• Biomedical Science Letters
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• v.12 no.3
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• pp.289-301
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• 2006

Cardiopulmonary bypass (CPB) for cardiac surgery triggers the production and release of numerous chemotactic substances and cytokines, ensuing systemic inflammatory response that leads to postoperative major organ dysfunction. Traditionally, corticosteroids (steroid) have been administered to patients undergoing cardiac surgery to ward off these detrimental physiologic alterations. However, the majority of the studies have been performed on adult patients with high-dose steroid. We carried out a randomized, prospective, double-blind study to compare the efficacy of low-dose steroid with that of high-dose steroid and to determine the adequate dose of pretreated-steroid for prophylactic effects in pediatric cardiac surgery. Thirty pediatric patients scheduled for elective cardiac surgery were randomly assigned to two groups; fifteen patients received low-dose methylprednisolone (10mg/kg intravenously, n=15, low-dose group) and the others received high-dose methylprednisolone (30mg/kg intravenously, n=15, high-dose group) 1 hour prior to CPB. Arterial blood samples were taken before CPB (Pre-CPB), 10 minutes after start of CPB (CPB-10), and immediately after CPB-end (CPB-OFF) for measuring total leukocyte counts (T-WBC) and diff-counts, platelet counts, interleukin-6 (IL-6), myeloperoxidase (MPO), total antioxidant (TAO), neuron-specific enolase (NSE), troponin I (TNI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) levels. Other parameters such as volumes of urine output, pulmonary index $(PI,\;PaO_2/FiO_2)$, mechanical ventilating period, intensive care unit (ICU)-staying period, postoperative complications (fever, wound problem), postoperative 24 hrs and total volumes in blood loss, and hospitalized days were also assessed. All parameters were compared between two groups. There were no significant differences in T-WBC counts, monocyte fraction, platelet counts, TA levels, NSE levels, creatinine levels, BUN levels, the volumes of total urine output, PI, the incidences of fever and wound problem, postoperative 24hrs- and total-blood loss volumes and ICU-staying period between two groups (P>0.05). At CPB-OFF, neutrophil fraction, MPO level, TNI level, and AST level were higher in the high-dose group than in the low-dose group (P<0.05). IL-6 level at CPB-10 was higher in the high dose-group than in the low-dose group (P<0.05). Furthermore, mechanical ventilating periods and hospitalized days of the high-dose group were significantly longer than those of low-dose group (P<0.05). The high-dose group had significantly low lymphocyte fi-action at CPB-OFF compared with the low-dose group (P<0.001). These findings suggest that pretreatment of high-dose steroid is not superior to that of low-dose steroid regrading its potential benefits in pediatric cardiac surgery. Therefore, the conventional strategy of steroid treatment, high-dose pretreatment, should be modified in the cardiac surgery with CPB. However, further studies must be performed on the larger number of patients in as much as small number of patients in this study.

• The Korean Journal of Health Service Management
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• v.7 no.3
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• pp.71-82
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• 2013

Arterial stiffness(AS) is an important pathologic state of vascular injury. This study was carried out to elucidate the effect of physiological variables on brachial-ankle pulse wave velocity(BAPWV), index of AS. Four hundred adults(volunteers) participated in this study. Body indices, biochemical, cardiac and inflammatory markers, and right(Rt)- and left(Lt)-BAPWV were measured. Body mass index(BMI), Rt- and Lt-BAPWV, glucose, triglyceride, alkaline phosphatase(ALP), gamma-glutamyl transferase(GGT), creatinine, uric acid, troponin-I(TNI), NT-proBNP and high sensitivity C-reactive protein(hs-CRP) levels were higher than the reference value of each variable. Rt- and Lt-BAPWV were directly correlated with age, body weight, BMI, glucose, ketone, aspartate aminotransferase, alanine aminotransferase, ALP, GGT, total cholesterol, low density lipoprotein, lipoprotein(a), apolipoprotein-B, blood urea nitrogen, heart rate, TNI, creatine kinase, CK-MB, lactic dehydrogenase, myoglobin, hs-CRP, lipase, reumatoid factor, fibrinogen and D-dimer (P<0.05, P<0.01, P<0.001 or P<0.000, respectively), but inversely associated with total bilirubin, uric acid, apolipoprotein-A1 and GFR (P<0.05). These observations suggest that a variety of physiological variables may influence BAPWV, resulting in increased risk or prevention of cardiovascular and/or cerebrovascular attacks. Therefore, physiological variables affecting BAPWV should be regularly controlled.

