• Korean Circulation Journal
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• 제48권11호
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• pp.1014-1024
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• 2018

Background and Objectives: Intense exercise (IE) induced myocardial fibrosis (MF) showed contradictory findings in human studies, making the relationship between IE and the development of MF unclear. This study aims to demonstrate exercise induced MF is associated with cardiac damage, and inflammation is essential to the development of exercise induced MF. Methods: Sprague-Dawley rats were submitted to daily 60-minutes treadmill exercise sessions at vigorous or moderate intensity, with 8-, 12-, and 16-week durations; time-matched sedentary rats served as controls. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum cardiac troponin I (cTnI) concentration. After completion of the exercise protocol rats were euthanized. Biventricular morphology, ultrastructure, and collagen deposition were then examined. Protein expression of interleukin $(IL)-1{\beta}$ and monocyte chemotactic protein (MCP)-1 was evaluated in both ventricles. Results: After IE, right but not left ventricle (LV) MF occurred. Serum cTnI levels increased and right ventricular damage was observed at the ultrastructure level in rats that were subjected to long-term IE. Leukocyte infiltration into the right ventricle (RV) rather than LV was observed after long-term IE. Long-term IE also increased protein expression of proinflammation factors including $IL-1{\beta}$ and MCP-1 in the RV. Conclusions: Right ventricular damage induced by long-term IE is pathological and the following inflammatory response is essential to the development of exercise induced MF.

• 생명과학회지
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• 제20권10호
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• pp.1458-1467
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• 2010

이 연구는 관상동맥질환 수술기주위의 결과예측에 있어 수술 전 백혈구 및 D-dimer 수치가 유용한 인자가 될 수 있는지를 규명하기 위해 회고적으로 실시하였다. 수술 전 백혈구 수는 수술 전 및 후의 심장표지자인 troponin-I, creatine kinase-MB, C-반응단백 각각의 농도와 정의 상관성이 있었다. 수술 전 D-dimer 농도 역시 수술기주위의 심장표지자들과 정의 상관관계를 보였다. 수술 전 백혈구 수는 간표지자인 aspartate aminotransferase 및 alanine aminotransferase의 수술 전후 농도와 정의 상관관계를 보였는데 비해, 수술 전 D-dimer 농도는 수술 전후 빌리루빈 농도, 수술 전 글루코스 농도, 수술 후 크레아티닌 농도와 각각 정 또는 역의 상관관계가 있었다. 수술 전 백혈구 및 D-dimer 수치 둘 다 수술 전 고밀도콜레스테롤 농도 및 좌심실구출계수와 각각 역의 상관관계가 있었다. 수술전 백혈구 수는 수술시간 및 수술 후 기계보조 호흡시간과 각 정의 상관관계를 보였고, 수술 전 D-dimer 농도는 수술 후 기계보조 호흡시간, 중환자실 치료기간, 재원기간과 각 정의 상관관계가 있었다. 이 회고적 조사의 결과는 수술 전 백혈구 및 D-dimer 수치가 관상동맥수술 환자들의 수술기주위 결과예측에 있어 임상적으로 유용한 인자들이 될 수 있음을 시사하고 있다.

• Anatomy and Cell Biology
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• 제57권2호
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• pp.256-270
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• 2024

The antidepressant drug trazodone (TRZ) is commonly used for treating depression, anxiety, and insomnia, however, it causes cardiotoxicity, which is one of its limitations. The objective of this work was to investigate the impact of sage (Salvia officinalis) in rats against cardiotoxicity induced by TRZ and to investigate the mechanisms involved in its cardio-protective properties through autophagy and oxidative stress. Fifty male albino rats were split randomly into five experimental groups: control group, sage oil group (100 mg/kg), TRZ group (20 mg/kg), protective group, and curative group. Cardiac function biomarkers (aspartate aminotransferase [AST], creatine kinase-MB [CK-MB], and cardiac troponin T [cTnI]) were assessed in serum. Oxidative stress and inflammatory biomarkers in cardiac tissue (total antioxidant capacity, malondialdehyde, and tumor necrosis factor-α) were evaluated. Heart tissues were subjected to histological, immunohistochemical, and ultrastructural evaluations. DNA damage also evaluated. Significant rise in the levels of AST, CK-MB, and cTnI were observed with enhanced autophagy along with marked histopathological changes in the form of interrupted muscle fibers with wide interstitial spaces with areas of hemorrhage and extravasated blood and interstitial mononuclear cellular infiltration in TRZ group. DNA damage was also significantly increased in TRZ group. However, administration of sage in both protective and curative groups show marked improvement of the cardiac alterations. In conclusion, sage ameliorated the alterations in the heart induced by trazadone through modulation of autophagy and oxidative stress.

