Load Dependent Research Articles

Cardiac contractility index, a novel biomarker of incident heart failure amongst people with normal left ventricular ejection fraction in the UK Biobank

Abstract Background Cardiac contractility index (CCI) is a simple non-invasive measure of myocardial contractility defined by systolic blood pressure divided by indexed left ventricular end-systolic volume. Although left ventricular ejection fraction (LVEF) is essential for phenotyping patients with suspected heart failure (HF), it is load dependent and insensitive to subtle subclinical ventricular dysfunction. Left ventricular (LV) strain, although more sensitive at detecting subtle disturbances in myocardial function, also does not reflect loading conditions and dependency on image quality and inter-vendor variability limit widespread use. The ability of CCI to identify patients with subclinical left ventricular dysfunction at risk of developing HF is unknown. Purpose We aimed to: 1) explore the relationship between CCI with conventional imaging biomarkers of LV systolic dysfunction and 2) assess whether CCI could identify those at increased risk of incident HF in people without pre-existing left ventricular dysfunction in the UK Biobank imaging study. Methods We explored the relationship between CCI and laboratory and imaging biomarkers of systolic function, including LVEF and LV strain. Scatter plots were constructed for CCI with LVEF and LV strain. Pearson’s coefficients (r) and coefficient of determination (r2) were calculated to assess for correlations. People with sex-specific thresholds of abnormally low LVEF derived from within the same cohort (<48% for men, and <51% for women) were then excluded. CCI was then dichotomised as being high or low based its median value (4.4 mmHg/ml/m2). Age-sex adjusted Cox proportional hazards ratios (HR) with 95% CIs were estimated for the primary outcome of incident HF (derived from linked national digital registries) in addition to modelling with restricted cubic splines. Results We included 38,215 people (median age 55 years, 48% men). There was moderate correlation between CCI with LVEF (r=0.53 [0.53-0.54], R2=0.29; p<0.001), LV global circumferential strain (r=-0.50 [-0.50- -0.49], R2=0.25; p<0.001) and radial strain (r=-0.49 [0.48-0.50], R2=0.24; p<0.001), although was only weekly correlated with LV global longitudinal strain (r=-0.19 [-0.20- -0.18], R2=0.03; p<0.001) (Figure 1A). Using sex-specific thresholds 33,739 (88.3%) had a normal LVEF. During 195,584 person-years of follow-up (median 5.5 years), a total of 221 (0.7%) participants developed HF. Age-sex adjusted low CCI at baseline was associated with an increased risk of incident HF (adjusted HR 1.33 [1.01-1.75]; p=0.043). The association between CCI and incident HF was curvilinear (Figure 1B). Conclusions CCI identifies people with subclinical left ventricular systolic dysfunction at risk of developing incident heart failure.

Cardiac myosin's mechanics and load dependent kinetics are not altered by the thin-filament proteins.

The force necessary to power human heart contraction is generated by beta cardiac myosin pulling on regulated thin filaments. Myosin's force generation is a tightly regulated process, and its disruption causes diseases including genetic cardiomyopathies. Deciphering the details of force generation at the molecular scale is critical for our understanding of both cardiac physiology and disease. While excellent studies have elucidated the mechanics and kinetics underlying the interactions between cardiac myosin and actin at the single molecule scale, the majority of these studies have been conducted in the absence of regulatory proteins. In the case of several other myosin isoforms, regulatory proteins alter the mechanics and load-dependent kinetics of the myosin working stroke, and it is not clear what role, if any they play in tuning the cardiac myosin working stroke and load-dependent kinetics. Here, we used a single molecule optical trapping assay to measure myosin's mechanics in the presence and absence of reconstituted thin-filaments (RTFs). We observed that regulatory proteins do not affect the myosin working stroke or its substeps. Interestingly, at low ATP, we observed that regulatory proteins slow the rate of actomyosin dissociation, and we showed using stopped flow kinetics that this is due to tuning of the rate of ATP-induced dissociation. The difference in the dissociation rate disappears at physiologically relevant ATP concentrations. We also used an isometric force clamp to investigate the load dependence of the myosin working stroke at physiologically relevant ATP concentrations, and this was also unchanged with RTFs. Taken together, these results show that cardiac myosin's mechanics are not altered by regulatory proteins at physiologically relevant ATP concentrations, and they provide important insights into the molecular mechanisms underlying heart contraction.

