• Journal of Ginseng Research
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• v.44 no.2
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• pp.258-266
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• 2020

Background: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study. Methods: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein. Results: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (-6.426 kcal/mol), and the binding was stable. GRb1 significantl reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro, with a half-maximal effective concentration of ≈2.317 μM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells. Conclusion: GRb1 is a potential natural GR agonist that protects against oxidative stress-induced apoptosis of H9C2 cells.

• Journal of Chest Surgery
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• v.55 no.1
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• pp.69-76
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• 2022

Background: While the use of bioprosthetic valves for mitral valve replacement (MVR) is increasing, very few studies have compared bovine pericardial and porcine valves in the mitral position to help guide bioprosthetic selection. Methods: In the present study, patients who underwent MVR using bovine pericardial valves were compared with those who underwent MVR with porcine bioprostheses between January 1996 and July 2018. Those with prior MVR, infective endocarditis, congenital mitral valve disease, or ischemic mitral regurgitation were excluded. The primary outcomes were structural valve deterioration (SVD) and mitral valve reoperation from any cause, and death was regarded as a competing risk. Competing risk analysis and propensity score-matching were used for comparisons. Results: Among the 388 patients enrolled, pericardial and porcine bioprostheses were implanted in 217 (55.9%) and 171 (44.1%), respectively. Propensity score-matching yielded 122 pairs of patients that were well-balanced for all baseline covariates. No significant differences were observed between the groups in unadjusted (p=0.09) and adjusted overall survival (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.72-1.76; p=0.60). Competing risk analysis revealed no significant differences in the risks of mitral reoperation (HR, 1.07; 95% CI, 0.50-2.27; p=0.86) and development of SVD (HR, 1.57; 95% CI, 0.56-4.36; p=0.39) between the groups. Matched population analysis confirmed similar results regarding reoperation (HR, 0.99; 95% CI, 0.40-3.22; p=0.98) and SVD (HR, 1.39; 95% CI, 0.41-4.73; p=0.60). Conclusion: No significant differences in survival or valve durability were observed between bovine pericardial and porcine bioprosthetic MVR. These findings require further validation through studies with larger sample sizes.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.281-292
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• 2023

Background and Objectives: Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (CM) hold great promise as a cellular source of CM for cardiac function restoration in ischemic heart disease. However, the use of animal-derived xenogeneic substances during the biomanufacturing of hiPSC-CM can induce inadvertent immune responses or chronic inflammation, followed by tumorigenicity. In this study, we aimed to reveal the effects of xenogeneic substances on the functional properties and potential immunogenicity of hiPSC-CM during differentiation, demonstrating the quality and safety of hiPSC-based cell therapy. Methods and Results: We successfully generated hiPSC-CM in the presence and absence of xenogeneic substances (xeno-containing (XC) and xeno-free (XF) conditions, respectively), and compared their characteristics, including the contractile functions and glycan profiles. Compared to XC-hiPSC-CM, XF-hiPSC-CM showed early onset of myocyte contractile beating and maturation, with a high expression of cardiac lineage-specific genes (ACTC1, TNNT2, and RYR2) by using MEA and RT-qPCR. We quantified N-glycolylneuraminic acid (Neu5Gc), a xenogeneic sialic acid, in hiPSC-CM using an indirect enzyme-linked immunosorbent assay and liquid chromatography-multiple reaction monitoring-mass spectrometry. Neu5Gc was incorporated into the glycans of hiPSC-CM during xeno-containing differentiation, whereas it was barely detected in XF-hiPSC-CM. Conclusions: To the best of our knowledge, this is the first study to show that the electrophysiological function and glycan profiles of hiPSC-CM can be affected by the presence of xenogeneic substances during their differentiation and maturation. To ensure quality control and safety in hiPSC-based cell therapy, xenogeneic substances should be excluded from the biomanufacturing process.

• Journal of Chest Surgery
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• v.31 no.11
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• pp.1049-1055
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• 1998

