• Proceeding of EDISON Challenge
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• 2017.03a
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• pp.625-627
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• 2017

Cardiovascular disease is the leading cause of death in America [1]. This kind of situation leads researcher to find out how to analyze the disease without using a living human heart. Computer simulation is the solution. Based on the existed clinical data and mathematical formulas from the journals, we can simulate a human heart activity using a computer. Moreover, we can also use the existed biological data in our simulation program, such as CellML (Cell Markup Language) [2].

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.79-87
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• 1982

Higenamine(dl-demethylcoclaurine, dl-1-(4-hydroxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrah-ydroisoquinoline hydrochloride), which has recently been isolated from Aconite root by Drs. Kosuge and Yokota, has known to be the main cardiotonic component of the Aconite root. The present study was undertaken to investigate the effects of Higenamine on the calcium binding and release and ATPase activity of fragmented cardiac sarcoplasmic reticulum under in vitro condition. The calcium binding and release of sarcoplasmic reticulum were measured by using the double-beam spectrophotometer and the calcium sensitive dye, murexide. In the presence of $10^{-4}{\sim}5{\times}10^{-3}M$ of Higenamine, the maximal calcium binding and the initial binding rate of porcine cardiac sarcoplasmic reticulum were inhibited dose dependently by up to 43%. However, the calcium release from cardiac sarcoplasmic reticulum, which was loaded with $Ca^{++}(50{\mu}M)$, was stimulated in dose dependent manner. When incubated in the medium of 20 mM Tris-maleate(pH 7.0), 100 mM KCl, 10 mM $MgCl_2,\;0.05mM\;CaCl_2\;and\;0.014{\sim}1\;mM\;Tris-ATP\;at\;30^{\circ}C$ in the presence of Higenamine $(10^{-4}{\sim}5{\times}10^{-3}M)$, both $Ca^{++}-and\;Mg^{++}-ATPase$ of sarcoplasmic reticulum were inhibited non-competitively by Higenamine and values of $K_i$ were 4.896 mM and 6.875 mM respectively. It is suggested from the above findings that the cardiotonic effects of Higenamine might be partially explained by the inhibition of calcium binding and the stimulation of calcium release from the sarcoplasimic reticulum which may increase the free intracellular calcium that is available in the contraction of the cardiac muscle fiber.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.515-523
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• 2000

Polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia/reperfusion (MI/R) injury. Moreover, platelets are also important blood cells that can aggravate myocardial ischemic injury. This study was designed to test the effects of PMNs and platelets separately and together in provoking cardiac dysfunction in isolated perfused rat hearts following ischemia and reperfusion. Additional control rat hearts were perfused with $75{\times}10^6$ PMNs, with $75{\times}10^6$ platelets, or with $75{\times}10^6\;PMNs+75{\times}10^6$ platelets over a five minute perfusion followed by a 75 min observation period. No significant reduction in coronary flow (CF), left ventricular developed pressure (LVDP), or the first derivative of LVDP (dP/dt max) was observed at the end of the observation period in any non-ischemic group. Similarly, global ischemia (I) for 20 min followed by 45 minutes of reperfusion (R) produced no sustained effects on the final recovery of any of these parameters in any group of hearts perfused in the absence of blood cells. However, I/R hearts perfused with either PMNs or platelets alone exhibited decreases in these variables of $5{\sim}10%$ (p＜0.05 from control). Furthermore, I/R hearts perfused with both PMNs and platelets exhibited decreases of 50 to 60% in all measurements of cardiac function (p＜0.01). These dual cell perfused I/R hearts also exhibited marked increases in cardiac myeloperoxidase (MPO) activity indicating a significant PMN infiltration, and enhanced P-selectin expression on the coronary microvascular endothelium. All cardiaodynamic effects as well as PMN accumulation and P-selectin expression were markedly attenuated by a recombinant soluble PSGL-1 which inhibits selectin mediated cell adhesion. These results provide evidence that platelets and PMNs act synergistically in provoking post-reperfusion cardiac dysfunction, and that this may be largely due to cell to cell interactions mediated by P-selectin. These results also demonstrate that a recombinant soluble PSGL-1 reduces myocardial reperfusion injury by platelet and PMNs interaction.