1060 HOW TO EVALUATE RIGHT VENTRICULAR FUNCTION IN PATIENTS WITH SIGNIFICANT TRICUSPID REGURGITATION: PRELIMINARY DATA BEFORE AND AFTER TRICLIP IMPLANTATION

Abstract Objective transcatheter tricuspid valve repair (TTVR) has recently become available as a treatment option for patients with symptomatic significant tricuspid regurgitation (TR) not eligible for tricuspid valve surgery. In the absence of a single reliable measure of the RV systolic function, a number of surrogate echocardiographic parameters have been proposed for clinical use (tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (FAC), peak S wave velocity of the lateral tricuspid annulus by tissue Doppler imaging (S’ RV-TDI) and RV 2D-FWS. At present, TTVR is not recommended in patients with severe PH and poor RV function, but exact cut-offs when TTVR should be rejected are lacking. Aim of this study was to assess RV function before and after Triclip implantation. Materials and methods from June 2021 to June 2022 clinical and echocardiographic data of 8 patients with TR who underwent TTVR intervention in our division were evaluated for RV function. TAPSE, FAC, S’RV-TDI, RV GS and RV FWS at baseline and 1 month of follow up were assessed. Continuous variables are presented as mean ± standard deviation (SD). Categorical variables were presented as frequencies and percentages. Results the mean values of RV function assessed before and after Triclip implantation were respectively (18,75 mm± 4,04 vs 18,38 mm ± 3,34) for TAPSE, (10,50 cm/sec± 2,33 vs 10,38 cm/sec ± 1,19) for S’ RV-TDI, (38% ± 0,05 vs 37% ± 0,04) for FAC, and (-17% ± 0,03 vs -19% ± 0,02) for RV FWS. The number of patients that show at baseline RV dysfunction, according to the cut-offs indicated from guidelines, were 4 for TAPSE; 3 S’ RV-TDI; 1 for FAC and 7 for RV 2D-FWS. At 1 month of follow-up, patients with ventricular dysfunction were respectively 3,2,2,4. Conclusions in the presence of significant TR, the accurate assessment of RV function becomes even more challenging as a result of the load and angle dependency of TAPSE, RVFAC. Significant TR results in a reduction in RV afterload, which may preserve the aforementioned markers of RV function even when contractility is impaired. Probably RV 2D-STE is less angle and load dependent than traditional RV function indices and less confounded by RV geometry and passive motion.

785 ACCURATE ASSESSMENT OF RIGHT VENTRICULAR FUNCTION BECOMES MORE CHALLENGING IN PATIENTS WITH SEGNIFICANT TRICUSPID REGURGITATION: A CASE REPORT OF RIGHT VENTRICULAR DYSFUNCTION AFTER TRICLIP IMPLANTATION

Abstract Introduction anatomically and functionally different from the left ventricle, the right ventricle (RV) plays an increasingly recognized role in determining symptoms and outcomes in multiple conditions. Due to RV complex anatomy and mechanics, the evaluation of its size and function is challenging. The ideal imaging technique should be capable of comprehensive, accurate and reproducible assessment of RV morphology and contraction. In the absence of a single reliable 2DE measure of the RV systolic function, several surrogate echocardiographic parameters have been proposed for clinical use, from one-dimensional (TAPSE) to 3D techniques. Clinical Case we report a case of an 82-year-old female patient who was admitted to our hospital because of dyspnoea, with a history of atrial fibrillation, hypertension, diabetes mellitus, chronic kidney disease, and a last year hospitalization for heart failure. A transthoracic echocardiography (TTE) was performed, showing a high-grade tricuspid valve regurgitation. Further investigation using transoesophageal echocardiography (TEE) showed, in four chambers view, dilatation of right sections and confirm TR was significant, so screening for TriClip implantation was performed. The exam was diagnostic for massive TR, moderate Mitral Regurgitation, and the estimated PAPs about 50 mmHg, so, in the absence of anatomical exclusion elements, severe pulmonary hypertension and poor RV function, transcatheter treatment with TriClip was offered. We had evaluated RV function, obtaining a FAC about normal limit (which should be corrected by valvular regurgitation), and a reduced Strain value. The patient received an edge-to-edge reparation of the tricuspid valve using the TriClip XTR (Clip) system with 2 clips placed. The post-interventional echocardiographic results were an optimal correction of valvular regurgitation, with, however, a clear right ventricular disfunction. Those finding were confirmed by further echocardiographic follow up exams, even during inotropic treatment by low dobutamine dose. Conclusion estimating RV function remains challenging because of the complex geometry of the RV. In the presence of significant TR, the accurate assessment of RV function becomes even more challenging because of the load and angle dependency of TAPSE, RVFAC and RVEF. Significant TR result in a reduction in RV afterload, which may preserve the markers of TV function even when contractility is impaired. 2d-STE in less angle and load dependent than traditional RV function indices and less confounded by RV geometry and passive motion.

