The Association of Age, Sex, and BMI on Lower Limb Neuromuscular and Muscle Mechanical Function in People with Multiple Sclerosis.

(1) Background: The countermovement jump (CMJ) on a force plate could be a sensitive assessment for detecting early lower-limb muscle mechanical deficits in the early stages of multiple sclerosis (MS). CMJ performance is known to be influenced by various anthropometric, physiological, and biomechanical factors, mostly investigated in children and adult athletes. Our aim was to investigate the association of age, sex, and BMI with muscle mechanical function using CMJ to provide a comprehensive overview of lower-limb motor function in people with multiple sclerosis (pwMS). (2) Methods: A cross-sectional study was conducted with pwMS (N = 164) and healthy controls (N = 98). All participants performed three maximal CMJs on a force plate. Age, sex, and BMI were collected from all participants. (3) Results: Significant age, sex, and BMI effects were found for all performance parameters, flight time, and negative and positive power for pwMS and HC, but no significant interaction effects with the group (pwMS, HC) were detected. The highest significant effects were found for sex on flight time (η2 = 0.23), jump height (η2 = 0.23), and positive power (η2 = 0.13). PwMS showed significantly lower CMJ performance compared to HC in middle-aged (31-49 years), with normal weight to overweight and in both women and men. (4) Conclusions: This study showed that age, sex, and BMI are associated with muscle mechanical function in pwMS and HC. These results may be useful in developing reference values for CMJ. This is a crucial step in integrating CMJ into the diagnostic assessment of people with early MS and developing individualized and effective neurorehabilitative therapy.

Patient-specific left atrium contraction quantification associated with atrial fibrillation: A region-based approach.

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) is a widespread cardiac arrhythmia that significantly impacts heart function. AF disrupts atrial mechanical contraction, leading to irregular, uncoordinated, and slow blood flow inside the atria which favors the formation of clots, primarily within the left atrium (LA). A standardized region-based analysis of the LA is missing, and there is not even any consensus about how to define the LA regions. In this study we propose an automatic approach for regionalizing the LA into segments to provide a comprehensive 3D region-based LA contraction assessment. LA global and regional contraction were quantified in control subjects and in AF patients to describe mechanical abnormalities associated with AF. METHODS: The proposed automatic approach for LA regionalization was tested in thirteen control subjects and seventeen AF patients. After dividing LA into standard regions, we evaluated the global and regional mechanical function by measuring LA contraction parameters, such as regional volume, global and regional strains, regional wall motion and regional shortening fraction. RESULTS: LA regionalization was successful in all study subjects. In the AF group compared with control subjects, results showed: a global impairment of LA contraction which appeared more pronounced along radial and circumferential direction; a regional impairment of radial strain which was more pronounced in septal, inferior, and lateral regions suggesting a greater reduction in mechanical efficiency in these regions in comparison to the posterior and anterior ones. CONCLUSION: An automatic approach for LA regionalization was proposed. The regionalization method was proved to be robust with several LA anatomical variations and able to characterize contraction changes associated with AF.

Association between Impaired Renal Function and Subclinical Myocardial Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction: Assessment Using Noninvasive Pressure-Strain Loop.

INTRODUCTION: The objective of this study was to evaluate the abnormal myocardial function in HFpEF patients with renal dysfunction (RD) and investigate the relationship between renal function and myocardial mechanical characteristics in patients with HFpEF. METHODS: 134 patients with HFpEF and 32 control subjects were enrolled in our study. Clinical and echocardiography data were collected for offline analysis. Global work index (GWI), global constructive work (GCW), global waste work (GWW), and global work efficiency (GWE) were measured after noninvasive pressure-strain loop analysis. Univariate and multivariate analyses were used to determine the correlation between renal function and myocardial function in patients with HFpEF. RESULTS: In comparison to control subjects, patients with HFpEF tend to have higher GWW (78 [50-115] vs. 108 [65-160] mm Hg%, p < 0.05) and lower GWE (96 [95-97] vs. 95 [92-96] %, p < 0.05), while left ventricular ejection fraction (65.5 ± 3.3 vs. 64.3 ± 4.6%, p < 0.05) was comparable between them. Besides, increased GWW (86 [58-152] vs. 125 [94-187] mm Hg%, p < 0.05) and decreased GWE (96 [93-97] vs. 94 [92-96] %, p < 0.05) were detected in patients with RD compared to those with normal renal function. An independent correlation was found between estimated glomerular filtration rate and GWW after multivariate analysis. DISCUSSION/CONCLUSION: More severely impaired myocardial function was detected in HFpEF patients with RD compared to those with normal renal function. Estimated glomerular filtration rate was independently correlated to GWW in patients with HFpEF.

