FITTING OF HYPERELASTIC CONSTITUTIVE MODELS IN DIFFERENT SHEEP HEART REGIONS BASED ON BIAXIAL MECHANICAL PROPERTIES

Heart failure remains one of the leading causes of death especially among people over the age of 60 years worldwide. To develop effective therapy and suitable replacement materials for the heart muscle it is necessary to understand its biomechanical behaviour under load. This paper investigates the passive mechanical response of the sheep myocardia excised from three different regions of the heart. Due to the relatively higher cost and huge ethical demands in acquisition and testing of real animal heart models, this paper evaluates the fitting performances of five different constitutive models on the myocardial tissue responses. Ten sheep were sacrificed, and their hearts excised and transported within 3h to the testing biomechanical laboratory. The upper sections of the hearts above the short axes were carefully dissected out. Tissues were dissected from the mid-sections of the left ventricle, mid-wall and right ventricle for each heart. The epicardia and endocardia were then carefully sliced off each tissue to leave the myocardia. Stress-strain curves were calculated, filtered and resampled. The results show that Choi-Vito model was found to provide the best fit to the LV, the polynomial (Anisotropic) model to RV, the Four-Fiber Family model to RV, Holzapfel (2000) to RV, Holzapfel (2005) to RV and the Fung model to LV.

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785 Causes of death on heart failure

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(06)80536-9 ◽

2006 ◽

Vol 5 (1) ◽

pp. 188-189

Author(s):

M ANASTASIU ◽

C MIHAI ◽

C CALTEA ◽

C SINESCU

Keyword(s):

Heart Failure ◽

Causes Of Death

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Aetiology-dependent impairment of mitochondrial function in the failing human heart

European Heart Journal ◽

10.1093/ehjci/ehaa946.3606 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J Borger ◽

D Scheiber ◽

P Horn ◽

D Pesta ◽

U Boeken ◽

...

Keyword(s):

Heart Failure ◽

Mitochondrial Function ◽

Human Study ◽

Left Ventricular ◽

Myocardial Tissue ◽

Funding Source ◽

Ros Production ◽

German Research Foundation ◽

Long Term Outcome ◽

Tissue Specimens

Abstract Background Alterations of mitochondrial function have been identified to play a role in Heart Failure (HF) pathophysiology. Oxidative phosphorylation (OXPHOS) capacity of the myocardium was shown to be reduced in the failing heart. Ineffective mitochondrial function promotes formation of reactive oxygen species (ROS) that may affect remodelling in ischemia. Thus far, human mitochondrial function comparing dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) resembling the main aetiologies of heart failure with reduced ejection fraction (HFrEF) has not been investigated. Purpose We hypothesised that 1. ROS production is elevated in left ventricular myocardial tissue specimens of ICM patients compared to DCM. 2. Mitochondrial OXPHOS capacity is higher in left ventricular myocardial tissue specimens of DCM compared to ICM patients. Methods Myocardial tissue was obtained from the left ventricular apex from 63 patients (38 ICM, 25 DCM) with advanced HFrEF requiring implantation of a Left Ventricular Assist Device (LVAD). We performed high-resolution respirometry (HRR, OROBOROS Oxygraph-2k) in saponine-permeabilised myocardial fibres and measured ROS production fluoroscopically via the Amplex Red method. Statistical analysis was conducted using GraphPad Prism 7 and IBM SPSS v26.0. Results Groups were of comparable age (61.5±1.2 vs. 59.3±2.4 years, p=n.s.), sex (87% vs 85% male, p=n.s.), diabetic status (32% vs 38.4% type 2 diabetes mellitus, p=n.s.), and body mass index (28.1±0.8 vs. 26.3±1.1 kg/m2, p=n.s.). We detected reduced myocardial mitochondrial OXPHOS capacity in ICM under state 3 conditions by about 15% (68.7±34.0 vs. 80.9±30.5 pmol/(s*mg), p<0.05), after addition of Glutamate by 25% (78.9±38.7 vs. 104.8±41.2 pmol/(s*mg), p<0.01) as well as after Succinate (115.5±65.5 vs. 155±62.0 pmol/(s*mg), p<0.01), uncoupling agent FCCP (114.1±56.8 vs. 150.5±47.3 pmol/(s*mg), p<0.01), and by about 40% after addition of Complex I inhibitor Rotenone (55.5±25.9 vs. 96.9±28.0 pmol/(s*mg), p<0.001). We detected no difference in ROS production between ICM and DCM (0.6±0.05 vs. 0.76±0.08 pmol/(s*ml), p=n.s.). Conclusion This is the first human study deciphering distinct alterations in mitochondrial function (OXPHOS capacity) in ventricular myocardium of HFrEF patients. Future studies may address how distinct metabolic patterns at the time of implantation may relate to long-term outcome of HFrEF in terms of remodelling and recovery. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): DFG (German Research Foundation)

