Injectable Hydrogels for Cardiac Tissue Engineering

In light of the limited efficacy of current treatments for cardiac regeneration, tissue engineering approaches have been explored for their potential to provide mechanical support to injured cardiac tissues, deliver cardio‐protective molecules, and improve cell‐based therapeutic techniques. Injectable hydrogels are a particularly appealing system as they hold promise as a minimally invasive therapeutic approach. Moreover, injectable acellular alginate‐based hydrogels have been tested clinically in patients with myocardial infarction (MI) and show preservation of the left ventricular (LV) indices and left ventricular ejection fraction (LVEF). This review provides an overview of recent developments that have occurred in the design and engineering of various injectable hydrogel systems for cardiac tissue engineering efforts, including a comparison of natural versus synthetic systems with emphasis on the ideal characteristics for biomimetic cardiac materials.     

6th International Conference on Flow Analysis

Abstract

The 2.5th order differential polarographic reduction behavior of malonaldehyde (MLD) was studied. A sensitive measurement method of the determination of MLD for biological samples was given by using differential voltammetry with a static mercury drop electrode at a scanning speed of 80mV/s in a solution of 0.1mol/L NH₄Cl. The linear response range of current(e″) against the concentration of MLD was 1.0×10^?6 to 1.0×10^?3 mol L and the detection limit was 1.0 × 10^?7mol/L. The contents of MLD in the sample of cardiac myocytes was determined rapidly and simply by means of the method.     

Effect of phalloidin on filaments polymerized from heart muscle ADP-actin monomers

The effect of phalloidin on filaments polymerized from ADP-actin monomers of the heart muscle was investigated with differential scanning calorimetry. Heart muscle contains α-skeletal and α-cardiac actin isoforms. In the absence of phalloidin the melting temperature was 55°C for the α-cardiac actin isoform and 58°C for the α-skeletal one when the filaments were generated from ADP-actin monomers. After the binding of phalloidin the melting temperature was isoform independent (85.5°C). We concluded that phalloidin stabilized the actin filaments of α-skeletal and α-cardiac actin isoforms to the same extent when they were polymerized from ADP-actin monomers.     

A Novel Cardiac Glycoside from Parepigynum funingesis

From the dried aerial part ofParepigynumfuningesis Tsiang et P. T. Li (Apocynaceae),a new cardiac glucoside, named parefuningoside (1) had been isolated. Its structure was determined by means of hydrolysis and spectral analysis.     

Nanomaterials‐based Electrochemical Sensing of Cardiac Biomarkers for Acute Myocardial Infarction: Recent Progress

The development of the methods for early and accurate diagnosis of acute myocardial infarction are needed to facilitate immediate treatment of patients. One of the ways to achieve that is the detection of cardiac biomarkers for myocardial infarction, such as thrombin, cardiac troponins (I and T), myoglobin, etc. Nanotechnology has played an important role in the development of sensitive and efficient electrochemical sensors for cardiac biomarkers. In this review, we discuss recent progress on nanomaterial‐based electrochemical sensing of various cardiac biomarkers for acute myocardial infarction.     

用表面等离子体子共振传感器测定人心肌肌钙蛋白I的研究

采用自组装表面等离子体子共振(SPR)传感装置,固定入射角,以波长为变量,以CCD为检测系统,用对金和抗体均有较强吸附作用的葡萄球菌A蛋白作为基底膜,观测了人心肌肌钙蛋白I的抗体和抗原之间免疫反应的动力学过程,并进行了人心肌肌钙蛋白I的定量测定.结果表明,人心肌肌钙蛋白I的浓度在5.0～50μg/L范围内与传感器的响应值呈线性关系.     