Physiological and Physical Strategies to Minimize Damage at the Branch-Stem Junction of Trees: Using the Finite Element Method to Analyze Stress in Four Branch-Stem Features.

This study analyzed the mechanical and physiological strategies associated with four features in the branch-stem junction of a tree, namely the U-shaped branch attachment, the branch collar, the branch bark ridge, and the roughened lower stem. Models were established for each stage of tree growth by adding these four features sequentially to a base model, and the finite element method (FEM) was employed to create three-dimensional models of an Acer tree's branch-stem structure for static force analysis. According to the results, the development of the branch collar shifted the point of breakage to the outer part of the collar and, thus, constituted a physiological strategy that prevented decay in the stem. Additionally, the concentration of stress in the branch bark ridge limited the area of tear in the bark following breakage. Finally, the U-shaped branch attachment reduced stress and shifted the point of peak stress toward the branch, while the thickening of the lower stem reduced the overall stress. The development of these features, including the spatial positioning of the branch bark ridge and branch collar, resulted in two breakage points constituting a physical and a physiological strategy that limited damage to the tree and protected the xylem structure. This is the part that has been challenging to decipher in previous discussions of tree-related self-protection mechanisms.

P-glycoprotein mechanical functional analysis using in silico molecular modeling: Pharmacokinetic variability according to ABCB1 c.2677G > T/A genetic polymorphisms.

P-glycoprotein (P-gp) is a widely membrane-expressed multi-drug transporter. It is unclear whether the pharmacokinetic diversity of P-gp substrates is highly dependent on ABCB1 polymorphisms encoding P-gp. The purpose of this study is to analyze the mechanistic function of P-gp through in silico molecular modeling and to approach the resolution of controversy over pharmacokinetic differences according to ABCB1 polymorphisms. P-gp conformations of apo, ligand-docked, and outward-facing states can be modeled based on structural information of human P-gp. And polymorphic P-gp structures were constructed through homology modeling. ABCB1 c.2677G > T/A (Ala893Ser/Thr), did not correspond to P-gp's nucleotide-binding-domain (NBD) or drug-binding-pocket (DBP) or involve mechanical conformational changes. Although amino acid substitution by ABCB1 c.2677G > T/A caused a 30 % increased strain in an α-helix hinge between the NBD and DBP in P-gp's internal tunnel, there were no overall structural changes compared to wild-type. ABCB1 c.2677G > T/A may increase torsional energy, impacting conformational change rate, but this does not significantly affect P-gp's general functioning. Fexofenadine docking into P-gp's DBP explained the substrate interaction, but no effect by ABCB1 c.2677G > T/A was confirmed. Our findings provide additional insights useful in resolving the debate about the influence of ABCB1 polymorphisms on the interindividual pharmacokinetic variability of P-gp substrates.

The importance of mechanical conditions in the testing of excitation abnormalities in a population of electro-mechanical models of human ventricular cardiomyocytes.