• Clinical and Experimental Pediatrics
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• v.60 no.11
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• pp.365-372
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• 2017

Purpose: The mechanism for the pathogenesis of adriamycin (ADR)-induced cardiomyopathy is not yet known. Different hypotheses include the production of free radicals, an interaction between ADR and nuclear components, and a disruption in cardiac-specific gene expression. Apoptosis has also been proposed as being involved in cardiac dysfunction. The purpose of this study was to determine if apoptosis might play a role in ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were separated into 2 groups: the control group (C group) and the experimental group (ADR 5 mg/wk for 3 weeks through intraperitoneal injections; A group). Echocardiographic images were obtained at week 3. Changes in caspase-3, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), interleukin (IL)-6, tumor necrosis $factor-{\alpha}$, brain natriuretic peptide (BNP), troponin I, collagen 1, and collagen 3 protein expression from the left ventricle tissues of C and A group rats were determined by Western blot. Results: Ascites and heart failure as well as left ventricular hypertrophy were noted in the A group. Ejection fraction and shortening fraction were significantly lower in the A group by echocardiography. The expression of caspase-3, Bax, IL-6, BNP, collagen 1, and collagen 3 were significantly higher in the A group as compared with the C group. Protein expression of Bcl-2 decreased significantly in the A group compared with the C group. Conclusion: ADR induced an upregulation of caspase-3, Bax, IL-6, and collagen, as well as a depression in Bcl-2. Thus, apoptosis and fibrosis may play an important role in ADR-induced cardiomyopathy.

• Development and Reproduction
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• v.11 no.3
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• pp.167-177
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• 2007

In the present study, we isolated three human adult stem cells including adipose tissue-derived stem cells(HAD), umbilical cord-derived stem cells(HUC), and amnion-derived stem cells(HAM) and analysed their characteristics. And we examined whether HAD could be used as therapeutical cells for the heart diseases. Both HAM and HUC appeared very similar morphology but HAD was different. Doubling time of HUC was most fast, but total doubling numbers of HUC was same with HAM. Total doubling numbers of HAD was much more than others. Expression patterns of genes and proteins of three human adult stem cells were very similar. Also they were differentiated into adipocytes, osteocytes, and chondrocytes. In addition, they expressed many cardiomyocyte-related genes. But expression pattern of genes is a little different. When HAD were cultivated in the presence or absence of various combinations of BMP and FGF after 5-azacytidine expose for 24 h, expression of Cmlc-1, and ${\alpha}1c$ genes was significantly increased. However, expression of troponin T, troponin I and Kv4.3 genes was not changed. Based on these observations, it is suggested that HAD, HUC, and HAM might be used as potentially therapeutical cells for clinical application.

• Journal of Chest Surgery
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• v.31 no.2
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• pp.125-133
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• 1998

This study was designed to identify the efficiency of serum troponin-T(s-TnT) level as a diagnostic indicator for the perioperative myocardial damage with open heart surgery(OHS) and to compare with the conventional myocardial enzyme tests such as isoenzyme fraction of creatine kinase(% CK-MB) and isoenzyme ratio of lactate dehydrogenase(LDH1/LDH2 ratio). The study was performed on 30 adult patients who underwent OHS from Jan. 1996 to June 1996 at Inje University Pusan Paik Hospital, and they were divided into two groups accor- ding to aortic clamping time(ACT) duration : group I(ACT＜60 minutes, n=15); group II (ACT＞60 minutes, n=15). S-TnT, % CK-MB, and LDH1/LDH2 ratio were measured in serial blood samples from all subjected patients. The results were obtained as follows. 1. In both groups, s-TnT concentrations increased gradually during OHS and elevated significantly at CPB-10(p＜0.001). The peak level was noticed at POD 1 in group I(1.10 $\pm$0.19 ng/ml), whereas, at CPB-off in group II(1.88$\pm$0.42 ng/ml). The elevated levels remained until POD 7 in both groups. 2. %CK-MB was risen significantly with the initiation of operations(p＜0.001) and the peak levels were noticed at CPB-off in both groups(7.14$\pm$0.86% in group I, 10.69$\pm$1.27% in group II). Thereafter, these levels returned to normal values at POD 3. 3. There were no significant changes in the values of LDH1/LDH2 ratio during and after OHS compared with the control levels(p＞0.05). 4. The serial changes of s-TnT were relatively well correlated with those of changes of % CK-MB(r=0.64, p＜0.05). 5. The serial s-TnT levels were significantly higher in group II than group I from B-ACR to POD 1(p＜0.05), suggesting that duration of aortic clamping time was a major factor concerned with perioperative myocardial injury. In conclusion, measurement of s-TnT is a very useful indicator in assessing the myocardial cell damage and therefore it is expected that serial checking and evaluation of the s-TnT is very available for identification of the perioperative myocardial damage and for postoperative cares in patients with OHS.

