• Clinical and Experimental Pediatrics
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• v.45 no.2
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• pp.208-213
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• 2002

Purpose : The major cause of cardiac dysfunction, after open heart surgery for congenital heart disease, is perioperative myocardial injury. Cardiac troponin I is found only within the myocardial cell, so it can be used as a biochemical marker of the myocardial injury. We performed this study to evaluate the worth of cardiac troponin I as a biochemical marker reflecting the extent of perioperative myocardial injury and recovery. Methods : Thirty-four patients who had undergone elective open heart surgery of congenital heart disease(CHD) from April to July 2001 were enrolled in this study. We measured types of CHD, serial cardiac troponin I(baseline 1 day before operation, postoperative day 1, 2, 3, 7), duration of cardiopulmonary bypass(CPB), aortic cross clamping(ACC), intubation and postoperative hospital stay. Results : Compared with the baseline before operation, there was a significant, increase of cardiac troponin I on the postoperative day 1 and a significant gradual decrease on the day 2, 3, 7. The levels of cardiac troponin I were the highest in the transposition of great artery(TGA) repair on the postoperative day 1 and high in the tetralogy of Fallot(TOF), atioventricular septal defect (AVSD), ventricular septal defect(VSD) and atrial septal defect(ASD) repair with decreasing sequence. The longer duration of CPB, ACC and intubation, the higher of cardiac troponin I, but there were no significant correlations between cardiac troponin I levels and duration of hospital stay. Conclusion : Because there was significant increases or decreases of cardiac troponin I according to the perioperative time and types of the congenital heart disease, it is a worthy biochemical marker which reflects the extent of perioperative myocardial injury and recovery after open heart surgery.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.4
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• pp.207-211
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• 2004

The purpose of the present study was to evaluate the expression of cardiac marker protein in rabbit cardiac tissue that was exposed to ischemic preconditioning (IPC), or ischemiareperfusion injury (IR) using two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). We compared 2DE gels of control (uninjured) cardiac tissue with those of IPC and IR cardiac tissue. Expression of one protein was detected in IR heart tissue, however the protein was not detected in the samples of control and IPC tissue. To further characterize the detected protein molecule, the protein in the 2D gel was isolated and subjected to trypsin digestion, followed by MALDI-MS. The protein was identified as myoglobin, which was confirmed also by Western blot analysis. These results are consistent with previous studies of cardiac markers in ischemic hearts, indicating myoglobin as a suitable marker of myocardial injury. In addition, the present use of multiple techniques indicates that proteomic analysis is an appropriate means to identify cardiac markers in studies of IPC and IR.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.2
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• pp.108-113
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• 2017

A sudden cardiac death (SCD) is defined as an unnatural sudden death caused by heart disease. To determine the cause of death, observation of the microscopic change in cardiac muscle tissue is suggested, rather than visual postmortem examination. However, this suggestion is time consuming to be applied in the field, is cost-ineffective, and is inconvenient. Therefore, the purpose of this study is to understand whether temporary inspection used to examine the cardiac marker (Myoglobin, CK-MB, cTn I) in postmortem blood via rapid cardiac triple test kit (which is used by clinics to diagnose patients with acute myocardial infarction) can effectively be utilized for the paragnosis of sudden, unnatural cardiac death. The results of postmortem examination and temporary investigation found that 23 groups (76.7%), among the 30 experimental groups, were assumed to be non-traumatic sudden cardiac deaths, which indicated a positive response (according to comparison with forensic autopsy); 4 groups, among the 10 control groups, were assumed to be cerebrovascular disease, which indicated a negative response; 1 group was assumed to be alcoholic and drug poisoning, indicating a positive response; and 1 group was assumed to be oxygen deficiency due to suffocation, indicating a positive response. Hence, it was found that the level of sensitivity and specificity of cardiac marker's temporary inspection showed significant result, 76.7% and 80% respectively. Given this, temporary inspection can be effectively used for the paragnosis of sudden cardiac death when the medical history, situation of the site, and postmortem interval are considered together. With the result of precedent research on time of first revelation and extinction in blood, and difference in concentration over time progress according to the characteristic of cardiac marker's (myoglobin, CK-MB, cTn I) individual material, further research on concentration of cardiac marker per each post time needs to be conducted in order to estimate time science death (which is required to identify the cause of death and investigation).

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.1.1-1.10
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• 2018

Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair.

• Molecules and Cells
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• v.37 no.4
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• pp.330-336
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• 2014