Background: Populations of in silico electrophysiological models of human cardiomyocytes represent natural variability in cell activity and are thoroughly calibrated and validated using experimental data from the human heart. The models have been shown to predict the effects of drugs and their pro-arrhythmic risks. However, excitation and contraction are known to be tightly coupled in the myocardium, with mechanical loads and stretching affecting both mechanics and excitation through mechanisms of mechano-calcium-electrical feedback. However, these couplings are not currently a focus of populations of cell models. Aim: We investigated the role of cardiomyocyte mechanical activity under different mechanical conditions in the generation, calibration, and validation of a population of electro-mechanical models of human cardiomyocytes. Methods: To generate a population, we assumed 11 input parameters of ionic currents and calcium dynamics in our recently developed TP + M model as varying within a wide range. A History matching algorithm was used to generate a non-implausible parameter space by calibrating the action potential and calcium transient biomarkers against experimental data and rejecting models with excitation abnormalities. The population was further calibrated using experimental data on human myocardial force characteristics and mechanical tests involving variations in preload and afterload. Models that passed the mechanical tests were validated with additional experimental data, including the effects of drugs with high or low pro-arrhythmic risk. Results: More than 10% of the models calibrated on electrophysiological data failed mechanical tests and were rejected from the population due to excitation abnormalities at reduced preload or afterload for cell contraction. The final population of accepted models yielded action potential, calcium transient, and force/shortening outputs consistent with experimental data. In agreement with experimental and clinical data, the models demonstrated a high frequency of excitation abnormalities in simulations of Dofetilide action on the ionic currents, in contrast to Verapamil. However, Verapamil showed a high frequency of failed contractions at high concentrations. Conclusion: Our results highlight the importance of considering mechanoelectric coupling in silico cardiomyocyte models. Mechanical tests allow a more thorough assessment of the effects of interventions on cardiac function, including drug testing.

MRI-based measurement of in vivo disc mechanics in a young population due to flexion, extension, and diurnal loading.

Background: Intervertebral disc degeneration is often implicated in low back pain; however, discs with structural degeneration often do not cause pain. It may be that disc mechanics can provide better diagnosis and identification of the pain source. In cadaveric testing, the degenerated disc has altered mechanics, but in vivo, disc mechanics remain unknown. To measure in vivo disc mechanics, noninvasive methods must be developed to apply and measure physiological deformations. Aim: Thus, this study aimed to develop methods to measure disc mechanical function via noninvasive MRI during flexion and extension and after diurnal loading in a young population. This data will serve as baseline disc mechanics to later compare across ages and in patients. Materials & Methods: To accomplish this, subjects were imaged in the morning in a reference supine position, in flexion, in extension, and at the end of the day in a supine position. Disc deformations and vertebral motions were used to quantify disc axial strain, changes in wedge angle, and anterior-posterior (A-P) shear displacement. T2 weighted MRI was also used to evaluate disc degeneration via Pfirrmann grading and T2 time. All measures were then tested for effect of sex and disc level. Results: We found that flexion and extension caused level-dependent strains in the anterior and posterior of the disc, changes in wedge angle, and A-P shear displacements. Flexion had higher magnitude changes overall. Diurnal loading did not cause level-dependent strains but did cause small level-dependent changes in wedge angle and A-P shear displacements. Discussion: Correlations between disc degeneration and mechanics were largest in flexion, likely due to the smaller contribution of the facet joints in this condition. Conclusion: In summary, this study established methods to measure in vivo disc mechanical function via noninvasive MRI and established a baseline in a young population that may be compared to older subjects and clinical disorders in the future.

Zoledronic Acid for prevention of bone and muscle loss after BAriatric Surgery (ZABAS)-a study protocol for a randomized controlled trial.

BACKGROUND: Bariatric surgery has adverse effects on the muscular-skeletal system with loss of bone mass and muscle mass and an increase in the risk of fracture. Zoledronic acid is widely used in osteoporosis and prevents bone loss and fracture. Bisphosphonates may also have positive effects on skeletal muscle. The aim of this study is to investigate the effects of zoledronic acid for the prevention of bone and muscle loss after bariatric surgery.  METHODS/DESIGN: This is a randomized double-blind placebo-controlled study. Sixty women and men with obesity aged 35 years or older will complete baseline assessments before randomization to either zoledronic acid (5 mg in 100 ml isotonic saline) or placebo (100 ml isotonic saline only) 3 weeks before surgery with Roux-en-Y-gastric bypass (RYGB) or sleeve gastrectomy (SG). Follow-up assessments are performed 12 and 24 months after surgery. The primary outcome is changes in lumbar spine volumetric bone mineral density (vBMD) assessed by quantitative computed tomography (QCT). Secondary bone outcomes are changes in proximal femur vBMD assessed by QCT. Changes in cortical and trabecular bone microarchitecture and estimated bone strength will be assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical material bone strength at the mid-tibia diaphysis will be assessed using microindentation and fasting blood samples will be obtained to assess biochemical markers of bone turnover and calcium metabolism.  Secondary muscle outcomes include whole body lean mass assessed using dual-energy X-ray absorptiometry. Dynamometers will be used to assess handgrip, shoulder, ankle, and knee muscle strength. Short Physical Performance Battery, 7.6-m walking tests, 2-min walking test, and a stair climb test will be assessed as biomarkers of physical function. Self-reported physical activity level is assessed using International Physical Activity Questionnaire (IPAQ). DISCUSSION: Results from this study will be instrumental for the evidence-based care of patients undergoing bariatric surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04742010. Registered on 5 February 2021.