• The Korean Journal of Physiology
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• v.30 no.1
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• pp.105-116
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• 1996

Rendering the brain ischemic would evoke the cerebral ischemic reflex which is characterized by an arterial pressor response, apnea and bradycardia. Since the rostral ventrolateral medulla (RVLM) is known to play a key role in the maintenance of normal cardiopulmonary activity, during the cerebral ischemic reflex some cardiac related cells should be excited and respiration related cells inhibited. In this context, the responses of RVLM neurons to systemie and focal hypoxia were analyzed in the present study. Twenty-five adult cats of either sex were anesthetized with ${\alpha}-chloralose$ and the single neuronal activities were identified from RVLM area. For the induction of focal hypoxia in the recording site, sodium cyanide was applied iontophoretically and for systemic hypoxia the animal was ventilated with nitrogen gas for a twenty-second period. Cellular activities were analyzed in terms of their discharge pattern and responses to the hypoxia by using post-stimulus time and single-pass time histograms. Of eighteen cardiac related cells recorded from the RVLM area, twelve cells were excited by iontophoresed sodium cyanide and of twenty-five respiration related cells, fourteen cells were excited by iontophoresed sodium cyanide. Remaining cells were either inhibited or unaffected. Eight of fifteen cells tested with iontophoresed sodium lactate were excited and remaining seven cells were inhibited. Systemic hypoxia induced by nitrogen gas inhalation elevated the arterial blood pressure, but excited, inhibited or unaffected the single neuronal activities. Some cells showed initial excitation followed by inhibition during the systemic hypoxia. Bilateral vagotomy resulted in a decrease of arterial pressor response to the systemic hypoxia, and a slight decrease in the rhythmicity related to cardiac and/or respiratory rhythms. The single neuronal responses to either systemic or focal hypoxia were not affected qualitatively by vagotomy. From the above results, it was concluded that the majority of the cardiac- and respiration- related neurons in the rostral ventrolateral medulla be excited by hypoxia, not through the mediation of peripheral chemoreceptors, and along with the remaining inhibited cells, all these cells be involved in the mediation of cerebral ischemic reflex.

• Korean Journal of Microbiology
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• v.44 no.4
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• pp.282-288
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• 2008

Tissue ischemia resulting from the constriction or obstruction of blood vessels leads to an illness that may affect many organs including the heart, brain, and legs. In recent years, considerable progress has been made in the field of therapeutic angiogenesis and the new approaches are expected to cure those "no-option patients" who are unsuited to conventional therapies. Although single angiogenic growth factor may be successful in inducing angiogenesis, combination of multiple growth factors is increasingly sought these days to augment the therapeutic responses. This trend is proper in light of the fact that blood vessel formation is a complex and multi-step process that requires the actions of many different factors. To meet the growing need for functionally significant blood flow recovery in the ischemic tissues, a novel strategy that can provide concerted actions of multiple factors is required. One way to achieve such a goal is to use a transcription factor that can orchestrate the expression of multiple target genes in the ischemic region and thus induce significant level of angiogenesis. Here, a putative transcription factor, cardiac ankyrin repeat protein (CARP), was evaluated in adenoviral vector context for angiogenic activity in human umbilical vein endothelial cells. The results indicated significant increase in proliferation, capillary-like structure formation, and induction of vascular endothelial growth factor, a typical angiogenic gene. Taken together, these results suggest that CARP represents itself as a novel target for therapeutic angiogenesis and warrants further investigation.