• Journal of Chest Surgery
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• v.39 no.5 s.262
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• pp.366-375
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• 2006

Background: Hypomagnesemia is a common complication after cardiac surgery with cardiopulmonary bypass. The purpose of this study was to assess the clinical beneficial effect of administration of magnesium sulfate in cardiac surgery. Material and Method: Thirty five patients scheduled for elective cardiac surgery were randomly assigned to magnesium group (n=20) which received magnesium sulfate in priming solution (1 g) and cardioplegic solution (1 g) or control group (n=15) which did not receive it. Arterial blood samples were drawn for measuring $Mg^{++}$ and electrolytes contents, blood gas analysis, CBC, total protein, albumin, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, tumor necrosis factor-${\alpha}$ $(TNF-{\alpha})$, interleukin-6 (IL-6), interleukin-10 (IL-10), creatine phosphokinase (CpK), creatine kinase-MB (CK-MB), lactate dehydrogenase(LDH), troponin-1 (TNI), prothrombin time (PT) and activated pratial thromboplastin time level (aPTT). Venous blood samples were drawn before and after the operation for measuring activated clotting time level (ACT). Result: $Mg^{++}$ levels in magensium group were higher than those of control group at intraoperative and post-operative periods (p<0.05). dysrhythmias were lower in magnesium group (8 cases out of 17 patients, 46.4%) than in control group (10 cases out of 10, 100%, p=0.050). Conclusion: These results showed that administration of low dose magnesium sulfate during cardiac surgery prevented hypomagnesemia and lowered incidence of dysrhythmia.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.4
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• pp.311-317
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• 2020

In the present experimental study, cecal ligation and puncture significantly increased the myocardial injury assessed in terms of excess release of creative kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL)-6 and decrease of IL-10 in the blood following 12 h of laparotomy procedure as compared to normal control. Also, a significant increase in protein expression levels of high-mobility group box 1 (HMGB1) and decreased phosphorylation of glycogen synthase kinase-3β (GSK-3β) was observed in the myocardial tissue as compared to normal control. A single independent administration of telmisartan (2 and 4 mg/kg) and AR-A014418 (1 and 2 mg/kg) substantially reduced sepsis-induced myocardial injury in terms of decrease levels of CK-MB, cTnI and IL-6, HMGB1, GSK-3β and increase in IL-10 and p-GSK-3β in the blood in sepsis- subjected rats. The effects of telmisartan at dose 4 mg/kg and AR-A014418 at a dose of 2 mg/kg were significantly higher than the telmisartan at a dose of 2 mg/kg and AR-A014418 1 mg/kg respectively. Further, no significant effects on different parameters were observed in the sham control group in comparison to normal. Therefore it is plausible to suggest that sepsis may increase the levels of angiotensin II to trigger GSK-3β-dependent signaling to activate the HMGB1/receptors for advanced glycation end products, which may promote inflammation and myocardial injury in sepsis-subjected rats.

• Clinical and Experimental Pediatrics
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• v.48 no.6
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• pp.640-648
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• 2005

Purpose : Kawasaki disease(KD) is known as an acute multi-systemic vasculitis with various immunologic abnormalities. Adhesion of leukocyte to endothelial cells is a key event in the sequence of inflammatory response. This study was performed to investigate the clinical significance of serum soluble intercellular adhesion molecule-1(sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in acute and subacute stages of typical KD for diagnostic and prognostic value. Methods : A typical KD group was 32 patients who were hospitalized from Jan. 2002 to Jun. 2004 was enrolled. Control was 16 non-KD patients with febrile illness. sICAM-1 and sVCAM-1 were measured and compared by Echocardiographic and clinical findings and cardiac troponin T and I. Results : sICAM-1 and sVCAM-1 levels of acute KD were significantly elevated over control(P=0.019 vs. P=0.049, respectively) and sICAM-1 was significantly decreased in subacute stage(P=0.0015). sICAM-1 and sVCAM-1 had positive correlation with each other in both stages(P=0.0067, P=0.015, retrospectively). Neither sICAM-1 nor sVCAM-1 correctly reflected the coronary abnormalities and responsiveness to intravenous gammaglobulin(IVGG) in both stages. But sVCAM-1 was significantly increased in the carditis group in both stages(P=0.025, P=0.014, retrospectively) and had a positive correlation with troponin T(r=0.63, P=0.00063). Conclusion : The levels of sICAM-1 and sVCAM-1 were not very useful tools for detecting and predicting subsequent coronary abnormalities and responsiveness to IVGG in KD patients. However, sVCAM-1 appears to play a significant role in carditis of KD. Further studies are needed about various adhesion molecules and cytokines in the pathogenesis of KD.