Cardiac cycle timing and contractility following acute sport-related concussion.

Cardiac sequelae following sport-related concussion are not well understood. This study describes changes in the cardiac cycle timing intervals and contractility parameters during the acute phase of concussion. Twelve athletes (21 ± 2 years, height = 182 ± 9 cm, mass = 86 ± 15 kg, BMI = 26 ± 3 kg/m2) were assessed within 5 days of sustaining a diagnosed concussion against their own pre-season baseline. A non-invasive cardiac sensor (LLA RecordisTM) was used to record the cardiac cycle parameters of the heart for 1 minute during supine rest. Cardiac cycle timing intervals (Isovolumic relaxation and contraction time, Mitral valve open to E wave, Rapid ejection period, Atrial systole to mitral valve closure, Systole, and Diastole) and contractile forces (Twist force and Atrial systole: AS) were compared. Systolic time significantly decreased during acute concussion (p = 0.034). Magnitude of AS significantly increased during acute concussion (p = 0.013). These results imply that concussion can result in altered systolic function.

Electromechanical reciprocity and arrhythmogenesis in long-QT syndrome and beyond.

An abundance of literature describes physiological and pathological determinants of cardiac performance, building on the principles of excitation-contraction coupling. However, the mutual influencing of excitation-contraction and mechano-electrical feedback in the beating heart, here designated 'electromechanical reciprocity', remains poorly recognized clinically, despite the awareness that external and cardiac-internal mechanical stimuli can trigger electrical responses and arrhythmia. This review focuses on electromechanical reciprocity in the long-QT syndrome (LQTS), historically considered a purely electrical disease, but now appreciated as paradigmatic for the understanding of mechano-electrical contributions to arrhythmogenesis in this and other cardiac conditions. Electromechanical dispersion in LQTS is characterized by heterogeneously prolonged ventricular repolarization, besides altered contraction duration and relaxation. Mechanical alterations may deviate from what would be expected from global and regional repolarization abnormalities. Pathological repolarization prolongation outlasts mechanical systole in patients with LQTS, yielding a negative electromechanical window (EMW), which is most pronounced in symptomatic patients. The electromechanical window is a superior and independent arrhythmia-risk predictor compared with the heart rate-corrected QT. A negative EMW implies that the ventricle is deformed-by volume loading during the rapid filling phase-when repolarization is still ongoing. This creates a 'sensitized' electromechanical substrate, in which inadvertent electrical or mechanical stimuli such as local after-depolarizations, after-contractions, or dyssynchrony can trigger abnormal impulses. Increased sympathetic-nerve activity and pause-dependent potentiation further exaggerate electromechanical heterogeneities, promoting arrhythmogenesis. Unraveling electromechanical reciprocity advances the understanding of arrhythmia formation in various conditions. Real-time image integration of cardiac electrophysiology and mechanics offers new opportunities to address challenges in arrhythmia management.

The Syndesmosis Procedure Correction of Hallux Valgus Feet Associated With the Metatarsus Adductus Deformity.