Background: Coronary artery bypass surgery is an important treatment for ischemic heart disease. Recently operative mortality and morbidity has decreased, however further improvement is necessary. Materials and methods: This study was designed to evaluate the risk of operative mortality and morbidity by retrospective method. From 1992 to 1997, eighty six patients underwent coronary artery bypass surgery. There were 61 males and 25 females aged 36~74 years(mean, 58.6). Fourteen patients(16%) had previous PTCA or stent insertion, 41 patients(48%) had unstable angina, and 45 patients(52%) had three vessel disease. Patients with low LV ejection fraction(<35%) were 7 cases and urgent or emergent operation were 10 cases. There were 6 cases of combined surgery which were mitral valve replacement(2 cases), aortic valve replacement(2 cases), ASD repair(1 case), and VSD repair(1 case). Average number of distal anastomosis was 3.5 per patient and average aortic cross clamp time was 115±38.3min. Preoperative risk factors were defined as follows: female, old age(>70 years), low body surface area(<1.5M2), PTCA or stent insertion history, hypercholesterolemia, smoking, hypertension, DM, COPD, urgent or emergent operation, left main disease, low LV ejection fraction(<35%), and combined surgery. Results: Operative mortality was 7cases(8%). As a postoperative morbidity, perioperative myocardial infarction was 6 cases, cerebrovascular accident 6 cases, reoperation for bleeding 5 cases, acute renal failure 4 cases, gastrointestinal complication 3 cases, and mediastinitis 3 cases. In the evaluation of operative risk factors, low body surface area, DM and low LV ejection fraction were found to be predictive risk factors of postoperative morbidity(p<0.05), and low ejection fraction was especially a risk factor of hospital mortality(p<0.05). Conclusions: In this study, low body surface area, DM and low LV ejection fraction were risk factors of postoperative morbidity and low ejection fraction was a risk factor of hospital mortality.

• Journal of Preventive Medicine and Public Health
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• v.30 no.4 s.59
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• pp.697-707
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• 1997

This study was performed to estimate the quantity of the effects of tobacco price raise on the smoking rate, and the smoking attributable deaths in Korea. The data were collected by questionnaire survey from 538 male of male workers. The questionnaire contained items on age, sex, living place, status of education, smoking history, the intention to quit smoking when the tobacco price be raised. The questionnaire, were distributed to the offices of enterprises, hospitals, research centers, and public agencies and then collected. Data were analyzed by using the age specific smoking rate, relative risks of eight major smoking related diseases, vital statistics, and the population attributable risk of deaths of smoking males. On the other hand, the impact of the tobacco price raise on the population attributable risk of death due to smoking in Korea was estimated by applying the presumed smoking rate after the price raise. The results obtained were as follows: 1. The smoking rate of male white color workers in large cities was 59.5%. 2. The proportion of male smokers who has the intention to quit smoking when the tobacco price be raised was 61.5%. 3. The proportion of male smokers who has the intention to quit smoking if the price of tobacco be raised was proportional to the degree of increasing tobacco price. It is estimated that if the tobacco price were raised more than four times as now, the presumed smoking rate goes down as low as 26.7%. If the tobacco price be raised 20% each year, presumed smoking rate is 46.2%. 4. The number of attributable male death of smoking estimated by using 8 major smoking related diseases(lung cancer, laryngeal cancer, esophageal cancer, stomach cancer, pancreatic cancer, cerebrovascular disease, ischemic heart disease, chronic obstructive pulmonary disease) was 25,863 death each year. That is 20.1% of total age over 20 male deaths. 5. f the tobacco price were raised more than four times as now and all smokers who has intention to quit smoking quits smoking, 12,336 lives, or 47.7% of smoking related deaths could be saved. 6. IF the actual practice rate of quitting smoking among male smokers with intention to stop smoking when the price of tobacco be raised is 10%, 25%, or 50%, then the expected decrease of death numbers when the tobacco price were raised more than four times as now can be 1,112, 3,483, 5,796 respectively.

• Tuberculosis and Respiratory Diseases
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• v.54 no.3
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• pp.311-319
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• 2003

Background : Previous studies have suggested that a B-type natriuretic peptide(BNP) test can provide important information on diagnosis, as well as predicting the severity and prognosis of heart failure. Myocardial dysfunction is often observed in critically ill noncardiac patients admitted to the Intensive Care Unit, and the prognosis of the myocardial dysfunction needs to be determined. This study evaluated the predictability of BNP on the prognosis of critically ill noncardiac patients. Methods : 32 ICU patients, who were hospitalized from June to October 2002 and in whom the BNP test was evaluated, were enrolled in this study. The exclusion criteria included the conditions that could increase the BNP levels irrespective of the severity, such as congestive heart failure, atrial fibrillation, ischemic heart disease, and renal insufficiencies. A triage B-Type Natriuretic Peptide test with a RIA-kit was used for the fluorescence immunoassay of BNP test. In addition, the acute physiology and the chronic health evaluation (APACHE) II score and mortality were recorded. Results : There were 16 males and 16 females enrolled in this study. The mean age was 59 years old. The mean BNP levels between the ICU patients and control were significantly different ($186.7{\pm}274.1$ pg/mL vs. $19.9{\pm}21.3$ pg/mL, p=0.033). Among the ICU patients, there were 14(44----) patients with BNP levels above 100 pg/mL. The APACHE II score was $16.5{\pm}7.6$. In addition, there were 11 mortalities reported. The correlation between the BNP and APACHE II score, between the BNP and mortality were significant (r=0.443, p=0.011 & r=0.530, p=0.002). The mean BNP levels between the dead and alive groups were significantly different ($384.1{\pm}401.7$ pg/mL vs. $83.2{\pm}55.8$ pg/mL p=0.033). However, the $PaO_2/FiO_2$ did not significantly correlate with the BNP level. Conclusion : This study evaluated the BNP level was elevated in critically ill, noncardiac patients. The BNP level could be a useful, noninvasive tool for predicting the prognosis of the critically ill, noncardiac patients.