心脏外科手术后脑梗死患者的影像学特点及相关因素分析

本文对心脏外科手术后脑梗死患者的影像学特点及发生脑梗死的相关因素进行探讨。选取本院心脏外科手术患者286例作为研究对象,术后34例发生脑梗死,按照手术方式的不同将脑梗死患者分为体外循环组(11例)和非体外循环组(23例),比较两组术后脑梗死的影像学特点,并对心脏外科手术后脑梗死的影响因素进行分析。研究发现,两组穿支梗死、分水岭梗死、多发梗死、陈旧梗死的发生率比较,差异无统计学意义(P>0.05);体外循环组皮层梗死的发生率明显低于非体外循环组,体外循环组大面积梗死、双侧梗死的发生率明显高于非体外循环组,差异有统计学意义(P<0.05)。经单因素分析,性别、空腹血糖、TC、TG、LDL-C、Hcy、吸烟、饮酒不是心脏外科手术后脑梗死的影响因素(P>0.05),年龄、文化程度、高血压病史、糖尿病为心脏外科手术后脑梗死的影响因素(P<0.05),经多因素二元Logistic回归分析,年龄高、文化程度低、高血压病史≥10、有糖尿病,是心脏外科手术后脑梗死的独立影响因素(P<0.05)。结果显示,体外循环手术常为大面积梗死、双侧梗死,症状较重,而非体外循环手术常为皮层梗死,且两者分水岭梗死较多,均与栓塞和低灌注有关。心脏外科手术后脑梗死与年龄高、文化程度低、高血压病史≥10、有糖尿病密切相关,早期给予针对性预防干预可能降低脑梗死的发生。     

从富宁藤中得到的两类新的强心苷以及它们之间的可能的生源转化途径

Five novel cardiac glycosides with two types of unusual aglycone [funingenin A (2a) and B], named funingenosides E-I (2-6), together with a known compound, funingenoside B (1), were isolated from the aerial part of Parepigynumfuningense Tsiang et P. T. Li (Apocynaceae). The structures of 2-6 were elucidated by means of MS, IR, NMR spectral analyses and chemical degradation. The possible biogenetic pathway of the two types of cardiac glycosides was also discussed.     

Internal flexibility of cardiac myosins

Conventional and saturation transfer electron paramagnetic resonance spectroscopy (EPR and ST EPR) and differential scanning calorimetry (DSC) were used to study the motional dynamics and segmental flexibility of cardiac myosins.Cardiac myosins isolated from bovine and human heart muscle were spin-labelled with isothiocyanate- or maleimide-based probe molecules at the reactive sulfhydryl sites (Cys-697 and Cys-707) of the motor domain. The maleimide probe molecules attached to human cardiac myosin rotated with an effective rotational correlation time of 33 ns which was at least eight times shorter than the rotational correlation time of the same label on skeletal myosin (260 ns). In the presence of MgADP and MgADP plus orthovanadate, flexibility changes in the multisubunit structure of myosins were detected, but this did not lead to changes of the overall rotational property of the myosin heads. Significant difference in the internal flexibility was detected on myosin samples isolated from ischemic tissue, the rotational correlation time decreased to 25 ns.DSC measurements supported the view that addition of nucleotides produced additional loosening in the multisubunit structure of cardiac myosin. It is postulated that there is an intersite communication between the nucleotide binding domain and the 20 kDa subunit where the reactive thiol sites are located.This work was supported by grants from the National Research Foundation (OTKA T 017099) and Ministry of Social Welfare (ETT 737/1993). The Bruker ESP 300 E spectrometer and the SETARAM Micro DSC-II used in the experiments were purchased with funds provided by the National Research Foundation Grants CO-123 and CO-272. The computer (PC-386) was supported by POPEX Ltd., Pécs, Hungary. The authors thank to Prof. Dr. K. Hideg (Central Research Laboratory) for providing the iodoacetamide spin label.     

Assessment of Platelet Reactivity and Inflammatory Markers in Coronary Artery Bypass Graft Patients Treated with Acetylsalicylic Acid with Flavonoid Supplementation