Metatarsus adductus and hallux valgus are common foot deformities. Corrective surgery of hallux valgus feet with metatarsus adductus deformity can be challenging and experience a high deformity recurrence rate. The purpose of this study was to demonstrate if the syndesmosis procedure can correct such feet satisfactorily without osteotomies and arthrodesis. 75 hallux valgus feet in 45 patients with a Sgarlato's metatarsal adductus angle ≥15° were studied after having undergone the syndesmosis procedure for an average of 20.22 months. Their average preoperative intermetatarsal angle of 12.56° was improved to 6.00° (p < .001) and metatarsophalangeal angle from 35.61° to 23.46° (p < .001) significantly. Their average American Orthopedic Foot and Ankle Society's clinical scores improved significantly from 56.41 to 90.53 points (p < .001). Fifty-five feet (73.33%) had preoperative metatarsal calluses, and all but 3 had a noticeable reduction in severity. Forty-one patients (91.11%) were able to return to their desired activities and footwear. All relevant raw data formed this study, including x-ray and photographic images, were submitted as Supplementary Material for online viewing and reference. Despite the possible intrinsic rigidity of metatarsus adductus forefoot, this study demonstrated that hallux valgus feet with metatarsus adductus deformity could be corrected anatomically and functionally with the soft tissue syndesmosis procedure and without correcting the preexisting metatarsus adductus deformity. This study also supports the notion that the MA deformity accentuates hallux valgus alignment preoperatively and postoperatively, and possibly all feet in general.

Titin (TTN): from molecule to modifications, mechanics, and medical significance.

The giant sarcomere protein titin is a major determinant of cardiomyocyte stiffness and contributor to cardiac strain sensing. Titin-based forces are highly regulated in health and disease, which aids in the regulation of myocardial function, including cardiac filling and output. Due to the enormous size, complexity, and malleability of the titin molecule, titin properties are also vulnerable to dysregulation, as observed in various cardiac disorders. This review provides an overview of how cardiac titin properties can be changed at a molecular level, including the role isoform diversity and post-translational modifications (acetylation, oxidation, and phosphorylation) play in regulating myocardial stiffness and contractility. We then consider how this regulation becomes unbalanced in heart disease, with an emphasis on changes in titin stiffness and protein quality control. In this context, new insights into the key pathomechanisms of human cardiomyopathy due to a truncation in the titin gene (TTN) are discussed. Along the way, we touch on the potential for titin to be therapeutically targeted to treat acquired or inherited cardiac conditions, such as HFpEF or TTN-truncation cardiomyopathy.

Left atrial appendage orifice area and morphology is closely associated with flow velocity in patients with nonvalvular atrial fibrillation.

BACKGROUND: Thromboembolic events are the most serious complication of atrial fibrillation (AF), and the left atrial appendage (LAA) is the most important site of thrombosis in patients with AF. During the period of COVID-19, a non-invasive left atrial appendage detection method is particularly important in order to reduce the exposure of the virus. This study used CT three-dimensional reconstruction methods to explore the relationship between LAA morphology, LAA orifice area and its mechanical function in patients with non-valvular atrial fibrillation (NVAF). METHODS: A total of 81 consecutive patients with NVAF (36 cases of paroxysmal atrial fibrillation and 45 cases of persistent atrial fibrillation) who were planned to undergo catheter radiofrequency ablation were enrolled. All patients were examined by transthoracic echocardiography (TTE), TEE, and computed tomography angiography (CTA) before surgery. The LAA orifice area was obtained according to the images of CTA. According to the left atrial appendage morphology, it was divided into chicken wing type and non-chicken wing type. At the same time, TEE was performed to determine left atrial appendage flow velocity (LAAFV), and the relationship between the left atrial appendage orifice area and LAAFV was analyzed. RESULTS: The LAAFV in Non-chicken wing group was lower than that in Chicken wing group (36.2 ± 15.0 cm/s vs. 49.1 ± 22.0 cm/s, p-value < 0.05). In the subgroup analysis, the LAAFV in Non-chicken wing group was lower than that in Chicken wing group in the paroxysmal AF (44.0 ± 14.3 cm/s vs. 60.2 ± 22.8 cm/s, p-value < 0.05). In the persistent AF, similar results were observed (29.7 ± 12.4 cm/s vs. 40.8 ± 17.7 cm/s, p-value < 0.05). The LAAFV in persistent AF group was lower than that in paroxysmal AF group (34.6 ± 15.8 cm/s vs. 49.9 ± 20.0 cm/s, p-value < 0.001). The LAAFV was negatively correlated with left atrial dimension (R = - 0.451, p-value < 0.001), LAA orifice area (R= - 0.438, p-value < 0.001) and left ventricular mass index (LVMI) (R= - 0.624, p-value < 0.001), while it was positively correlated with LVEF (R = 0.271, p-value = 0.014). Multiple linear regression analysis showed that LAA morphology (ß = - 0.335, p-value < 0.001), LAA orifice area (ß = - 0.185, p-value = 0.033), AF type (ß = - 0.167, p-value = 0.043) and LVMI (ß = - 0.465, p-value < 0.001) were independent factors of LAAFV. CONCLUSIONS: The LAA orifice area is closely related to the mechanical function of the LAA in patients with NVAF. The larger LAA orifice area and LVMI, Non-chicken wing LAA and persistent AF are independent predictors of decreased mechanical function of LAA, and these parameters might be helpful for better management of LA thrombosis.