Abstract 10787: Carotid Artery Stiffness Mechanisms Associated With End Organ Damage and All-Cause Mortality: The Multi-Ethnic Study of Atherosclerosis (mesa)

Introduction: Stiff arteries increase the risk of end organ damage to the brain and kidneys. Arterial stiffness can be separated into two main mechanisms: 1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to remodeling of the vessel wall. The relationship between arterial stiffness mechanisms and end organ damage risk is unknown. Hypothesis: Both stiffness mechanisms will be significantly associated with chronic kidney disease (CKD), dementia, and mortality. Methods: MESA participants with B-mode carotid ultrasound in 2000-2002 were included in this study (n=6147). Carotid pulse wave velocity (cPWV) was calculated to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 BP with participant-specific models. Load dependent (LD) stiffness was the difference of total and structural stiffness. Associations with incident CKD, dementia defined by ICD codes, and mortality were assessed with Cox models adjusted for age, sex, race/ethnicity, education, study site, smoking, pack-years, diabetes, BMI, SBP, non-HDL-C, BP medication, and lipid medication. Results: During 14.3±4.8 years of follow-up, 773 CKD events, 535 dementia events, and 1529 deaths occurred. Total cPWV was associated with mortality (HR 1.04 [1.01-1.08], p=0.02) and dementia (HR 1.06 [1.01 - 1.12], p=0.03). Structural cPWV was significantly associated with mortality (HR 1.04 [1.00 - 1.08], p=0.04) but not CKD (HR 1.00 [0.94-1.05], p=0.86) or dementia (HR 1.06 [0.99-1.13], p=0.06). LD cPWV was associated with CKD (HR 1.38 [1.17 - 1.63], p<0.001) but not mortality (HR 1.11 [0.99-1.25], p=0.07) or dementia (HR 1.14 [0.94-1.38], p=0.19). Conclusions: Structural carotid artery stiffness was significantly associated with all-cause mortality, while LD stiffness was significantly associated with CKD. Total carotid stiffness was associated with incident dementia but LD and structural stiffness mechanisms were not.

Comparison of Joint-Level Kinetics During Single-Leg and Double-Leg Weightlifting Derivatives.

Hayashi, R, Yoshida, T, and Kariyama, Y. Comparison of joint-level kinetics during single- and double-leg weightlifting derivatives. J Strength Cond Res 37(5): 1017-1022, 2023-Humans have different 3-dimensional biomechanical characteristics of the lower extremities during locomotion with one and both legs. These biomechanical characteristics may also be observed in the weightlifting derivatives. This study aimed to compare the 3-dimensional joint kinetics of the lower extremities during the single-leg hang power clean (SHPC) and double-leg hang power clean (DHPC). Ten male track and field athletes performed the SHPC and DHPC using external loads of 30, 60, and 90% of one repetition maximum (1RM). The 1RMs in SHPC and DHPC were measured separately, and the external loads at 30, 60, and 90% of the 1RM used were determined based on the different 1RMs in SHPC and DHPC. We calculated the joint moment and joint power of the SHPC and DHPC using a motion capture system and force platforms. The hip abduction moment and power of the SHPC were significantly greater than those of the DHPC under all external loads ( p < 0.05). In addition, ankle joint moment at all external loads and joint power at 90% of 1RM was greater for SHPC than for DHPC ( p < 0.05). Furthermore, although hip (extension-flexion) and ankle joint kinetics in SHPC and DHPC showed similar load dependence, hip abduction axis kinetics was not load dependent. These results suggest that the hip (abduction-adduction) and ankle joint kinetics in SHPC are greater than in DHPC, but hip (abduction-abduction) kinetics in SHPC is not load independent.

