of the left atrium: a novel analysis using three-dimensional echocardiography

BACKGROUND: Increased left atrial (LA) dimensions are known to be a risk factor in predicting cardiovascular events and mortality and to be one key diagnostic tool to assess diastolic dysfunction. Currently, LA measurements are usually conducted using 2D-echocardiography, although there are well-known limitations. Real-time 3D-echocardiography is able to overcome these limitations, furthermore being a valid measurement tool compared to reference standards (e.g. cardiac magnetic resonance imaging). We investigated LA function and volume and their association to left ventricular (LV) diastolic function, using newly designed and validated software for 3D-echocardiographic analysis. This software is the first to allow for a sophisticated analysis of both passive and active LA emptying. METHODS: We analyzed 2D- and 3D-echocardiographic measurements of LA volume and function in 56 subjects and compared the results between patients with normal LV diastolic function (NDF) (n = 30, 52 ± 15 years, BMI 24.7 ± 2.6 kg/m(2)) and patients in which diastolic dysfunction (DDF) was suspected (n = 26, 65 ± 9 years, BMI 26.7 ± 3.7 kg/m(2)). RESULTS: Volumes during LA active emptying were significantly smaller in DDF compared to NDF (active atrial stroke volume (ASV): 3.0 (0.1–4.5) vs. 5.5 (2.7–7.8) ml, p = 0.005; True-EF: 7.3(0.1–11.5) vs. 16.2 (8.1–25.4) %, p = 0.002). Furthermore, ASV showed a stronger association to E/e’(mean) than all other measured LA volumes (β = − 0.35, p = 0.008). Neither total stroke LA volume, nor maximum or minimum LA volume differed significantly between the groups. CONCLUSIONS: Diastolic LV dysfunction results in a reduction in active LA emptying, which is more strongly associated with LV filling pressure than other previously investigated LA parameters

Losartan Decreases p42/44 MAPK Signaling and Preserves LZ+ MYPT1 Expression

Heart failure is associated with impairment in nitric oxide (NO) mediated vasodilatation, which has been demonstrated to result from a reduction in the relative expression of the leucine zipper positive (LZ+) isoform of the myosin targeting subunit (MYPT1) of myosin light chain phosphatase. Further, captopril preserves normal LZ+ MYPT1 expression, the sensitivity to cGMP-mediated vasodilatation and modulates the expression of genes in the p42/44 MAPK and p38 MAPK signaling cascades. This study tests whether angiotensin receptor blockade (ARB) with losartan decreases p42/44 MAPK or p38 MAPK signaling and preserves LZ+ MYPT1 expression in a rat infarct model of heart failure. In aortic smooth muscle, p42/44 MAPK activation increases and LZ+ MYPT1 expression falls after LAD ligation. Losartan treatment decreases the activation of p42/44 MAPK to the uninfarcted control level and preserves normal LZ+ MYPT1 expression. The expression and activation of p38 MAPK, however, is low and does not change following LAD ligation or with losartan therapy. These data suggest that either reducing or blocking the effects of circulating angiotensin II, both decreases the activation of the p42/44 MAPK signaling cascade and preserves LZ+ MYPT1 expression. Thus, the ability of ACE-inhibitors and ARBs to modulate the vascular phenotype, to preserve normal flow mediated vasodilatation may explain the beneficial effects of these drugs compared to other forms of afterload reduction in the treatment of heart failure

Age-Related Impairment of Ultrasonic Vocalization in Tau.P301L Mice: Possible Implication for Progressive Language Disorders

Tauopathies, including Alzheimer's Disease, are the most frequent neurodegenerative diseases in elderly people and cause various cognitive, behavioural and motor defects, but also progressive language disorders. For communication and social interactions, mice produce ultrasonic vocalization (USV) via expiratory airflow through the larynx. We examined USV of Tau.P301L mice, a mouse model for tauopathy expressing human mutant tau protein and developing cognitive, motor and upper airway defects.At age 4-5 months, Tau.P301L mice had normal USV, normal expiratory airflow and no brainstem tauopathy. At age 8-10 months, Tau.P301L mice presented impaired USV, reduced expiratory airflow and severe tauopathy in the periaqueductal gray, Kolliker-Fuse and retroambiguus nuclei. Tauopathy in these nuclei that control upper airway function and vocalization correlates well with the USV impairment of old Tau.P301L mice.In a mouse model for tauopathy, we report for the first time an age-related impairment of USV that correlates with tauopathy in midbrain and brainstem areas controlling vocalization. The vocalization disorder of old Tau.P301L mice could be, at least in part, reminiscent of language disorders of elderly suffering tauopathy