• Journal of Ginseng Research
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• v.44 no.3
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• pp.483-489
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• 2020

Background: Korean Red Ginseng (KRG) has been known to possess many ginsenosides. These ginsenosides are used for curing cardiovascular problems. The present study show the protective potential of KRG against doxorubicin (DOX)-induced myocardial dysfunction, by assessing electrocardiographic, hemodynamic, and biochemical parameters and histopathological findings. Methods: Animals were fed a standard chow and adjusted to their environment for 3 days before the experiments. Next, the rats were equally divided into five groups (n = 9, each group). The animals were administered with KRG (250 and 500 mg/kg) for 10 days and injected with DOX (20 mg/kg, subcutaneously, twice at a 24-h interval) on the 8th and 9th day. Electrocardiography and echocardiography were performed to study hemodynamics. Plasma levels of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde were measured. In addition, the dose of troponin I and activity of myeloperoxidase in serum and cardiac tissue were analyzed, and the histopathological findings were evaluated using light microscopy. Results: Administration of KRG at a dose of 250 and 500 mg/kg recovered electrocardiographic changes, ejection fraction, fractional shortening, left ventricular systolic pressure, the maximal rate of change in left ventricle contraction (-dP/dt_max), and left ventricle relaxation (-dP/dt_max). In addition, KRG treatment significantly normalized the oxidative stress markers in plasma, dose dependently. In addition, the values of troponin I and myeloperoxidase were ameliorated by KRG treatment, dose dependently. And, KRG treatment showed better histopathological findings when compared with the DOX control group. Conclusion: These mean that KRG mitigates myocardial damage by modulating the hemodynamics, histopathological abnormality, and oxidative stress related to DOX-induced cardiomyopathy in rats. The results of the present study show protective effects of KRG on cardiac toxicity.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.283-289
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• 2013

This study was designed to evaluate the protective effect of Korean red ginseng (KRG) against ischemia/reperfusion (I/R) injury in isolated guinea pig heart. KRG has been shown to possess various ginsenosides, which are the major components of Panax ginseng. These components are known naturally occurring compounds with beneficial effects and free radical scavenging activity. The heart was induced to ischemia for 60 min, followed by 120 min reperfusion. The hearts were randomly allocated into five groups (n=8 for each group): normal control (N/C), KRG control, I/R control, 250 mg/kg KRG group and 500 mg/kg KRG group. KRG significantly increased hemodynamics parameters such as aortic flow, coronary flow and cardiac output. Moreover, KRG significantly increased left ventricular systolic pressure (LVSP), the maximal rate of contraction (+dP/$dt_{max}$) and maximal rate of relaxation (-dP/$dt_{max}$). Also, treatment of KRG ameliorated electrocardiographic index such as the QRS, QT and RR intervals. Moreover, KRG significantly suppressed the lactate dehydrogenase, creatine kinase-MB fraction and cardiac troponin I and ameliorated the oxidative stress markers such as malondialdehyde and glutathione. KRG was standardized through ultra performance liquid chromatograph analysis for its major ginsenosides. Taken together, KRG has been shown to prevent cardiac injury by normalizing the biochemical and oxidative stress.

• Journal of the Korean Dietetic Association
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• v.8 no.3
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• pp.250-259
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• 2002

The purpose of this study was to confirm that calcium intake and healthy status play a role in reducing the risk of cardiovascular disease, to assure that calcium intake and regular exercise are important in reducing serum lipid levels in middle-aged women. Daily nutrient intakes were analyzed by convenient method. Anthropometric measurement such as body weight and height and blood pressure were measured. The subjects divided into two groups : women in group I under 50 years of age($\leq$49 yr group) and those in group II 50 years up($\geq$50 yr group). Average ages of group I and II were 43.87 and 53.46 years. The nutrients intake of subjects were higher than Korean recommended dietary allowances(KRDA) except calorie, iron, calcium, vitamin B1. They showed significant difference each other in vitamin B2(p<0.05), calcium(p<0.01) intake. Mean daily calcium intake was 540.88mg in $\leq$49 yr group and 519.50mg in $\geq$50 yr group. The levels of serum cholesterol, triglyceride, blood pressure, Atherogenic Index(AI), LDL/HDL and Cardiac Index(CI) were increased with age. The triglyceride and total cholesterol concentrations and LDL/HDL in $\geq$50 yr group were significantly higher than those of $\leq$49 yr group. There was a highly significantly positive correlation between age and triglyceride, total cholesterol and Atherogenic Index(AI). Triglyceride, total cholesterol, LDL-cholesterol concentration and Atherogenic Index(AI) were positively correlated with body weight and WHR(waist-hip ratio). Also ther was a significantly negative correlation between exercise and Cardiac Index(CI). Also a significantly negative correlation was found between Ca intake and LDL-cholesterol. Exercise and Cardiac Index(CI) also had a significantly negative relation. The results suggest that increased habitual physical activity and calcium intake should be recommended as a way of decreasing blood lipids and blood pressure in middle-aged women.