FEV1 is independently related with impaired left atrial strain in chronic obstructive pulmonary disease patients: A speckle tracking study.

BACKGROUND: Atrial fibrillation (AF) is common in chronic obstructive pulmonary disease (COPD) patients. It is known that impaired forced expiratory volume in 1 s (FEV1) is one of the risk factors of cardiovascular disease. Two-dimensional speckle tracking echocardiography (2D-STE) can detect deterioration of left atrial mechanical functions in the subclinical stage. We hypothesized that reduced lung functions, measured by FEV1 in COPD patients, may be associated with impaired left atrial (LA) mechanical functions. OBJECTIVES: Present study included 127 consecutive COPD patients. We divided study population into two groups: patients with normal LA strain (n = 20) or with impaired LA strain (n = 107). RESULTS: In univariate logistic regression analysis, age (p: 0.001), FEV1% (p < 0.001), FEV1 (p < 0.001), FEV1/forced vital capacity (FVC) (p: 0.014), white blood cell (p: 0.012), LA Max vol (p: 0.026), C-reactive protein (p :0.001), arterial oxygen pressure (PaO2 ) (p: 0.019), arterial oxygen saturation (SO2 ) (p: 0.021), left ventricle ejection fraction (LVEF) (p: 0.042), and mitral A-wave velocity (p: 0.017) were associated with impaired LA-strain. In multivariate logistic regression analysis, age (p: 0.043), FEV1 (p < 0.001), LA Max vol (p: 0.004), and LVEF (p: 0.004) were independently associated with impaired LA strain. CONCLUSION: FEV1 is associated with impaired left atrial strain independently of arterial blood gas and left ventricular diastolic dysfunction parameters in COPD patients with preserved left ventricular systolic function.

Contemporary narrative review on left atrial strain mechanics in echocardiography: cardiomyopathy, valvular heart disease and beyond.

Left atrial (LA) strain mechanics refer to the measurement of LA myocardial deformation expressed as a percentage, and have been gathering interest over the last decade with expanding research supporting their utility in multiple cardiovascular disorders. Measured through advanced dynamic imaging techniques which include tissue Doppler imaging (TDI) and two-dimensional (2D) speckle tracking echocardiography (STE), LA strain mechanics are affected by left ventricular diastolic dysfunction prior to the onset of functional and structural changes in the left ventricle (LV). There is a need for practising cardiologists to become more familiar with the clinical utility of LA strain mechanics. In this article, we begin by reviewing the physiologic function of the LA, using this as a basis for understanding LA strain mechanics. The focus of this review article is to provide a contemporary update on the utility of LA strain mechanics in a range of cardiovascular disorders, including atrial fibrillation (AF), hypertrophic cardiomyopathy (HCM), valvular pathologies, coronary artery disease (CAD) as well as systemic diseases, such as hypertension (HTN), obesity and diabetes mellitus (DM). This article also highlights the current limitations in more widespread clinical applications of LA strain mechanics, as well as outlining the future perspectives on the clinical applications of LA strain mechanics.