Thymosin beta4 (TB4) has multiple functions in cellular response in processes as diverse as embryonic organ development and the pathogeneses of disease, especially those associated with cardiac coronary vessels. However, the specific roles played by TB4 during heart valve development in vertebrates are largely unknown. Here, we identified a novel function of TB4 in endothelial-mesenchymal transformation (EMT) in cardiac valve endocardial cushions in zebrafish. The expressions of thymosin family members in developing zebrafish embryos were determined by whole mount in situ hybridization. Of the thymosin family members only zTB4 was expressed in the developing heart region. Cardiac valve development at 48 h post fertilization was defected in zebrafish TB4 (zTB4) morpholino-injected embryos (morphants). In zTB4 morphants, abnormal linear heart tube development was observed. The expressions of bone morphogenetic protein (BMP) 4, notch1b, and hyaluronic acid synthase (HAS) 2 genes were also markedly reduced in atrio-ventricular canal (AVC). Endocardial cells in the AVC region were stained with anti-Zn5 antibody reactive against Dm-grasp (an EMT marker) to observe EMT in developing cardiac valves in zTB4 morphants. EMT marker expression in valve endothelial cells was confirmed after transfection with TB4 siRNA in the presence of transforming growth factor ${\beta}$ ($TGF{\beta}$) by RT-PCR and immunofluorescent assay. Zn5-positive endocardial AVC cells were not observed in zTB4 morphants, and knockdown of TB4 suppressed TGF-${\beta}$-induced EMT in ovine valve endothelial cells. Taken together, our results demonstrate that TB4 plays a pivotal role in cardiac valve formation by increasing EMT.

• Journal of Life Science
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• v.20 no.10
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• pp.1458-1467
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• 2010

The present study was retrospectively designed to define whether preoperative levels of leukocytes and D-dimer are potentially useful factors in predicting perioperative outcomes of coronary heart disease (CHD). There was no relationship between preoperative leukocyte counts (Pre-OP leukocyte) and preoperative D-dimer levels (Pre-OP D-dimer). Pre-OP leukocyte counts each had positive correlation with cardiac troponin-I, creatine kinase-MB or C-reactive protein (cardiac markers) levels at preoperative and postoperative periods. Pre-OP D-dimer levels were positively associated with each cardiac marker at the same periods. Pre-OP leukocyte counts positively related with aspartate aminotransferase and alanine aminotransferase (liver markers), whereas Pre-OP D-dimer level positively or negatively correlated with bilirubin (liver marker), creatinine (renal marker) or glucose levels at preoperative and/or postoperative periods. Pre-OP leukocyte and Pre-OP D-dimer were inversely associated with Pre-OP high density lipoprotein cholesterol levels or left ventricular ejection fraction. Pre-OP leukocyte counts each had positive correlation operation duration and postoperative mechanical ventilation-time (PMVT), whereas Pre-OP D-dimer levels had positive relationship with PMVT, intensive care unit-staying period and hospitalization. The retrospective data suggest that Pre-OP leukocyte and Pre-OP D-dimer levels may be clinically useful factors for predicting perioperative outcomes in patients with CHD.

• Clinical and Experimental Pediatrics
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• v.63 no.4
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• pp.151-156
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• 2020

Background: Acute kidney injury (AKI) is one of the most significant postoperative complications of pediatric cardiac surgery. Because serum creatinine has limitations as a diagnostic marker of AKI, new biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) are being evaluated to overcome these limitations and detect AKI at an early stage after cardiac surgery. Purpose: This study aimed to investigate the clinical usefulness of these biomarkers in young children. Methods: Thirty patients with congenital heart diseases who underwent cardiac surgery using cardiopulmonary bypass (CPB) were selected, and their urine and blood samples were collected at baseline and 6, 24, and 48 hours after surgery. Serum creatinine and blood urea nitrogen levels as well as NGAL, KIM-1, and IL-18 levels in urine samples were measured, and clinical parameters were evaluated. Results: Of the 30 patients, 12 developed AKI within 48 hours after cardiac surgery. In the AKI group, 8 of 12 (66.6%) met AKI criteria after 24 hours, and urine KIM-1/creatinine (Cr) level (with adjustment of urine creatinine) peaked at 24 hours with significant difference from baseline level. Additionally, urine KIM-1/Cr level in the AKI group was significantly higher than in the non-AKI group at 6 hours. However, urine NGAL/Cr and IL-18/Cr levels showed no specific trend with time for 48 hours after cardiac surgery. Conclusion: It is suggested that urine KIM-1/Cr concentration could be considered a good biomarker for early AKI prediction after open cardiac surgery using CPB in young children with congenital heart diseases.

• Journal of Yeungnam Medical Science
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• v.18 no.1
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• pp.13-29
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• 2001

The enzyme activities of creatine kinase (CK), its isoenzyme MB (CK-MB) and of lactate dehydrogenase isoenzyme 1 (LD-1) have been used for years in diagnosing patients with chest pain in order to differentiate patients with acute myocardial infarction (AMI) from non-AMI patients. These methods are easy to perform as automated analyses, but they are not specific for cardiac muscle damage. During the early 90's the situation changed. First, creatine kinase ME mass (CK-MB mass) replaced the measurement of CK-MB activity. Subsequently cardiac-specific proteins, troponin T (cTnT) and troponin I (cTnI) appeared and displacing LD-1 analysis. However, troponin concentrations in blood increase only from four to six hours after onset of chest pain. Therefore a rapid marker such as myoglobin, fatty acid binding protein or glycogen phosphorylase BB could be used in early diagnosis of AMI. On the other hand, CK-MB isoforms alone may also be useful in rapid diagnosis of cardiac muscle damage. Myoglobin, CK-MB mass, cTnT and cTnI are nowadays widely used in diagnosing patients with acute chest pain. Myoglobin is not cardiac-specific and therefore requires supplementation with some other analyses such as troponins to support the myoglobin value. Troponins are very highly cardiac-specific. Only the sera of some patients with severe renal failure, which requires hemodialysis, have elevated cTnT and/or cTnI without there being any evidence of cardiac damage. The latest studies have shown that elevated troponin levels in sera of hemodialysis patients point to an increased risk of future cardiac events in a similar manner to the elevated troponin values in sera of patients with unstable angina pectoris. In addition, the bedside tests for cTnT and cTnI alone- or together with myoglobin and CK-ME mass can be used instead of quantitative analyses in the diagnosis of patients with chest pain. These rapid tests are easy to perform and they do not require expensive instrumentation. For the diagnosis of patient with chest pain, routinely myoglobin and CK-ME mass measurements should be performed whenever they are requested (24 h/day) and cTnT or cTnI on admission to the hospital and then 4-6 and 12 hours later and maintained less than 10% in imprecision.