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Ability of Constitutive Models to Characterize the Temperature Dependence of Rubber Hyperelasticity and to Predict the Stress-Strain Behavior of Filled Rubber under Different Defor Mation States

Polymers ◽

10.3390/polym13030369 ◽

2021 ◽

Vol 13 (3) ◽

pp. 369

Author(s):

Xintao Fu ◽

Zepeng Wang ◽

Lianxiang Ma

Keyword(s):

Experimental Data ◽

Temperature Dependence ◽

Mechanical Response ◽

Constitutive Models ◽

Uniaxial Tensile ◽

Uniaxial Tensile Test ◽

Chain Model ◽

Stress Strain ◽

Filled Rubber ◽

Yeoh Model

In this paper, some representative hyperelastic constitutive models of rubber materials were reviewed from the perspectives of molecular chain network statistical mechanics and continuum mechanics. Based on the advantages of existing models, an improved constitutive model was developed, and the stress–strain relationship was derived. Uniaxial tensile tests were performed on two types of filled tire compounds at different temperatures. The physical phenomena related to rubber deformation were analyzed, and the temperature dependence of the mechanical behavior of filled rubber in a larger deformation range (150% strain) was revealed from multiple angles. Based on the experimental data, the ability of several models to describe the stress–strain mechanical response of carbon black filled compound was studied, and the application limitations of some constitutive models were revealed. Combined with the experimental data, the ability of Yeoh model, Ogden model (n = 3), and improved eight-chain model to characterize the temperature dependence was studied, and the laws of temperature dependence of their parameters were revealed. By fitting the uniaxial tensile test data and comparing it with the Yeoh model, the improved eight-chain model was proved to have a better ability to predict the hyperelastic behavior of rubber materials under different deformation states. Finally, the improved eight-chain model was successfully applied to finite element analysis (FEA) and compared with the experimental data. It was found that the improved eight-chain model can accurately describe the stress–strain characteristics of filled rubber.

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QSYQ Attenuates Oxidative Stress and Apoptosis Induced Heart Remodeling Rats through Different Subtypes of NADPH-Oxidase

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/824960 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Yong Wang ◽

Chun Li ◽

Yuli Ouyang ◽

Tianjiao Shi ◽

Xiaomin Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Nadph Oxidase ◽

Caspase 3 ◽

Ventricular Remodeling ◽

Cardiac Injury ◽

Myocardial Tissue ◽

Therapeutic Effects ◽

Histological Changes ◽

Nadph Oxidase 4

We aim to investigate the therapeutic effects of QSYQ, a drug of heart failure (HF) in clinical practice in China, on a rat heart failure (HF) model. 3 groups were divided: HF model group (LAD ligation), QSYQ group (LAD ligation and treated with QSYQ), and sham-operated group. After 4 weeks, rats were sacrificed for cardiac injury measurements. Rats with HF showed obvious histological changes including necrosis and inflammation foci, elevated ventricular remodeling markers levels(matrix metalloproteinases-2, MMP-2), deregulated ejection fraction (EF) value, increased formation of oxidative stress (Malondialdehyde, MDA), and up-regulated levels of apoptotic cells (caspase-3, p53 and tunnel) in myocardial tissue. Treatment of QSYQ improved cardiac remodeling through counter-acting those events. The improvement of QSYQ was accompanied with a restoration of NADPH oxidase 4 (NOX4) and NADPH oxidase 2 (NOX2) pathways in different patterns. Administration of QSYQ could attenuate LAD-induced HF, and AngII-NOX2-ROS-MMPs pathway seemed to be the critical potential targets for QSYQ to reduce the remodeling. Moreover, NOX4 was another key targets to inhibit the p53 and Caspase3, thus to reduce the hypertrophy and apoptosis, and eventually provide a synergetic cardiac protective effect.