• Journal of Chest Surgery
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• v.38 no.1 s.246
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• pp.29-37
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• 2005

This study was prospectively designed to determine the physiologic effects of normothermic CPB and to compare its influences with hypothermic CPB. Material and Method: Thirty-six adult patients scheduled for el­ective cardiac surgery were randomly assigned to moderate hypothermic (hypothermic group nasopharyngeal tem­perature $26\~28^{\circ}C,\;n=18)$ ornormothermic (normothermic group, nasopharyngeal temperature > $35.5^{\circ}C\;n=18)$ CPB. Arterial blood samples were taken before CPB (Pre-CPB), 10 minutes after the start of CPB (CPB-10), and imme­diately after CPB stop (CPB-off) for determining total leukocyte counts, neuron-specific enolase (NSE), interleukin-6 (IL-6), endothelin-1 (ET-1), cortisol, troponin I (TNI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, blood urea nitrogen (BUN), and the pulmonary index $(Pi,\;PaO_{2}/FiO_{2}),$Other parameters such as urine output, mechanical ventilating period, ICU-staying period, postoperative complications and hospitalized days were also evaluated. Result: Total leukocyte counts, increased rate in NSE, in IL-6 and in cortisol at CPB-10 and CPB-off were significantly higher in normothermic group than in hyphothermic group. Urine output during CPB was lower in normothermic group than in hyphothermic group. The duration of mechanical ventilation, ICU-stay, and hospitalization were longer in normothermic group than in hyphothermic group. Conclusion: These findings sug­gested that normothermic CPB caused higher inflammatory and stress responses than hypothermic CPB during car­diac surgery using cold crystalloid cardioplegia. However, further studies with large number of cases should be carried out to validate this hypothesis.

• Korean Circulation Journal
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• v.53 no.6
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• pp.387-403
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• 2023

Background and Objectives: Myocardial ischemia and reperfusion injury (MIRI) has high morbidity and mortality worldwide. We aimed to explore the role of long noncoding RNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) in cardiomyocyte pyroptosis. Methods: Hypoxia/reoxygenation (H/R) injury was constructed in human cardiomyocyte (HCM). The level of LOXL1-AS1, miR-761, phosphatase and tensin homolog (PTEN) and pyroptosis-related proteins was monitored by quantitative real-time polymerase chain reaction or western blot. Flow cytometry examined the pyroptosis level. Lactate dehydrogenase (LDH), creatine kinase-MB and cardiac troponin I levels were detected by test kits. Enzyme-linked immunosorbent assay measured the release of inflammatory cytokines. Dual-luciferase assay validated the binding relationship among LOXL1-AS1, miR-761, and PTEN. Finally, ischemia/reperfusion (I/R) animal model was constructed. Hematoxylin and eosin staining assessed morphological changes of myocardial tissue. NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and casepase-1 expression was determined by immunohistochemistry. Results: After H/R treatment, LOXL1-AS1 and PTEN were highly expressed but miR-761 level was suppressed. LOXL1-AS1 inhibition or miR-761 overexpression increased cell viability, blocked the release of LDH and inflammatory cytokines (interleukin [IL]-1β, IL-18), inhibited pyroptosis level, and downregulated pyroptosis-related proteins (ASC, cleaved caspase-1, gasdermin D-N, NLRP3, IL-1β, and IL-18) levels in HCMs. LOXL1-AS1 sponged miR-761 to up-regulate PTEN. Knockdown of miR-761 reversed the effect of LOXL1-AS1 down regulation on H/R induced HCM pyroptosis. LOXL1-AS1 aggravated the MIRI by regulating miR-761/PTEN axis in vivo. Conclusions: LOXL1-AS1 targeted miR-761 to regulate PTEN expression, then enhance cardiomyocyte pyroptosis, providing a new alternative target for the treatment of MIRI.