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.493-501
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• 2018

The present study was carried out with the hypothesis that combination of canagliflozin and omega-3 fatty acid may have potential effect on insulin level, insulin resistance, cardiac biomarkers, inflammatory cytokines and histological studies in type 2 diabetes mellitus (DM). Type 2 DM was induced by injecting nicotinamide (120 mg/kg, i.p.) 15 min before STZ (60 mg/kg) injection. Canagliflozin (5 and 10 mg/kg) and omega-3 fatty acid (300 mg/kg) were given for 28 days after confirmation of diabetes. Biochemical estimations revealed elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines in diabetic group. Daily dosing of alone canagliflozin and omega-3 fatty acid slightly reduced elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines ($IL-1{\beta}$, IL-2, and $TNF{\alpha}$), whereas canagliflozin and omega-3 fatty acid combination has reduced these biochemical parameters significantly when compared with diabetic group. Similarly in diabetic group the levels of cardiac biomarkers such as lipid profile, LDH, CKMB and troponin were significantly increased. Elevated levels of cardiac biomarkers were significantly reduced after daily dosing of alone canagliflozin and omega-3 fatty acid. Canagliflozin and omega-3 fatty acid combination has offered better improvement in cardiac biomarkers compared to alone canagliflozin and omega-3 fatty acid. Histopathological analysis also supported the above hypothesis that combination therapy (canagliflozin and omega-3 fatty acid) offered better protection against degenerative changes in ${\beta}-cells$ of pancreas as compared to alone treatment with these drugs. Thus the present study revealed that canagliflozin and omega-3 fatty acid can be used as potential combination therapy in type 2 DM along with cardiac complication.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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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.

• Clinical and Experimental Reproductive Medicine
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• 제29권2호
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• pp.139-147
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• 2002

Objective : This study was to establish a reproducible differentiation system from the parthenogenetic mouse embryonic stem (P-mES02) cells into functional cardiomyocytes like as in vitro fertilization mouse embryonic stem (mES01) cells. Materials and Methods: To induce differentiation, P-mES02 cells were dissociated and aggregated in suspension culture environment for embryoid body (EB) formation. For differentiation into cardiomyocytes, day 4 EBs were treated with 0.75% dimethyl sulfoxide (DMSO) for another 4 days (4-/4+) and then were plated onto gelatin-coated dish. Cultured cells were observed daily using an inverted light microscope to determine the day of contraction onset and total duration of continuous contractile activity for each contracting focus. This frequency was compared with the results of DMSO not treated P-mES02 group (4-/4-) and mES01 groups (4-/4+ or 4-/4-). For confirm the generation of cardiomyocytes, beating cell masses were treated with trypsin-EDTA, dispersed cells were plated onto glass coverslips and incubated for 48 h. Attached cells were fixed using 4% paraformaldehyde and incubated with specific antibodies (Abs) to detect cardiomyocytes (anti-sarcomeric ? -actinin Ab, 1 : 100; anti-cardiac troponin I Ab, 1 : 2000) for 1 h. And the cells were finally treated with FITC or TRITC labelled 2nd Abs, respectively, then they were examined under fluorescence microscopy. Results: Rhythmically contracting areas in mES01 or P-mES02 cells were firstly appeared at 9 or 10 days after EBs plating, respectively. The highest cumulative frequency of beating EBs was not different in both treatment groups (mES01 and P-mES02, 4-/4+) with the results of 61.3 % at 13 days and 69.8% at 15 days, respectively. Also, the contracting duration of individual beating EBs was different from minimal 7 days to maximal 53 days. However, DMSO not treated groups (mES01 and P-mES02, 4-/4-) also had contracting characteristics although their frequency was a few compared to those of DMSO treated groups (6.0% and 4.0%). Cells recovered from the spontaneously contracting areas within EBs in both treated groups were stained positively with muscle specific anti-sarcomeric ? -actinin Ab and cardiac specific anti-cardiac troponin I Ab. Conclusion: This study demonstrated that the P-mES02 cell-derived cardiomyocytes displayed similarly structural properties to mES01 cell-derived cardiomyocytes and that the DMSO treatment enhanced the cardiomyocytes differentiation in vitro.