Abstract P340: Associations Of Life’S Simple 7 And 10-year Change In Load-dependent Arterial Stiffness: The Multi-ethnic Study Of Atherosclerosis (mesa)

Introduction: Arterial stiffness can be separated into two main mechanisms: 1) load-dependent (LD) stiffening from higher blood pressure (BP) and (2) structural stiffening due to changes in the vessel wall. Structural stiffening is strongly associated with advancing age. LD stiffening is highly variable and is more strongly associated with CVD. Hypothesis: Optimal Life’s Simple 7 factors will be associated with a slower rate of increase in LD stiffness. Methods: MESA participants with carotid ultrasound at Exam 1 and Exam 5 (year 10) were included (n=2557). Peterson’s elastic modulus (PEM) was calculated to represent total stiffness. Structural stiffness was PEM adjusted to a standard BP of 120/80 mmHg using participant-specific models. LD stiffness was the difference between total and structural stiffness. Changes in stiffness mechanisms over 10 years for poor versus optimal Life’s Simple 7 (LSF) factors were compared with linear models adjusted for age, sex, race/ethnicity, study site, education, BP and lipid medication, C-reactive protein, Interleukin-6, and baseline stiffness. Results: No LS7 factors was associated with increased LD stiffening for the whole cohort. For the bottom quartile of baseline LD stiffness, smoking (2.55±1.23 kPa, p=0.039) was associated with increased LD stiffening. For the highest quartile of baseline LD stiffness, no LS7 factors were significantly associated with stiffening. Conclusion: Smoking was associated with increased LD stiffening in those with low baseline stiffness. Smoking cessation and prevention may be especially important in these individuals to promote healthy vascular aging.

Electrified Drive-Unit Parametric Mechanical-Loss Model Development and Calibration

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;As the automotive industry vies to meet progressively more stringent global CO2 regulations in a cost-effective manner, electrified drive system cost and losses must be reduced. To this end, a parametric Drive Unit (DU) mechanical-loss model was developed to aid in the design and development of electrified propulsion systems, where the total propulsion system cost and DU losses can be directly linked (e.g., Hybrid Electric Vehicle (HEV) motor/inverter/engine content, or Battery Electric Vehicle (BEV) battery size).&lt;/div&gt;&lt;div class="htmlview paragraph"&gt;Many DUs for electrified propulsion systems are relatively “simple” drive systems, consisting of gears, bearings, shafts, lip seals, and an electric motor(s), but without clutches, high-pressure lube systems, or chains/belts as found in conventional automatic transmissions. The DU loss model described in this paper studies these simple DUs, with the mechanical losses dissected into 10 loss components.&lt;/div&gt;&lt;div class="htmlview paragraph"&gt;Analysis was conducted at the vehicle level to assess the relative loss contributions of the DU, motors, engine, etc. for the entire vehicle propulsion system to show the DU loss contribution to the total system. The DU loss model was used to deconstruct the total DU mechanical loss into subcomponents of Speed-Dependent (SD) and Load-Dependent (LD) losses. For each loss component, standard loss model equations were modified, or new equations were created, and calibrated based on loss data/trends of component-level bench tests, supplier data, and/or DU-level tests. Particular emphasis was placed on the LD components of the gear and bearing losses, as a function of load, speed and temperature, as they can represent a large portion of the total DU loss. DU-level tests were conducted at various positive and negative (regenerative braking) loads, speeds, fluid types, temperatures, and sump-fill levels to aid the development of the model. The model calibration methodology is described, where the calibrations of some of the individual component models were iterated, so that a universal set of loss model calibrations produced loss results that closely matched the test DU losses at the various operating conditions.&lt;/div&gt;&lt;/div&gt;

Assessment of load dependent friction coefficients and their influence on spur gears efficiency

Traditional procedures to calculate efficiency on gear transmissions generally consider sliding friction as the only dissipative effect, and what is more, they are based on the usage of constant friction coefficients. Although this approach gives acceptable efficiency values depending on the transmission application, the utilisation of a variable friction coefficient provides more reliable results of the friction behavior. Within this framework, the influence of the choice of the friction coefficient on the efficiency of shifted spur gears is assessed in this study. The Niemann’s friction coefficient formulation, which is constant and commonly applied to traditional approaches, was implemented in this proposal, in order to compare it with two hybrid formulations, which are based on elastohydrodynamic lubrication fundamentals and capable to reproduce the friction coefficient in dry contact, boundary, mixed and fluid film conditions of lubrication. These friction coefficient formulations are dependent on the load applied in the conjunction, therefore an enhanced load sharing allows for a better modelling of sliding friction, not only because it depends directly on the normal forces, but due to the friction coefficient load dependence. In this regard, the Load Contact Model previously developed by the authors, which considers the deflections of the adjacent teeth and shifting profile to calculate the load sharing and the friction coefficient, is used, allowing for efficiency values with a high level of accuracy. The efficiency results obtained when hybrid formulations are implemented provides lower values than those determined including Niemann’s formulation. Furthermore, there is a shifting profile which makes optimal the efficiency. This shift factor depends on the implemented friction coefficient formulation, concluding the remarkable importance of the friction coefficient choice.