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Uncertainty Quantification in Predicting Behaviour of Rubber-Like Materials in Uni-Axial Loading

Volume 12: Mechanics of Solids, Structures, and Fluids ◽

10.1115/imece2020-24200 ◽

2020 ◽

Author(s):

Aref Ghaderi ◽

Vahid Morovati ◽

Pouyan Nasiri ◽

Roozbeh Dargazany

Keyword(s):

Uncertainty Quantification ◽

Mechanical Response ◽

Pure Shear ◽

Constitutive Models ◽

Material Behavior ◽

Elastic Behavior ◽

Deterministic Models ◽

Data Set ◽

Material Parameters ◽

Axial Extension

Abstract Material parameters related to deterministic models can have different values due to variation of experiments outcome. From a mathematical point of view, probabilistic modeling can improve this problem. It means that material parameters of constitutive models can be characterized as random variables with a probability distribution. To this end, we propose a constitutive models of rubber-like materials based on uncertainty quantification (UQ) approach. UQ reduces uncertainties in both computational and real-world applications. Constitutive models in elastomers play a crucial role in both science and industry due to their unique hyper-elastic behavior under different loading conditions (uni-axial extension, biaxial, or pure shear). Here our goal is to model the uncertainty in constitutive models of elastomers, and accordingly, identify sensitive parameters that we highly contribute to model uncertainty and error. Modern UQ models can be implemented to use the physics of the problem compared to black-box machine learning approaches that uses data only. In this research, we propagate uncertainty through the model, characterize sensitivity of material behavior to show the importance of each parameter for uncertainty reduction. To this end, we utilized Bayesian rules to develop a model considering uncertainty in the mechanical response of elastomers. As an important assumption, we believe that our measurements are around the model prediction, but it is contaminated by Gaussian noise. We can make the noise by maximizing the posterior. The uni-axial extension experimental data set is used to calibrate the model and propagate uncertainty in this research.

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Abstract 17097: Non-Synonymous Mitochondrial DNA Variants Are Common in Myocardial Tissue of Heart Failure Patients

Circulation ◽

10.1161/circ.142.suppl_3.17097 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Pappu Ananya ◽

Michael Binder ◽

Yang Wanjun ◽

Rebecca McClellan ◽

Brittney Murray ◽

...

Keyword(s):

Heart Failure ◽

Mitochondrial Dna ◽

Nuclear Dna ◽

Left Ventricular ◽

Individual Risk ◽

Myocardial Tissue ◽

Mtdna Mutation ◽

Mtdna Mutations ◽

Ventricular Tissue ◽

Mtdna Variants

Introduction: Mitochondrial heart disease due to pathogenic mitochondrial DNA (mtDNA) mutations can present as hypertrophic or dilated cardiomyopathy, ventricular arrhythmias and conduction disease. It is estimated that the mutation rate of mtDNA is 10 to 20-fold higher than that of nuclear DNA genes due to damage from reactive oxygen species released as byproducts during oxidative phosphorylation. When a new mtDNA mutation arises, it creates an intracellular heteroplasmic mixture of mutant and normal mtDNAs, called heteroplasmy. Heteroplasmy levels can vary in various tissues and examining mtDNA variants in blood may not be representative for the heart. The frequency of pathogenic mtDNA variants in myocardial tissues in unknown. Hypothesis: Human ventricular tissue may contain mtDNA mutations which can lead to alterations in mitochondrial function and increase individual risk for heart failure. Methods: Mitochondrial DNA was isolated from 61 left ventricular myocardial samples obtained from failing human hearts at the time of transplantation. mtDNA was sequenced with 23 primer pairs. In silico prediction of non-conservative missense variants was performed via PolyPhen-2. Heteroplasmy levels of variants predicted to be pathogenic were quantified using allele-specific ARMS-PCR. Results: We identified 21 mtDNA non-synonymous variants predicted to be pathogenic in 17 hearts. Notably, one heart contained four pathogenic mtDNA variants (ATP6: p.M104; ND5: p.P265S; ND4: p.N390S and p.L445F). Heteroplasmy levels exceeded 90% for all four variants in myocardial tissue and were significantly lower in blood. No pathogenic mtDNA variants were identified in 44 hearts. Hearts with mtDNA mutations had higher levels of myocardial GDF-15 (growth differentiation factor-15; 6.2±2.3 vs. 1.3±0.18, p=0.045), an established serum biomarker in various mitochondrial diseases. Conclusions: Non-synonymous mtDNA variants predicted to be pathogenic are common in human left ventricular tissue and may be an important modifier of the heart failure phenotype. Future studies are necessary to correlate myocardial mtDNA mutations with cardiovascular outcomes and to assess whether serum GDF-15 allows identifying patients with myocardial mtDNA mutations.