The recommended pharmacological therapy for patients with coronary artery disease (CAD) treated by coronary artery bypass grafting (CABG) is acetylsalicylic acid (ASA). To improve the antiplatelet effect, supplementation with flavonoids is also recommended. The aim of this study was to estimate anti-aggregation properties of diosmin, in combination with ASA, pre- and postoperatively and assess the relationship of this therapy with inflammatory processes in CAD patients undergoing CABG. The study patients (n = 26) took diosmin (1000 mg/day); the control patients (n = 27) took a placebo. The therapeutic period for taking diosmin was from at least 30 days before to 30 days after CABG. All patients also took 75 mg/day ASA. Platelet aggregation and IL-6, CRP, and fibrinogen concentrations were determined before and 30 days after surgery. Results showed that diosmin did not enhance the anti-aggregation effect of ASA at any assessment time. However, there was a stronger anti-aggregation effect 30 days after surgery that was diosmin independent and was associated with acute-phase markers in the postoperative period. Increased levels of inflammatory markers in the late phase of the postoperative period may provide an unfavorable prognostic factor in long-term follow-up, which should prompt the use of stronger antiplatelet therapy in patients after CABG.     

N-Acetyl Cysteine,Selenium, and Ascorbic Acid Rescue Diabetic Cardiac Hypertrophy via Mitochondrial-Associated Redox Regulators

Metabolic disorders often lead to cardiac complications. Metabolic deregulations during diabetic conditions are linked to mitochondrial dysfunctions, which are the key contributing factors in cardiac hypertrophy. However, the underlying mechanisms involved in diabetes-induced cardiac hypertrophy are poorly understood. In the current study, we initially established a diabetic rat model by alloxan-administration, which was validated by peripheral glucose measurement. Diabetic rats displayed myocardial stiffness and fibrosis, changes in heart weight/body weight, heart weight/tibia length ratios, and enhanced size of myocytes, which altogether demonstrated the establishment of diabetic cardiac hypertrophy (DCH). Furthermore, we examined the expression of genes associated with mitochondrial signaling impairment. Our data show that the expression of PGC-1α, cytochrome c, MFN-2, and Drp-1 was deregulated. Mitochondrial-signaling impairment was further validated by redox-system dysregulation, which showed a significant increase in ROS and thiobarbituric acid reactive substances, both in serum and heart tissue, whereas the superoxide dismutase, catalase, and glutathione levels were decreased. Additionally, the expression levels of pro-apoptotic gene PUMA and stress marker GATA-4 genes were elevated, whereas ARC, PPARα, and Bcl-2 expression levels were decreased in the heart tissues of diabetic rats. Importantly, these alloxan-induced impairments were rescued by N-acetyl cysteine, ascorbic acid, and selenium treatment. This was demonstrated by the amelioration of myocardial stiffness, fibrosis, mitochondrial gene expression, lipid profile, restoration of myocyte size, reduced oxidative stress, and the activation of enzymes associated with antioxidant activities. Altogether, these data indicate that the improvement of mitochondrial dysfunction by protective agents such as N-acetyl cysteine, selenium, and ascorbic acid could rescue diabetes-associated cardiac complications, including DCH.     

Antiepileptic Drug Tiagabine Does Not Directly Target Key Cardiac Ion Channels Kv11.1, Nav1.5 and Cav1.2

Tiagabine is an antiepileptic drug used for the treatment of partial seizures in humans. Recently, this drug has been found useful in several non-epileptic conditions, including anxiety, chronic pain and sleep disorders. Since tachycardia—an impairment of cardiac rhythm due to cardiac ion channel dysfunction—is one of the most commonly reported non-neurological adverse effects of this drug, in the present paper we have undertaken pharmacological and numerical studies to assess a potential cardiovascular risk associated with the use of tiagabine. A chemical interaction of tiagabine with a model of human voltage-gated ion channels (VGICs) is described using the molecular docking method. The obtained in silico results imply that the adverse effects reported so far in the clinical cardiological of tiagabine could not be directly attributed to its interactions with VGICs. This is also confirmed by the results from the isolated organ studies (i.e., calcium entry blocking properties test) and in vivo (electrocardiogram study) assays of the present research. It was found that tachycardia and other tiagabine-induced cardiac complications are not due to a direct effect of this drug on ventricular depolarization and repolarization.     