Decrement of crack propagation in bulk Bi-2223 superconducting ceramics with Sn-diffusion annealing temperature

The effect of Sn diffusion at different annealing temperature on the Bi1.8Pb0.4Sr2.0Ca2.1Cu3.0Oy superconducting materials is performed with the aid of Vickers microhardness (H v ) measurements at different applied loads in the range of 0.245–2.940 N. The measurement results observed show that all the samples exhibit typical indentation size effect behavior, meaning that both the elastic and plastic deformations play dominant role on the inorganic structures owing to the presence of the elastic recovery. Likewise, the mechanical characteristics increase with the Sn additives as a consequence of improvement of the local structural distortions and boundary weak-links between the grains. Furthermore, the increased Sn inclusions in the crystal lattice make the cracks propagate slower than before. This may be related to the fact that the Sn particles prefer to accumulate throughout the grain boundaries (defect locations) similar to the propagation of the cracks in the materials. In other words, the ductility (nondirectional interactions) of the ceramics tends to improve with the increment in the Sn concentration level in the crystal lattice as a consequence of the enhancement of the tensile strength, fracture toughness and especially Griffith critical crack length values. Hence, the mechanical flexibility takes place rapidly in the crystal structure. Moreover, the hardness measurements allow us to discuss the load dependent and independent microhardness, elastic modulus, yield strength and fracture toughness parameters. At the same time, the experimental data of the Vickers hardness are studied by the available models regarding Meyer’s law, proportional sample resistance model, elastic–plastic deformation model and Hays–Kendall (HK) approach for the first time. According to the results obtained, the load dependence of Vickers microhardness is fitted with the HK approach rather than the other methods. Based on the electrical and superconducting results observed before, it is to be mentioned here that the significant improvement of electrical performance may contribute to enhancement in mechanical characteristics.

Microhardness studies of sulfamic acid single crystal

Vicker's microhardness study of (100), (010) and (001) faces of a non-linear optical crystal sulfamic acid have been reported. Single crystals of sulfamic acid have been grown by slow evaporation method. The load dependence of the Vickers microhardness of sulfamic acid crystal were investigated and analyzed from the stand point of various theoretical models. Crystal samples in a, b and c-axes exhibit reverse indentation effect which is best described by Meyer's law, Hays-Kendall's approach and proportional specimen resistance (PSR) models. The negative values of load dependent quantities in Hays-Kendall's approach and PSR model suggest that the origin of indentation size effect is associated with the process of relaxation of indentation stresses.

Load dependency in force–length relations in isolated single cardiomyocytes

The previously reported pressure–volume (PV) relationship in frog hearts shows that end-systolic PV relation (ESPVR) is load dependent, whereas ESPVR in canine hearts is load independent. To study intrinsic cardiac mechanics in detail, it is desirable to study mechanics in a single isolated cardiomyocyte that is free from interstitial connective tissue. Previous single cell mechanics studies used a pair of carbon fibers (CF) attached to the upper surface of opposite cell ends to stretch cells. These studies showed that end-systolic force–length (FL) relation (ESFLR) is load independent. However, the range of applicable mechanical load using the conventional technique is limited because of weak cell-CF attachment. Therefore, the behavior of ESFLR in single cells under physiologically possible conditions of greater load is not yet well known. To cover wider loading range, we contrived a new method to hold cell-ends more firmly using two pairs of CF attached to both upper and bottom surfaces of cells. The new method allowed stretching cells to 2.2 μm or more in end-diastolic sarcomere length. ESFLR virtually behaves in a load independent manner only with end-diastolic sarcomere length less than 1.95 μm. It exhibited clear load dependency with higher preload, especially with low afterload conditions. Instantaneous cellular elastance curves showed that decreasing afterload enhanced relaxation and slowed time to peak elastance, as previously reported. A simulation study of a mathematical model with detailed description of thin filament activation suggested that velocity dependent thin filament inactivation is crucial for the observed load dependent behaviors and previously reported afterload dependent change in Ca2+ transient shape.