Paradoxical association between lipoprotein cholesterol levels and left atrial function in hypertensive diabetic patients: A speckle tracking study.

BACKGROUND: Studies have shown that subclinical left atrial (LA) dysfunction can be diagnosed with two-dimensional speckle tracking echocardiography (2D-STE). Although low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular diseases, recent studies have reported a paradoxical relationship between LDL-C level and atrial fibrillation. In this study, we investigated the relationship between LDL-C levels and LA function. METHODS: In 168 patients with the diagnosis of hypertension and diabetes, transthoracic echocardiography with LA 2D-STE was performed. The patients were then divided into two groups: normal LA-strain (n = 94) or impaired LA-strain (n = 74). The relationship between LDL-C and LA function was analyzed. RESULTS: Patients with impaired LA-strain had higher body mass index (BMI) (p = 0.029), higher statin usage (p = 0.003), and lower LDL-C levels (p = 0.001) than patients with normal LA-strain. They also had lower left ventricle ejection fraction (LVEF) (p = 0.047) and higher E-wave velocity (mitral e, m/s) (p = 0.020). Multivariate logistic regression analysis showed that lower LDL-C (p = 0.034), higher BMI (p = 0.004), lower LVEF (p = 0.004), and higher E-wave velocity (p = 0.003) values were independently associated with impaired LA-strain. The area under the receiver operating curve of LDL-C in predicting impaired LA-strain was 0.645 (0.564-0.730, p < 0.05). LDL-C ≤ 112.5 mg/dl was found to be the optimal cut-off value with 74.5% sensitivity and 51.2% specificity in predicting impaired LA strain. CONCLUSION: In patients with hypertension and diabetes, LDC-C levels are moderately but independently and paradoxically associated with impaired LA function assessed by 2D-STE.

Tissue Expression of Atrial and Ventricular Myosin Light Chains in the Mechanism of Adaptation to Oxidative Stress.

Ischemia/reperfusion (I/R) injury induces post-translational modifications of myosin light chains (MLCs), increasing their susceptibility to degradation by matrix metalloproteinase 2 (MMP-2). This results in the degradation of ventricular light chains (VLC1) in heart ventricles. The aim of the study was to investigate changes in MLCs content in the mechanism of adaptation to oxidative stress during I/R. Rat hearts, perfused using the Langendorff method, were subjected to I/R. The control group was maintained in oxygen conditions. Lactate dehydrogenase (LDH) activity and reactive oxygen/nitrogen species (ROS/RNS) content were measured in coronary effluents. Atrial light chains (ALC1) and ventricular light chains (VLC1) gene expression were examined using RQ-PCR. ALC1 and VLC1 protein content were measured using ELISA tests. MMP-2 activity was assessed by zymography. LDH activity as well as ROS/RNS content in coronary effluents was higher in the I/R group (p = 0.01, p = 0.04, respectively), confirming heart injury due to increased oxidative stress. MMP-2 activity in heart homogenates was also higher in the I/R group (p = 0.04). ALC1 gene expression and protein synthesis were significantly increased in I/R ventricles (p < 0.01, 0.04, respectively). VLC1 content in coronary effluents was increased in the I/R group (p = 0.02), confirming the increased degradation of VLC1 by MMP-2 and probably an adaptive production of ALC1 during I/R. This mechanism of adaptation to oxidative stress led to improved heart mechanical function.

Long-Term Effects With Potential Clinical Importance of Botulinum Toxin Type-A on Mechanics of Muscles Exposed.