• Journal of Chest Surgery
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• v.35 no.1
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• pp.27-35
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• 2002

Background: A perioperative myocardial infarction(PMI) is one of the major complications after CABG. Among diagnostic methods of PMI, CK-MB activity assays have been increasingly replaced by CK-MB mass assays, which have more sensitive, simple measurement. Also, new cardiac-specific and -sensitive marker, cardiac troponin I(cTnl), has been shown to be a marker of myocardial infarction. We report our evaluation of clinical significance of CK-MB mass and cTnl as a marker of PMI after CABG. Material and Method: We studied 32 patients who underwent CABG at Kangdong Sacred Hospital between April 2000 and April 2001. Postoperative serum CK-MB activity level, serum CK-MB mass, cTnl, electrocardiogram, echocardiogram, and clinical data were recorded prospectively The diagnosis of PMI was defined as positive 2 among 3 or all of the following , by a new Q wave on the electrocardiogram, by serum CK-MB activity higher than 200 lU/L within 72 hours after operation, and by new regional wall motion abnormality on the echocardiogram. Result: After CABG, 3 patients had sustained a PMI according to current diagnostic criteria. As serum CK-MB activity time course, a level of CK-MB activity 12 hours after CABG had very linear correlated significance with serum CK-MB mass 24hours(R=0.946) and cTnl 48 hours(R=0.933) after CABG(p=0.000). As we used a receiver operating characteristics curve(ROC curve) for a diagnostic cutoff value in patients with PMI, serum CK-MB mass levels higher than 30.05 ug/L 24 hours after CABG detected the presence of PMI with an area under the ROC curve of 1.0, a sensitivity of 100%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 100%. Also serum cTnl levels higher than 17.15 ug/L 48 hours after CABG detected the presence of PMI with an area under the ROC curve of 0.98, a sensitivity of 100%, a specificity of 96.6%, a positive preclictive value of 75%, and a negative predictive value of 100% Conclusion: We concluded that both the measurement of CK-MB mass and cTnl are the easier, accurate methods as a diagnostic marker of PMT after CABG, also as a proposal of diagnostic cutoff value enables to an early detection of PMI. However, a 1arger number of patient will be needed because of statistic limitation that a small number of participating patients, a small number of PMI.

• Journal of Chest Surgery
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• v.44 no.1
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• pp.44-50
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• 2011

Background: Cardiovascular complications are major causes of morbidity and mortality following non-cardiac thoracic operations. Recent studies have demonstrated that elevation of N-Terminal Pro-B-type natriuretic peptide (NT-proBNP) levels can predict cardiac complications following non-cardiac major surgery as well as cardiac surgery. However, there is little information on the correlation between lung resection surgery and NT-proBNP levels. We evaluated the role of NT-proBNP as a potential marker for the risk stratification of cardiac complications following lung resection surgery. Material and Methods: Prospectively collected data of 98 patients, who underwent elective lung resection from August 2007 to February 2008, were analyzed. Postoperative adverse cardiac events were categorized as myocardial injury, ECG evidence of ischemia or arrhythmia, heart failure, or cardiac death. Results: Postoperative cardiac complications were documented in 9 patients (9/98, 9.2%): Atrial fibrillation in 3, ECG-evidenced ischemia in 2 and heart failure in 4. Preoperative median NT-proBNP levels was significantly higher in patients who developed postoperative cardiac complications than in the rest (200.2 ng/L versus 45.0 ng/L, p=0.009). NT-proBNP levels predicted adverse cardiac events with an area under the receiver operating characteristic curve of 0.76 [95% confidence interval (CI) 0.545~0.988, p=0.01]. A preoperative NT-proBNP value of 160 ng/L was found to be the best cut-off value for detecting postoperative cardiac complication with a positive predictive value of 0.857 and a negative predictive value of 0.978. Other factors related to cardiac complications by univariate analysis were a higher American Society of Anesthesiologists grade, a higher NYHA functional class and a history of hypertension. In multivariate analysis, however, high preoperative NT-proBNP level (>160 ng/L) only remained significant. Conclusion: An elevated preoperative NT-proBNP level is identified as an independent predictor of cardiac complications following lung resection surgery.