Finite element analysis of equine incisor teeth. Part 1: Determination of the material parameters of the periodontal ligament

In equine dentistry, periodontal diseases are frequently found in aged horses. Excessive strains and stresses within the periodontal ligament (PDL) occurring during the masticatory cycle may be predisposing factors especially in old horses with short, worn teeth. The finite element (FE) analysis is a valuable tool to investigate such strains and stresses in biological materials but a precondition for a realistic and reliable FE analysis is accurate knowledge of material parameters. As no data exist concerning the PDL of equine incisor teeth, this study was undertaken to determine the equine specific, age related and load dependent Young’s modulus of equine incisors.To determine the biomechanical behaviour of the PDL, the incisor jaw-regions of horses of different ages were sectioned into 5mm thick slice samples and the incisors experimentally intruded (i.e. axially displaced into the alveolus) while recording the load–displacement relationship. Based on high resolution micro-computer tomography (μCT)-datasets, reliable and detailed 3-dimensional models of the slice samples were constructed focusing on precisely modelling the anatomy of the PDL. FE calculations were then performed and set-actual comparisons of the FE results with the experimentally measured displacements enabled the Young’s modulus of the PDL to be determined.The results of this study reflect the typical non-linear behaviour of the collagen fibres of the PDL and present a high load dependency of the PDL’s Young’s modulus. Further investigations calculating the strains and stresses within the periodontal ligament, teeth and surrounding bone of the entire rostral aspect of the jaw are warranted.

Microstructure and size effect in ultrafine (Ti0.705Fe0.295)100−xSnx (0⩽x⩽4at.%) composites

Abstract The effect of Sn addition on the microstructure evolution in ultrafine lamellar (Ti0.705Fe0.295)100−xSnx (0 ⩽ x ⩽ 4 at.%) eutectic composites and size effect during Vickers microhardness measurements at load in the range of 0.049 N and 19.61 N have been studied. The hardness of all the lamellar composites with varying Sn content decreases with increase of applied load pointing the existence of normal indentation size effect (ISE). The load dependence microhardness values have been analysed using existing models such as, Meyer’s law, depth dependence hardness model, proportional specimen resistance model (PSR), modified PSR model, Hays-Kendall approach, and elastic–plastic deformation model. Furthermore, the load dependent microhardness has been correlated with the dislocation density, microstructure length-scale, and ISE. The microscopic mechanisms of ISE and strain hardening behaviour in lamellar eutectic composite have been explored.

Immediate Impact of Successful Percutaneous Mitral Valve Commissurotomy on Echocardiographic Measures of Right Ventricular Contractility

Functional analysis of the right ventricle cannot be reliably evaluated by conventional echocardiography, because of its complex geometry and load dependence of ejection phase indices. The Tei index, dP/dt, and myocardial acceleration during isovolumic contraction are parameters of right ventricular (RV) contractility unaffected by RV geometry. However, the effect of loading conditions on these parameters is controversial. The aim of this study was to examine how afterload reduction observed after percutaneous transverse mitral commissurotomy (PTMC) in patients with mitral stenosis affects these measures of RV contractility. Fifty-eight patients (mean age, 30.0 ± 8.3 years seven men, 52 women) with isolated rheumatic mitral stenosis, eight of whom had atrial fibrillation, were studied prospectively before and 24 to 48 hours after PTMC. Immediately after PTMC, mitral valve area increased from 1.0 ± 0.2 to 1.8 ± 0.3 cm(2) (P= .0001). There was a significant decrease in systolic pulmonary artery pressure from 50.2 ± 26.9 to 33.2 ± 12.3 mm Hg (P=.0001), a decrease in the RV Tei index from 0.5 ± 0.2 to 0.3 ± 0.2 (P= .0001), and an increase in RV dP/dt from 321.0 ± 59.9 to 494.6 ± 139.5 mm Hg/sec (P= .0001). RV myocardial acceleration during isovolumic contraction and systolic velocity at the lateral tricuspid annulus assessed by Doppler tissue imaging did not change. There were weak positive correlations among the Tei index, dP/dt, and systolic pulmonary artery pressure before PTMC (respectively, r= 0.39, r= 0.28, and P= .02, P= .05) but not afterward (respectively, r=0.17, r= 0.02, and P= .20, P= .90). This study suggests that RV dP/dt and Tei index are weakly load dependent, whereas myocardial acceleration during isovolumic contraction is unaffected by acute change in RV afterload.