Botulinum toxin type-A (BTX-A) is widely used for spasticity management and mechanically aims at reducing passive resistance at the joint and widening joint range of movement. However, recent experiments on acute BTX-A effects showed that the injected rat tibialis anterior (TA) muscle's passive forces increased, and the length range of active force exertion (l range) did not change. Additionally, BTX-A was shown to spread into non-injected muscles in the compartment and affect their mechanics. Whether those effects persist in the long term is highly important, but unknown. The aim was to test the following hypotheses with experiments conducted in the anterior crural compartment of the rat: In the long term, BTX-A (1) maintains l range, (2) increases passive forces of the injected TA muscle, and (3) spreads into non-injected extensor digitorum longus (EDL) and the extensor hallucis longus (EHL) muscles, also affecting their active and passive forces. Male Wistar rats were divided into two groups: BTX-A and Control (0.1 units of BTX-A or only saline was injected into the TA). Isometric forces of the muscles were measured simultaneously 1-month post-injection. The targeted TA was lengthened, whereas the non-targeted EDL and EHL were kept at constant length. Hydroxyproline analysis was done to quantify changes in the collagen content of studied muscles. Two-way ANOVA test (for muscle forces, factors: TA length and animal group) and unpaired t or Mann-Whitney U test (for l range and collagen content, where appropriate) were used for statistical analyses (P < 0.05). BTX-A caused significant effects. TA: active forces decreased (maximally by 75.2% at short and minimally by 48.3%, at long muscle lengths), l range decreased (by 22.9%), passive forces increased (by 12.3%), and collagen content increased (approximately threefold). EDL and EHL: active forces decreased (up to 66.8%), passive force increased (minimally by 62.5%), and collagen content increased (approximately twofold). Therefore, hypothesis 1 was rejected and 2 and 3 were confirmed indicating that previously reported acute BTX-A effects persist and advance in the long term. A narrower l range and an elevated passive resistance of the targeted muscle are unintended mechanical effects, whereas spread of BTX-A into other compartmental muscles indicates the presence of uncontrolled mechanical effects.

Patellofemoral Mechanics: a Review of Pathomechanics and Research Approaches.

PURPOSE OF REVIEW: The patellofemoral joint is a complicated articulation of the patella and femur that is prone to pathologies. The purpose of this review is to report on the current methods of investigating patellofemoral mechanics, factors that affect joint function, and future directions in patellofemoral joint research with emerging technologies and techniques. RECENT FINDINGS: While previous hypotheses have suggested that the patella is only a moment arm extender, recent literature has suggested that the patella influences the control of knee moments and forces acting on the tibia as well as contributes to various aspects of patellar function with minimal neural input. With advancements in simulating a six-degrees-of-freedom patellofemoral joint, we have gained a better understanding of patella motion and have shown that geometry and muscle activations impact patella mechanics. Research into influences on patella mechanics from other joints such as the hip and foot has become more prevalent. In this review, we report current in vivo, in vitro, and in silico approaches to studying the patellofemoral joint. Kinematic and anatomical factors that affect patellofemoral joint function such as patella alta and tilt or bone morphology and ligaments are discussed. Moving forward, we suggest that advanced in vivo dynamic imaging methods coupled to musculoskeletal simulation will provide further understanding of patellofemoral pathomechanics and allow engineers and clinicians to design interventions to mitigate or prevent patellofemoral pathologies.

Ex vivo Methods for Measuring Cardiac Muscle Mechanical Properties.

Cardiovascular disease continues to be the leading cause of morbidity and mortality in the United States and thousands of manuscripts each year are aimed at elucidating mechanisms underlying cardiac disease. The methods for quantifying cardiac performance are quite varied, with each technique assessing unique features of cardiac muscle mechanical properties. Accordingly, in this review, we discuss current ex vivo methods for quantifying cardiac muscle performance, highlighting what can be learned from each method, and how each technique can be used in conjunction to complement others for a more comprehensive understanding of cardiac function. Importantly, cardiac function can be assessed at several different levels, from the whole organ down to individual protein-protein interactions. Here, we take a reductionist view of methods that are commonly used to measure the distinct aspects of cardiac mechanical function, beginning with whole heart preparations and finishing with the in vitro motility assay. While each of the techniques are individually well-documented in the literature, there is a significant need for a comparison of the techniques, delineating the mechanical parameters that can are best measured with each technique, as well as the strengths and weaknesses inherent to each method. Additionally, we will consider complementary techniques and how these methods can be used in combination to improve our understanding of cardiac mechanical function. By presenting each of these methods, with their strengths and limitations, in a single manuscript, this review will assist cardiovascular biologists in understanding the existing literature on cardiac mechanical function, as well as designing future experiments.