Label‐free Electrochemical Immunosensor for Cardiac Troponin T Based on Exfoliated Graphite Nanoplatelets Decorated with Gold Nanoparticles

This paper describes the application of exfoliated graphite nanoplatelets (xGnP) decorated with gold nanoparticles (AuNP) for the development of a label‐free electrochemical immunosensor for the determination of human cardiac troponin T (TnT), an important cardiac biomarker in the diagnosis of acute myocardial infarction (AMI). Heparin‐stabilized AuNP (AuNP‐Hep) were synthesized, characterized and supported on xGnP. The material obtained (AuNP‐Hep‐xGnP) was used as a platform to immobilize the anti‐TnT by adsorption and this was then applied in the construction of an immunosensor. Under optimized conditions, using differential pulse voltammetry (DPV) and an incubation time of 20 min, the proposed immunosensor showed linearity in the range of 0.050 to 0.35 ng mL⁻¹ TnT, with a calculated limit of detection of 0.016 ng mL⁻¹. The interday precision (n=7) showed a coefficient of variation of 6.5 %. Some potential interferents commonly present in blood plasma samples were investigated and the degree of interference was found to be low (less than 10 %), demonstrating adequate selectivity for analytical applications. The biosensor was successfully applied in the determination of TnT in fortified samples of human blood plasma.     

Modulation of material properties of a decellularized myocardial matrix scaffold

Injectable materials offer the potential for minimally invasive therapy for myocardial infarction (MI), either as an acellular scaffold or as a cell delivery vehicle. A recently developed myocardial matrix hydrogel, derived from decellularized porcine ventricular tissue, has the potential to aid in cardiac repair following an MI. Herein, we set out to study the effects of cross-linking on the cardiac hydrogel stiffness, degradation properties, cellular migration, and catheter injectability in vitro. Cross-linking increased stiffness, while slowing degradation and cellular migration through the gels. Additionally, the cross-linked material was pushed through a clinically relevant catheter. These results demonstrate that the material properties of myocardial matrix can be tuned via cross-linking, while maintaining appropriate viscosity for catheter injectability.     

NMR-Based Metabolomic Analysis of Cardiac Tissues Clarifies Molecular Mechanisms of CVB3-Induced Viral Myocarditis and Dilated Cardiomyopathy

Viral myocarditis (VMC), which is defined as inflammation of the myocardium with consequent myocardial injury, may develop chronic disease eventually leading to dilated cardiomyopathy (DCM). Molecular mechanisms underlying the progression from acute VMC (aVMC), to chronic VMC (cVMC) and finally to DCM, are still unclear. Here, we established mouse models of VMC and DCM with Coxsackievirus B3 infection and conducted NMR-based metabolomic analysis of aqueous metabolites extracted from cardiac tissues of three histologically classified groups including aVMC, cVMC and DCM. We showed that these three pathological groups were metabolically distinct from their normal counterparts and identified three impaired metabolic pathways shared by these pathological groups relative to normal controls, including nicotinate and nicotinamide metabolism; alanine, aspartate and glutamate metabolism; and D-glutamine and D-glutamate metabolism. We also identified two extra impaired metabolic pathways in the aVMC group, including glycine, serine and threonine metabolism; and taurine and hypotaurine metabolism Furthermore, we identified potential cardiac biomarkers for metabolically distinguishing these three pathological stages from normal controls. Our results indicate that the metabolomic analysis of cardiac tissues can provide valuable insights into the molecular mechanisms underlying the progression from acute VMC to DCM.     

Thermodynamic characterization of different actin isoforms

Summary The thermodynamic properties of the cardiac and skeletal a-actin isoforms were studied to characterize the molecular bases of the functional differences between them with the method of differential scanning calorimetry (DSC). The thermal properties of the actin filaments were described in the presence of calcium and magnesium ions as well. Based on the calculated free energy changes the α-cardiac actin filaments appeared to be more stable in its physiologically more relevant, magnesium saturated form. The magnesium saturated form of the α-cardiac actin filaments seemed to be more stable compared to the calcium saturated form of it. The enthalpy and entropy changes could differentiate between the α-cardiac and α-skeletal actin isoforms and between the calcium and magnesium saturated cardiac actin isoforms as well. Our results can demonstrate that the few differences between the amino acid sequences of the α-actin isoforms have an influence on the thermal properties and maybe on the function of these proteins as well.