• The Korean Journal of Physiology
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• v.22 no.1
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• pp.1-12
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• 1988

The changes in membrane potential and intracellular $Ca^{2+}$ activities along with adenosine triphosphate (ATP) and creatine phosphate (CP) contents of guinea pig hearts were studied during the cardioplegia and recovery phase. The results obtained were summarized as follows: 1) A low concentration of $Ca^{2+}$ in the cardioplegic solution caused significant changes in membrane potential during the cardioplegia and action potential configurations of the first beat after cardioplegia. 2) Intracellular $Ca^{2+}$ activities were decreased significantly during cardioplegia and increased when the cardiac tissue was reperfused with the normal Tyrode solution. The magnitude of increase in intracellular $Ca^{2+}$ activities was larger in the 0.1 mM $Ca^{2+}-cardioplegic$ solution than the 1.8 mM $Ca^{2+}-solution$. 3) ATP and CP contents of cardiac ventricular tissue were decreased during the cardioplegia, regardless of $Ca^{2+}$ concentration in the cardioplegic solutions, and CP contents were recovered with the reperfusion of normal Tyrode solution faster than those of ATP. And, there were no significant differences in the recovery of CP contents with different concentrations of $Ca^{2+}$ in the cardioplegic solutions tested, while the recovery of ATP contents was faster with $15mM\;K^{+},\;0.1mM\;Ca^{2+}$ cardioplegic solution. These results suggest that the $Ca^{2+}$ concentration in the cardioplegic solution is one of major factors influencing the recovery of cardiac tissue from the cardioplegia.

• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.316-321
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• 1995

All the pharmacological studies of LB17522 described here were carried out with high doses (fifteen to sixty times of the therapeutic dose) to determine an indication of potential side effects in clinical use in terms of the acute clinical signs, cardiovascular and central nervous system. LB10522 does not produce any observable clinical signs except for the symptoms such as moist eye, skin rash, slight salivation, vomitting, and slightly reduced activity. The effects of LB10522 on the hemodynamics and cardiac function of anesthetized beagle dogs are as follows; heart rates and mean arterial blood pressure had a tendency to increase mildly, which is a normal finding in anesthetized dogs. All the animals except for one showed relatively stable respiratory rates throughout the observation period. Each animal treated with LB10522 showed slight increase in the left cardiac work and left ventricular stroke work which are mainly related to corresponding increases in cardiac output. Femoral blood flow were shown to be increased in some animals treated with LB10522. The epileptogenic activities of various cephalosporins were assessed by a direct intracerebral injection of appropriate concentration of test articles. The CD$_{50}$ values (nmol) obtained from the analysis of the dose-response data are as follows; 78.2, 175.3, 156.3, and 53.5 for cefazolin, cephaloridine, ceftazidime, and LB 10522, respectively. LB10522 seems to be equipotent with cefazolin or to be three times more potent than cephaloridine and ceftazidime in causing adverse CNS stimulation. Taken into consideration all the information obtained, LB10522 is not supposed to induce much changes in the functions examined in these studies in man at therapeutic doses.s.