The Time Constant of Left Ventricular Relaxation

Left ventricular (LV) diastolic dysfunction induces the increase of LV diastolic pressure and subsequently of left atrial and pulmonary capillary pressures independent of systolic function, resulting in the onset of heart failure. In the early 1990s, several clinical studies demonstrated that diastolic dysfunction is an independent prognostic factor in patients with heart failure with reduced ejection fraction (EF).1,2 In the past decade, many clinical studies have clarified that heart failure with preserved EF (HFPEF) accounts for ≈40% of heart failure and that its prognosis is as poor as heart failure with reduced EF.3 With the growing interest in HFPEF, the important role of diastolic dysfunction in the pathogenesis of heart failure has been realized again, because it is plausible that LV diastolic dysfunction is one of the principal causes for this phenotype of heart failure.4 Article see p 268 Major determinants of LV diastolic function are relaxation and stiffness.5 Despite the clinical requisite for their evaluation in understanding the pathophysiology of each patient with heart failure, there are no established indices for the noninvasive assessment of these factors. An invasive measure of LV pressure is required for the evaluation of LV relaxation, and the simultaneous recording of LV pressure and geometry is necessary for the assessment of LV stiffness. LV relaxation abnormality is likely to precede LV stiffening or systolic dysfunction during the development of chronic heart failure and has been assigned as a sensitive sign of LV dysfunction. Peak negative value of the first derivative of LV pressure (peak−dP/dt) has been used as a quantitative index for LV relaxation, but it depends on many other hemodynamic and functional factors. Weiss et al6 showed that the time course of isovolumic pressure decrease subsequent to peak−dP/dt is exponential and proposed the time …

Elemental fractionation in laser ablation-inductively coupled plasma-mass spectrometry: evidence for mass load induced matrix effects in the ICP during ablation of a silicate glass

To study mass load dependent matrix effects in LA-ICP-MS, different masses of aerosols from the NIST 610 glass were generated using a 193 nm ArF excimer laser and a 266 nm Nd:YAG laser and introduced into an ICP-MS. The different mass loads in the ICP were achieved using different crater diameters, the application of an aerosol dilutor, a tandem ablation setup and mixing of a single element matrix (desolvated solution) with the laser generated aerosols. The comparison of results acquired using these different experimental setups supports the existence of a significant matrix effect dependent on the mass load of the ICP. The proof of such effects on 266 nm laser generated aerosols was limited by temporal changes of element ratios due to the generation of a broad particle size distribution and the related incomplete vaporization within the ICP. However, the differences in the particle size distributions measured for various crater diameters as well as the temporal changes of the element ratios using the 193 nm ArF excimer laser were insufficient to explain mass load related changes of the element ratios. It is shown that an increase of the mass load of the ICP by a factor of 16 (crater diameter from 30 to 120 μm) leads to a decrease in certain intensity ratios (e.g., Cu/Ca, Zn/Ca, Cd/Ca, Pb/Ca) up to 25%. Even after taking into account the fact that smaller crater diameters might be partially influenced by laser-induced fractionation, an excessive mass load of the ICP using two 193 nm laser ablation systems demonstrates a further decrease in ion signal intensities of volatile elements in comparison with Ca. In contrast, applying dilution up to a factor of 30 to the aerosols generated using different crater diameters leads to a stabilization of the intensity ratios (e.g. Cd/Ca) to a constant value. The mass load enhanced matrix effect is element dependent and most severe for elements with low melting points (e.g., Cu, Zn, Ag, Cd, Pb). Based on the changes of e.g. As/Ca, Sn/Ca and the constant Be/Ca ratios, an explanation of the plasma induced effects dependent on parameters such as 1st or 2nd ionization potential was impossible. Furthermore, the mass load dependence on easily ionizable elements (Cs, Rb) indicates the absence of incomplete vaporization related effects. In contrast, Al/Ca, Ti/Ca, Th/Ca ratios, for example, remained constant (within 2–3%) with and without dilution. The induction of matrix effects independently of the ablation process by adding various Rb concentrations to the laser aerosols indicates that elements (Cu, Zn, Cd, Pb, U) previously described to be dominantly influenced by laser-induced elemental fractionation undergo significant ICP-induced matrix effects. These matrix effects are mass load dependent and for most elements exceed the contribution of laser-induced fractionation.

Noninvasive Analysis of Myocardial Function Using High-Resolution Doppler Tissue Echocardiography in Rats