• Radiation Oncology Journal
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• v.25 no.1
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• pp.26-33
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• 2007

[ $\underline{Purpose}$ ]: The aim of this study is to evaluate and compare the incidence and aspects of myocardial perfusion defects in patients who were subjected to either two-dimensional or three-dimensional simulation techniques for early left-sided breast cancer. The myocardial perfusion defects were determined from using single photon emitted computerized tomography (SPECT) myocardial perfusion images. $\underline{Materials\;and\;Methods}$: Between January 2002 and August 2003, 32 patients were enrolled in this study. The patients were diagnosed as having early (AJCC stage T1-T2N0M0) left-sided breast cancer and were treated with tangential irradiation after breast-conserving surgery and systemic chemotherapy. The patients were divided into two groups according to the type of simulation received: two-dimensional simulation using an X-ray fluoroscope simulator or three-dimensional simulation with a CT simulator. All patients underwent technetium-99m-sestamibi gated perfusion SPECT at least 3 years after radiotherapy. The incidence and area of myocardial perfusion defects were evaluated and were compared in the two groups, and at the same time left ventricular ejection fraction and cardiac wall motion were also analyzed. The cardiac volume included in the radiation fields was calculated and evaluated to check for a correlation between the amount of irradiated cardiac volume and aspects of myocardial perfusion defects. $\underline{Results}$: A myocardial perfusion defect was detected in 11 of 32 patients (34.4%). There were 7 (46.7%) perfusion defect cases in 15 patients who underwent the two-dimensional simulation technique and 4 (23.5%) patients with perfusion defects in the three-dimensional simulation group (p=0.0312). In 10 of 11 patients who had myocardial perfusion changes, the perfusion defects were observed in the cardiac apex. The left ventricular ejection fraction was within the normal range and cardiac wall motion was normal in all patients. The irradiated cardiac volume of patients in the three-dimensional simulation group was less than that of patients who received the two-dimensional simulation technique, but there was no statistical significance as compared to the incidence of perfusion defects. $\underline{Conclusion}$: Radiotherapy with a CT simulator (three-dimensional simulation technique) for early left-sided breast cancer may reduce the size of the irradiated cardiac volume and the incidence of myocardial perfusion defects. Further investigation and a longer follow-up duration are needed to analyze the relationship between myocardial perfusion defects and clinical ischemic heart disease.

• Tuberculosis and Respiratory Diseases
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• v.56 no.4
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• pp.364-373
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• 2004

Background : Obstructive sleep apnea is a contributory factor of hypertension, arrhythmia, ischemic heart disease and other cardiovascular diseases. However, the pathophysiology underlying this relationship is unclear. Recent reports have shown that the soluble intercellular adhesion molecule-1(sICAM-1) and vascular endothelial growth factor(VEGF) are involved in the initiation and progression of atherosclerosis, and some reports state that increased levels of these cytokines are found in patients with obstructive sleep apnea. In this study, the levels of sICAM-1 and VEGF were measured in patients with obstructive sleep apnea in order to determine if obstructive sleep apnea is involved in the pathophysiology of cardiovascular diseases. Methods : Thirty-seven patients were chosen amongst a population who visited the Sleep Disorders Clinic of St. Paul's Hospital in Seoul, Korea for a diagnosis of obstructive sleep apnea and who had subsequently undergone an overnight polysomnography at the clinic. The sera from these patients were retrieved after an overnight polysomnography session and the samples were kept at $-70^{\circ}C$. The cytokine levels were determined with ELISA and the relationships between the serum levels of sICAM-1 and VEGF along with polysomnography parameters were analyzed. Results : No statistically significant correlation was observed between the sICAM-1 levels and the apnea-hypopnea index(r=0.27, P>0.05). Positive correlations were found between the apnea-hypopnea index and serum VEGF levels (r=0.50, P<0.01), the apnea index and the serum sICAM-1 levels (r=0.31, P<0.01), and the apnea index and the serum VEGF levels (r=0.45, P<0.01). Conclusions : Obstructive apnea or hypopnea leads to an increase in the sICAM-1 and VEGF levels. Such an increase in the cytokine levels most likely leads to the higher incidence of cardiovascular diseases observed in patients with obstructive sleep apnea.

