• 대한의용생체공학회:의공학회지
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• 제5권1호
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• pp.33-38
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• 1984

Biological rhythms are very important phenomena to generate, grow a living thing. However, the origin of rhythms are not disclosed completely until now. Eack myocardial cell has a natural rhythm of itself, and synchronization is happened when two cells are come in contact with each other. In this research, a simple synchronization model has been proposed and studied, refering to the physiological model. The changes of the synchronization rhythms in experimental results are compared with that of the model.

• Biomolecules & Therapeutics
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• 제26권2호
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• pp.121-129
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• 2018

Oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and apoptosis play critical roles in the pathogenesis of atherosclerosis. Thioredoxin-1 (Trx) is an antioxidant that potently protects various cells from oxidative stress-induced cell death. However, the protective effect of Trx on ox-LDL-induced macrophage foam cell formation and apoptosis has not been studied. This study aims to investigate the effect of recombinant human Trx (rhTrx) on ox-LDL-stimulated RAW264.7 macrophages and elucidate the possible mechanisms. RhTrx significantly inhibited ox-LDL-induced cholesterol accumulation and apoptosis in RAW264.7 macrophages. RhTrx also suppressed the ox-LDL-induced overproduction of lectin-like oxidized LDL receptor (LOX-1), Bax and activated caspase-3, but it increased the expression of Bcl-2. In addition, rhTrx markedly inhibited the ox-LDL-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). Furthermore, anisomycin (a p38 MAPK activator) abolished the protective effect of rhTrx on ox-LDL-stimulated RAW264.7 cells, and SB203580 (a p38 MAPK inhibitor) exerted a similar effect as rhTrx. Collectively, these findings indicate that rhTrx suppresses ox-LDL-stimulated foam cell formation and macrophage apoptosis by inhibiting ROS generation, p38 MAPK activation and LOX-1 expression. Therefore, we propose that rhTrx has therapeutic potential in the prevention and treatment of atherosclerosis.

• 대한의용생체공학회:의공학회지
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• 제15권4호
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• pp.407-412
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• 1994

This paper describes the construction of an anisotropic three dimensional ventricular model based on the bidomain model. The cardiac activation process in the normal cardiac cell and the myocardial ischemic cell are simulated by the Huygen's principle. The depolarization process in the myocardial ischemia displays the delayed activation compared to the normal state. The repolarization process is simulated by the myocardial potential at the arbitrary ellapsed time after activation process. Using the potential data, the equivalent cardiac source at the arbitrary time can be computed. In conclusion, this simulation suggests the possibilities of the depolarization and the repolarization process in the normal and abnormal myocardiac cells.

• 대한의용생체공학회:학술대회논문집
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• 대한의용생체공학회 1995년도 춘계학술대회
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• pp.82-86
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• 1995

Using electrocardiography is a common method to diagnose heart disease, Modeling and simulation of activation process for the heart system is useful to understand electrocardiography. This paper proposes a two-dimensional cellular automata model for the activation process of the ventricles. The model represents the geometry of the ventricles by the ellipsoidal shape in two dimension. In the model, ventricles are divided into four layers, each of which has a set of cells with preassigned properties. The proposed model takes Into account the local orientation of the myocardial fibers and their distributed velocity, and refractory period. Simulation experiment is performed to measure activation potential for each cell in each layer within the ventricles.

• 동의생리병리학회지
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• 제17권4호
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• pp.952-957
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• 2003

To certify the protective effect of herbal medicine against oxygen free radical-induced myocardiotoxicity, cytotoxicity was measured using LDH activity and TBARS assay in the presence of Jisilhaebaekgyejitang(JHGT) extracts or single constituents of this prescription, In the present study, xanthine oxidase/hypoxanthine (XO/HX) resulted in a cell damage such as increases in LDH activity in culture medium and lipid peroxidation in cultured myocardial cells. In the effect of JHGT extract and its single constituents, which are Fructus Ponciri Seu Aurantii Immaturus (FPSAI), Cortex Magnoliae Officinalis (CMO), Bulbus Allii Macrostemi (BAM), Ramulus Cinnamomi (RC) and Fructus Trichosanthis (FT), they showed the prevention from the XO/HX-induced cardiotoxicity by the decrease of LDH activity and lipid peroxidation. From these results, they show that XO/HX is cardiotoxic in cultured myocardial cells derived from neonatal rat, and it suggests that JHGT, FPSAI, PT, CMO, BAM, RC and FT extracts are positively effective in the blocking in XO/HX-induced cardiotoxicity.