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Abstract 5853: Continuous Flow Left Ventricular Assist Device in Women with Advanced Heart Failure: Results After One Year of Support

Circulation ◽

10.1161/circ.118.suppl_18.s_1016 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Salpy V Pamboukian ◽

Roberta C Bogaev ◽

Stuart D Russell ◽

Andrew J Boyle ◽

Nader Moazami ◽

...

Keyword(s):

Heart Failure ◽

Continuous Flow ◽

Cardiac Transplantation ◽

Causes Of Death ◽

Left Ventricular ◽

Advanced Heart Failure ◽

Ventricular Assist Devices ◽

Ventricular Assist ◽

Left Ventricular Assist ◽

One Year

Small continuous flow left ventricular assist devices (LVAD) are providing new options for women in advanced heart failure who due to body size limitations were historically excluded from use of large first generation pulsatile devices. We report the experience of women one year after implantation with the new, HeartMate II continuous flow LVAD for bridge to transplantation. Patients (n=279), 24% female (F), 76% male (M) in NYHA Class IV heart failure, LV ejection fraction 16±7% (F), 16±6% (M), mostly inotrope dependent and about half on intraaortic balloon pump support (50% F, 43% M), who had been enrolled in the HM II clinical trial for at least 1 year as a bridge to cardiac transplantation at 33 centers were analyzed. Outcomes and causes of death in the first year of support between F and M recipients were determined. The percentage of patients who had undergone transplantation, recovery of the heart with device removal, or continued on HM II support after one year were the same (80%) between M and F. However, the percentage of patients who had received a heart transplant was significantly less for F (38%) than M (53%) (p<0.05). Median duration of support for F was 226 days (range 8–1004) vs. 143 days (range 0–1057) for M. Mortality on device support was 20% for F and 18% M. There were no statistically significant differences in leading causes of death: sepsis (1.5% F vs 4.2% M), ischemic stroke (3.1% F vs 1.9% M), hemorrhagic stroke (3.1% F vs 1.4% M), and right heart failure (3.1% F vs 1.9% M). Of 82 patients continuing on support at 1 year, 26 (32%) were F with median BSA of 1.65 vs 2.14 m 2 for M. Kaplan Meier survival at one year was similar for females (74%) and males (76%). The smaller, more durable HM II rotary LVAD may be especially advantageous to women with advanced HF as a bridge to cardiac transplantation, because of significantly smaller BSA and need for extended duration of mechanical support due to longer wait times for suitable organ donors. Outcomes at one-year

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Caesarean Section in Eclampsia and its Outcome in Bangladesh

KYAMC Journal ◽

10.3329/kyamcj.v6i1.32787 ◽

2017 ◽

Vol 6 (1) ◽

pp. 583-586

Author(s):

MA Mazid ◽

Shahida Akter

Keyword(s):

Heart Failure ◽

Pulmonary Embolism ◽

Caesarean Section ◽

Conservative Management ◽

Causes Of Death ◽

Post Partum ◽

Economic Status ◽

Treatment Options ◽

Age Difference ◽

Significant Difference

This prospective study was carried out on a total number of 58 eclamptic subjects during the period of July 2010 to June 2012 where 38 were undergone caesarean section (LUCS - Lower Uterine Caesarean Section) and 20 received conservative management. Mean (±SD) Age of the subjects who undergone Caesarean Section and conservative management (NVD) were 23.67±8.63 and 23.45±9.31 years respectively. Significant mean age difference was also present between these two groups. In 38 subjects of LUCS 34 subjects were recovered and rest 4 cases were died. Possible causes of death were due to heart failure and post partum pulmonary embolism. Among these 20 subjects who were treated conservatively 14 were recovered and 6 subjects were died. Causes of death in these groups were pulmonary embolism, Septic pneumonia, and HELLP syndrome. Significant difference was found between these two treatment options. It was observed that socio-demographic, economic status and BMI had significant effects on management outcome.KYAMC Journal Vol. 6, No.-1, Jul 2015, Page 583-586

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Reynoutrin Improves Ischemic Heart Failure in Rats Via Targeting S100A1