• Journal of Korean Academy of Nursing
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• v.28 no.1
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• pp.117-131
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• 1998

The purpose of this study was to develop a critical pathway for case management for patients who have received Coronary Artery Bypass Graft (CABG) because of Ischemic Heart Disease(IHD) which is a factor of rising medical expenses. For this study. a conceptual framework was developed through a review of the literature including six critical pathways which are currently being used in USA. In order to identify the overall service contents required by these patients and to draw up a preliminary critical pathway, 30 cases of medical records of patients who had CABG because of IHD between January, 1995 to June. 1996 at the Cardiovascular Center of Yonsei Medical Center in Seoul were analyzed. An expert validity test was done for the preliminary critical pathway and clinical validity test was also done using seven IHD patients with CABG between November 11 and 23, 1996. After these processes. the final critical pathway was developed. The results of this study are summarized as follows : 1. The vertical axis of the critical pathway includes the following eight items : tests, nutrition, medications, consultations, activity, assessments, treatments, education discharge planning and the horizontal axis includes the time from the start of hospitalization to discharge. 2. Analysis of the 30 medical records indicated that the average length of stay was 20.2days with the average length of stay from hospitalization day to operation day being 6.2 days, and the average length of stay from operation day to discharge day was 13. 9 days. Analysis of the service contents showed that the horizontal axis of the preliminary critical pathway was set from hospitalization to the 14th post operation day and the vertical axis was set to include eight items, the contents which ought to have occurred, according to the time frames of the horizontal axis. 3. As a result of the experts validity, it was found that among the total of 571 items. there was over 83% agreement for 482 items, less than 83% for 89 items, which were then deleted and a revision of the critical pathway was done. 4. A clinical validity test was done using seven IHD patients with CABG. During the process, three patients were deleted because they were out of the criteria the investigator set. Finally, four patients were used. The result of study indicated that only one patient was discharged on the tenth post operation day, which was one day later than the expected day. Three patients were discharged later than the expected day from three days to nine days. All the cases progressed on schedule until the operation day and the first post operation day, but from the second post operation days, there were differences between the critical pathway and the actual practice. The differences came from tests, assessments, and treatments. 5. On the basis of the results of the clinical validity test. the following revisions in the final critical pathway were made : the transfer from ICU to step down ward would be the second post operation day, and the transfer to a general ward, the fifth post operation day, for patients who complained of lack of sleep from the fifth post operation day to discharge, a sleeping pill would be prescribed, skin observations would be performed routinely from immediately after the operation until the third post operation day, and would continue if there was a sign of skin injury on the fourth post operation day, and assessment of chest pain would be done from the third post operation day, and the “stairs climbing” item, expected to be done on the ninth post operation day would be deleted. In conclusion, this critical pathway is partially applicable to the care of patients with CABG but there are some parts needed to be further investigated.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.404-415
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• 1998

Background: Sleep apnea syndrome, which occurs in 1~4 % of the adult population, frequently has different cardiovascular complications such as hypertension, ischemic heart disease, cardiac arrythmia as well as sleep-wake disorder such as excessive daytime hypersomnolence or insomnia. Mortality and vascular morbidity are reported to be significantly higher in sleep apnea syndrome patients than in normal population. According to the recent studies, autonomic dysfunction as well as hypoxemia, hypercapneic acidosis, and increased respiratory effort, may playa role in the high prevalence of cardiovascular complications in patients with sleep apnea syndrome. However the cause and mechanism of autonomic neuropathy in patients with sleep apnea syndrome are not well understood. We studied the existence of autonomic neuropathy in patients with sleep apnea syndrome and factors which influence the pathogenesis of autonomic neuropathy. Method: We used the cardiovascular autonomic neuropathy(CAN) test as a method for evaluation of autonomic neuropathy. The subjects of this study were 20 patients who diagnosed sleep apnea syndrome by polysomnography and 15 persons who were normal by polysomnography. Results: Body mass index and resting systolic blood pressure were higher in sleep apnea group than control group. Apnea index(Al), respiratory disturbance index(RDI) and snoring time percentage were significantly higher in sleep apnea group compared with control group. But there were no significant differences in saturation of oxygen and sleep efficiency in two groups. In the cardiac autonomic neuropathy test, the valsalva ratio was significantly low in sleep apnea group compared with control group but other tests had no differences between two groups. The CAN scores and corrected QT(QTc) interval were calculated significantly higher in sleep apnea group, but there were no significant correlations between CAN scores and QTc interval. There were no significant data of polysomnography to correlate to the CAN score. It meant that the autonomic neuropathy in patients with sleep apnea was affected by other multiple factors. Conclusion: The cardiovascular autonomic neuropathy test was a useful method for the evaluation of autonomic neuropathy in patients with sleep apnea syndrome and abnormalities of cardiovascular autonomic neuropathy were observed in patients with sleep apnea syndrome. However, we failed to define the factors that influence the pathogenesis of autonomic neuropathy of sleep apnea syndrome. This study warrants futher investigations in order to define the pathogenesis of autonomic neuropathy in patients with sleep apnea syndrome.