The widespread use of rodent models of cardiovascular disease has demanded improved methods of assessing myocardial function. Recently, invasive measurement of cardiac function using conductance catheterization has become available for assessing ventricular performance in small animals. 1-3 However, although pressure-volume loop analysis has become the gold standard, it is impractical for longitudinal assessment of disease or interventions. The ideal method under these circumstances would be noninvasive, an accurate index of contractile function, resistant to the influence of load, and reproducibly measurable in small animals. Doppler tissue echocardiography (DTE) is a new modality that has been widely used to assess cardiac function noninvasively. 4,5 Many indices of systolic function have been described but, as might be expected, ejection-phase indices have been shown to be load dependent. This limits their applicability to the assessment of intrinsic myocardial contractility. We have recently demonstrated that myocardial isovolumic acceleration (IVA), derived by DTE, is a relatively load-independent index of systolic ventricular function that is also capable of describing the force-frequency relationships in both the right ventricle and left ventricle (LV) in porcine models and human beings. 6,7 DTE has previously been used to assess cardiac function in rodent models. For example, myocardial systolic and diastolic velocity gradients were shown to be abnormal in a rat model of myocardial hypertrophy. 8 However, interpretation of such data obtained with conventional probes, which are limited in terms of both spatial and temporal resolution, is difficult. Furthermore, as in studies of larger animals and human beings, interpretation of noninvasively acquired data can only be complete when the load dependency of the index is understood. To our knowledge, there are no systematically obtained data regarding the load dependency of systolic indices of function measured by DTE. This study assesses the use of DTE indices in small rodents. Using a high-resolution probe, we investigated IVA, isovolumic velocity (IVV), and systolic wall velocity (SW) of the LV myocardium together with simultaneous conductance catheter recording of pressure and volume. We examined contractile function to determine the influence of alterations in preload and afterload, and measured the response of these indices to inotropic change.

Effects of progressive myocardial ischaemia on systolic function, diastolic dysfunction, and load dependent relaxation

The aims were to determine (1) the relationship between changes in contractile function (systolic shortening) and the appearance of diastolic dysfunction (postsystolic shortening) during progressive regional left ventricular ischaemia; (2) the effects of increased afterload (acute constriction of the descending thoracic aorta) on ischaemic contractile dysfunction; and (3) the effects of loading during ischaemia on load dependent relaxation. Regional myocardial function, using sonomicrometry, was measured in the short and long axes of the apex of the left ventricle of eight open chest anaesthetised dogs (16-20 kg). Progressive apical ischaemia was induced by graded reductions in left anterior descending coronary artery flow (critical constriction, ischaemia 1, ischaemia 2, total coronary occlusion, and postocclusive maximum reactive hyperaemia). Acute afterloading was induced by a snare placed around the descending aorta. Consistent decreases in systolic shortening and increases in postsystolic shortening relative to the total segmental shortening in the short axis of the apical region were seen with worsening ischaemia. Aortic constriction increased the magnitude of apical postsystolic shortening and decreased apical systolic shortening in the short axis during critical constriction, ischaemia 1, and ischaemia 2. Long axis function changed in a qualitatively similar but quantitatively different manner. There was a significant decrease in the load dependency of relaxation with total coronary occlusion. (1) Changes in systolic and diastolic function occurred concomitantly as mild regional myocardial ischaemia developed and intensified; (2) afterloading significantly worsened regional systolic and diastolic dysfunction during mild ischaemia; and (3) progression of regional ischaemia resulted in loss of load dependent relaxation.

Micro-Mechanical modelling of load dependent friction in contacts of elastic spheres

Recent experimental measurements using twin-axis load cells in storage vessels for bulk solids have revealed load-dependent variation of the wall friction angles measured in the presence of small normal loads on smooth silo walls. The effect is quite appreciable with smooth particles such as plastic beads and glass ballotini, but particles with rough surfaces, like some agricultural seeds, show no such effect.The inclusion of an intrinsic shear resistance at zero normal load into the frictional behaviour (after Briscoe and Tabor) provides a satisfactory prediction of tangential forces required to cause gross sliding of smooth particles over smooth silo walls. This work applies the same adhesive friction concepts to the microdisplacements that occur before full tangential sliding develops.Mindlin analysed the traction profiles for two spheres in contact assuming a constant coefficient of friction, independent of normal stress inside the contact area, with microslip occurring in those portions of the contact area that had a tangential-to-normal stress ratio exceeding the friction coefficient. The assumptions of that analysis preclude the existence of the observed load dependence of wall friction angles. In this paper we re-examine the micromechanical nature of contacts between elastic spheres incorporating tangential stress limits that contain two terms: one proportional to the normal stress at each point in the contact area, the other independent of normal stress. Two possible physical (and mathematical) interpretations of the stress-independent term are discussed, one called adhesive slip and the other stick slip. The resulting traction profiles are examined to determine implications for both microslip and gross-sliding frictional behaviour. A complete theoretical analysis requires the solution of the surface displacement integral over the contact region for a chosen form of the tangential traction profile satisfying appropriate boundary conditions for elastic displacements. Upper and lower bounds and an approximate form for the resulting tangential force-displacement curves are developed and it is shown that such models result in a load-dependent friction behaviour that is very similar to recent experimental wall friction and individual particle friction measurements.