Frontiers in Pharmacology ◽

10.3389/fphar.2021.703962 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wenkai Yang ◽

Hanjian Tu ◽

Kai Tang ◽

Haozhong Huang ◽

Shi Ou ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Cardiac Function ◽

Protein Expression ◽

Myocardial Fibrosis ◽

Ischemic Heart ◽

Inflammatory Factors ◽

Myocardial Tissue ◽

Ischemic Heart Failure ◽

Tgf Β1

This study investigated the effects of reynoutrin on the improvement of ischemic heart failure (IHF) and its possible mechanism in rats. The rat heart failure model was established by permanently ligating the left anterior descending coronary artery (LAD) and administering different doses of reynoutrin. Cardiac function, inflammatory factors releasing, oxidative stress, cardiomyocytes apoptosis, and myocardial fibrosis were evaluated. Western blotting was used to determine protein expression levels of S100 calcium-binding protein A1 (S100A1), matrix metallopeptidase 2(MMP2), MMP9, phosphorylated (p-) p65, and transforming growth factor -β1 (TGF-β1) in myocardial tissue of the left ventricle. Results showed that reynoutrin significantly improved cardiac function, suppressed the release of inflammatory factors, reduced oxidative stress, inhibited cardiomyocytes apoptosis, and attenuated myocardial fibrosis in rats with IHF. In rat myocardial tissue, permanent LAD-ligation resulted in a significant down-regulation in S100A1 expression, whereas reynoutrin significantly up-regulated S100A1 protein expression while down-regulating MMP2, MMP9, p-p65, and TGF-β1 expressions. However, when S100A1 was knocked down in myocardial tissue, the above-mentioned positive effects of reynoutrin were significantly reversed. Reynoutrin is a potential natural drug for the treatment of IHF, and its mechanism of action involves the up-regulation of S100A1 expression, thereby inhibiting expressions of MMPs and the transcriptional activity of nuclear factor kappa-B.

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Abstract 16981: Proteomic Profiles of Diabetic Heart Failure Report on Myocardial Metabolism, Ventricular Hypertrophy, and Endothelial Dysfunction

Circulation ◽

10.1161/circ.142.suppl_3.16981 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Lauren K Truby ◽

Lydia Kwee ◽

Jessica A Regan ◽

Dawn E Bowles ◽

Carmelo A Milano ◽

...

Keyword(s):

Heart Failure ◽

Endothelial Dysfunction ◽

Ventricular Hypertrophy ◽

Factor H ◽

Energy Utilization ◽

Myocardial Tissue ◽

Complement Factor ◽

Proteomic Profiling ◽

Biochemical Basis ◽

Intracellular Energy

Introduction: There is a complex epidemiologic relationship between type two diabetes mellitus (DM) and heart failure (HF), and it is unclear whether the biochemical basis of HF differs in patients with and without DM. Hypothesis: Proteomic profiling of myocardial tissue from patients with and without DM will identify unique signatures of diabetic HF. Methods: Using the Olink aptamer-based platform, we performed proteomic profiling of 552 proteins on 37 myocardial tissue samples: 9 controls, 10 with HF, 7 with DM, and 11 with HF+DM. One-way ANOVA was first used to identify proteins that differed across the four groups. Associated proteins were then tested for differences between HF+DM and each other group independently; we retained proteins with the same direction of effect for each comparison. Each analysis was controlled for false discovery rate (q<0.1). Results: We identified 12 proteins that differed significantly between HF+DM and all three other groups. Among these, six proteins were significant after FDR adjusted ANOVA and had the same direction of effect. These included 5’-NT (q=5.35E-07), a regulator of intracellular energy utilization, and carboxypeptidase A2, a metalloprotease that cleaves peptides during digestion (q=0.0003). Expression of myocardial leptin receptors (q=0.001), complement factor H related protein (q=0.003), and carbonic anhydrase (q=0.006) were also upregulated in diabetic HF, and have previously been linked to myocyte hypertrophy. Markers of endothelial dysfunction - ESM-1 (q=5.62E-06) and VEGFR-3 (q=0.024) - were also increased in HF+DM myocardium as compared to other groups (Figure 1). Conclusions: Proteomic profiling of HF, DM, and HF+DM myocardial tissue suggest alterations in intracellular energy substrate utilization as well as increased expression of tissue biomarkers previously associated with ventricular hypertrophy and myocardial remodeling.

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