• The Korean Journal of Physiology and Pharmacology
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• 제18권1호
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• pp.67-72
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• 2014

To investigate the alteration of c-Jun N-terminal kinase (JNK) activity after myocardial ischemia reperfusion injury (MIRI) and further explore the effect of naloxone postconditioning on MIRI. Forty male Sprague Dawley rats were randomly divided into five groups: sham operation (sham, n=8); ischemia reperfusion (IR, n=8); IR+naloxone 0.5 mg/kg (Nal L, n=8); IR+naloxone 1.0 mg/kg (Nal M, n=8); IR+naloxone 2.0 mg/kg (Nal H, n=8). Pathological changes of myocardial tissue were visualized by HE staining. The expression of p-JNK, and the apoptosis of cardiomyocytes were investigated with Western blotting and the TUNEL assay, respectively. Irregular arrangement and aberrant structure of myocardial fibers, cardiomyocytes with granular or vacuolar degeneration, and inflammatory cells infiltrating the myocardial interstitial regions characterized MIRI in the IR group. Signs of myocardial injury and inflammatory infiltration were less prominent in the Nal-treated groups. The expression of p-JNK in the sham group and in all Nal-treated groups was significantly lower than that in the IR group (p<0.01). The apoptosis index of cardiomyocytes in the IR group was significantly higher than in the sham group (p<0.01). The apoptosis indices of cardiomyocytes in all Nal-treated groups were significantly reduced to 55.4%, 26.2%, and 27.6%, respectively, of the IR group (p<0.01). This study revealed that Naloxone postconditioning before reperfusion inhibits p-JNK expression and decreases cell apoptosis, thus alleviating MIRI.

• Preventive Nutrition and Food Science
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• 제17권3호
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• pp.177-183
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• 2012

Interruption of blood flow through coronary arteries and its subsequent restoration triggers the generation of a burst of reactive oxygen species (ROS), leading to myocardial cell death. In this study, we determined whether a methanol extract of Cassia mimosoides var. nomame Makino could prevent myocardial ischemia-reperfusion injury. When radical scavenging activity of the extract was measured in vitro using its ${\alpha}$,${\alpha}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH) radical quenching ability, the extract showed an activity slightly lower than that of ascorbic acid. Three days after oral administration of the extract (400 mg/kg/day) to rats, myocardial ischemia/reperfusion injury was generated by 30 min of ligation of the left anterior descending coronary artery (LAD), followed by 3 hr reperfusion. Compared with the vehicle-treated group, administration of the extract significantly reduced infarct size (IS) (ratio of infarct area to area at risk) in the extract-treated group by 28.3%. Reduction in the cellular injury was mediated by attenuation of Bax/Bcl-2 ratio by 33.3%, inhibition of caspase-3 activation from procaspase-3 by 40%, and subsequent reduction in the number of apoptotic cells by 66.3%. These results suggest that the extract attenuates myocardial injury in a rat model of ischemia-reperfusion by scavenging ROS, including free radicals, and consequently blocking apoptotic cascades. Therefore, intake of Cassia mimosoides var. nomame Makino might be beneficial for preventing ischemic myocardial injury.

• Journal of Chest Surgery
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• 제18권4호
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• pp.759-770
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• 1985

This study was experimentally undertaken to evaluate the effect of hypothermic oxygenated cardioplegic solution on myocardial protection during prolonged aortic cross clamping under cardiopulmonary bypass. Dogs were divided into two groups control group [received hypothermic unoxygenated cardioplegic solution] and experimental group [received hypothermic oxygenated cardioplegic solution]. Coronary sinus effluent was obtained at once and 30, 60, 90 minutes after cross-clamping for the determination of pH, PCO2,PO2 and lactate level during the infusion of cardioplegic solution and myocardial biopsies were obtained after cessation of 90 minutes of aortic cross-clamping. The results obtained were as follows: 1. There was no significant differences in the pH and PCO2 between the oxygenated and unoxygenated cardioplegic solution but the PO2 of the oxygenated solution was 4 times greater than unoxygenated solution, and also the oxygenated solution had a significantly greater oxygen content [2.020.05 ml 02/min] and had much more oxygen delivery than unoxygenated solution. 2. The myocardial oxygen consumption and the myocardial oxygen extraction in oxygenated group were 1.63 ml 02/100 ml and 67.32% respectively, which was greater than those in unoxygenated group. 3. Regarding to pH and PCO2 of coronary sinus effluent, there was no significant differences between two groups in early period of infusion of cardioplegic solution, but the pH shifted to acidosis from 60 minutes, PCO2 increased from 90 minutes of aortic cross-clamping, and PO2 markedly decreased from 90 minutes of aortic cross-clamping in unoxygenated group. 4. The lactate concentration of coronary sinus effluent revealed relatively normal in both groups, but showed slight increase up to 27.54.56 mg/100 ml at 90 minutes of aortic cross-clamping in unoxygenated group. 5. On electron microscopic study, the ultrastructural integrity of myocardial cells in oxygenated group was well preserved within 90 minutes. Slight swelling and deformity of mitochondria, interfibrillar widening, and disarrangement of myofibrils were observed at 90 minutes after aortic cross-clamping in unoxygenated group. From these results, the use of hypothermic oxygenated cardioplegic solution seemed to be effective and better method for the preservation of ischemic myocardium during the prolonged aortic cross-clamping.

• Journal of Veterinary Science
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• 제22권4호
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• pp.54.1-54.13
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• 2021

Background: Hypoxia causes oxidative stress and affects cardiovascular function and the programming of cardiovascular disease. Melatonin promotes antioxidant enzymes such as superoxide dismutase, glutathione reductase, glutathione peroxidase, and catalase. Objectives: This study aims to investigate the correlation between melatonin and hypoxia induction in cardiomyocytes differentiation. Methods: Mouse embryonic stem cells (mESCs) were induced to myocardial differentiation. To demonstrate the influence of melatonin under hypoxia, mESC was pretreated with melatonin and then cultured in hypoxic condition. The cardiac beating ratio of the mESC-derived cardiomyocytes, mRNA and protein expression levels were investigated. Results: Under hypoxic condition, the mRNA expression of cardiac-lineage markers (Brachyury, Tbx20, and cTn1) and melatonin receptor (Mtnr1a) was reduced. The mRNA expression of cTn1 and the beating ratio of mESCs increased when melatonin was treated simultaneously with hypoxia, compared to when only exposed to hypoxia. Hypoxia-inducible factor (HIF)-1α protein decreased with melatonin treatment under hypoxia, and Mtnr1a mRNA expression increased. When the cells were exposed to hypoxia with melatonin treatment, the protein expressions of phospho-extracellular signal-related kinase (p-ERK) and Bcl-2-associated X proteins (Bax) decreased, however, the levels of phospho-protein kinase B (p-Akt), phosphatidylinositol 3-kinase (PI3K), B-cell lymphoma 2 (Bcl-2) proteins, and antioxidant enzymes including Cu/Zn-SOD, Mn-SOD, and catalase were increased. Competitive melatonin receptor antagonist luzindole blocked the melatonin-induced effects. Conclusions: This study demonstrates that hypoxia inhibits cardiomyocytes differentiation and melatonin partially mitigates the adverse effect of hypoxia in myocardial differentiation by regulating apoptosis and oxidative stress through the p-AKT and PI3K pathway.

• IMMUNE NETWORK
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• 제22권6호
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• pp.49.1-49.15
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• 2022

Exosomes derived from mesenchymal stem cells (MSCs) could protect against myocardial infarction (MI). TLR4 is reported to play an important role in MI, while microRNA-182-5p (miR-182-5p) negatively regulates TLR4 expression. Therefore, we hypothesize that MSCs-derived exosomes overexpressing miR-182-5p may have beneficial effects on MI. We generated bone marrow mesenchymal stem cells (BM-MSCs) and overexpressed miR-182-5p in these cells for exosome isolation. H₂O₂-stimulated neonatal mouse ventricle myocytes (NMVMs) and MI mouse model were employed, which were subjected to exosome treatment. The expression of inflammatory factors, heart function, and TLR4 signaling pathway activation were monitored. It was found that miR-182-5p decreased TLR4 expression in BM-MSCs and NMVMs. Administration of exosomes overexpressing miR-182-5p to H₂O₂-stimulated NMVMs enhanced cell viability and suppressed the expression of inflammatory cytokines. In addition, they promoted heart function, suppressed inflammatory responses, and de-activated TLR4/NF-κB signaling pathway in MI mice. In conclusion, miR-182-5p transferred by the exosomes derived from BM-MSCs protected against MI-induced impairments by targeting TLR4.