• Journal of Chest Surgery
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• 제31권1호
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• pp.20-27
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• 1998

Troponin T(이하 TnT)는 주로 심근세포에 존재하며 심근손상 시에만 유리되는 심근특이 효소이다. 저자들은 개심술을 시행한 34명의 환자들을 대상으로 수술 전후 심근손상에 대한 지표로서 TnT의 유용성에 대해 조사하였다. 환자들은 허혈성 심질환에 의한 관동맥 우회술이 11례, 후천성 판막 질환이 13례, 그리고 선천성 심질환이 10례였다. 이들은 술후 흉통과 심전도의 ST분절과 T파의 변화 등에 의거하여 심근손상이 의심되는 환자들(A군, 11례)과 정상 소견을 가진 환자들(B군, 23례)로 구분하였다. TnT의 측정은 효소 면역법을 이용하여 술 전, 수술 직후와 술후 1, 2, 3, 7일에 각각 측정하여 수술 전후의 수치 변화를 각 군간에 서로 비교하였고, 같은 시기에 측정한 CK-MB의 변화와 비교 분석하였다. A군에서는 수술 직후와 술후 1, 2, 3, 7일에 각각 1.37$\pm$0.26 $\mu$g/L, 3.16$\pm$0.66 $\mu$g/L, 2.39$\pm$0.74 $\mu$g/L, 2.49$\pm$0.76 $\mu$g/L, 그리고 1.23$\pm$0.60 $\mu$g/L로 변화하였으며, B군에서는 0.38$\pm$0.04 $\mu$g/L, 0.34$\pm$0.05 $\mu$g/L, 0.25$\pm$0.03 $\mu$g/L, 0.24$\pm$0.04 $\mu$g/L, 그리고 0.11$\pm$0.03 $\mu$g/L로 두 군간에 전기간에 걸쳐서 유의한 차이를 가졌다(P<0.01). 이에 반하여 CK-MB는 술후 1일째만 A군과 B군간에 145.04$\pm$35.08 IU/L과 31.28$\pm$5.87 IU/L로 유의한 차이가 있었고(P<0.05), 2일째부터 급격히 감소하여 3일 이후에는 술전치로 환원하였다. 혈청 TnT치가 1.0 $\mu$g/L이상인 경우를 술후 심근손상의 기준으로 볼 때 TnT는 심근손상의 진단에 있어서 100%의 민감도와 87%의 특이도를 보였다(P<0.01). 따라서 TnT는 심근손상 환자에 있어서 CK-MB와 달리 수술 직후부터 증가하여 지속됨으로써 심근손상의 정도를 더욱 민감하게 반영하고, 장기간 유의한 차이를 보여줌으로써 술후의 심근손상을 진단하는데 있어서 기존의 방법들보다 더욱 유용한 것으로 사료된다.

• 한국자원식물학회지
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• 제25권6호
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• pp.693-699
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• 2012

This study was conducted to investigate the effects of Woohwangcheungsimweun (ox bezoar), deer antlers, and wild ginseng on induction of cardiomyocyte differentiation using the established mouse embryonic stem (ES) cells. The expression of atrial natriuretic peptide (ANP) was highest in Woohwangcheungsimweun treatment group. The expression of rabbit anti-GATA-4(GATA-4) and troponin (TnI) were highest in wild ginseng and Woohwangcheungsimweun treatment groups, respectively. Fluorescence activated cell sorting (FACS) analysis showed that the expression of ANP was highest in Dimethyl sulfoxide(DMSO) and Woohwangcheungsimweun treatment groups. The expression of GATA-4 was relatively high in wild ginseng treatment group. The expression of TnI was highest in Woohwangcheungsimweun treatment group. In the gene expression analysis, DMSO greatly inhibited GATA-4 expression to 25% of control. Woohwangcheungsimweun treatment caused to increase cTnI and cardiac ANP expression significantly. Wild ginseng extract upregulated GATA-4 gene expression. In conclusion, DMSO widely used as cardiomyocyte differentiation inducer did not show significant effects on the expression of ANP, GATA-4 and TnI in this study. Woohwangcheungsimweun showed upregulation of ANP and TnI expression. Wild ginseng extract showed greater effects than DMSO on GATA-4 expression. These results might suggest that the combination of Woohwangcheungsimweun and wild ginseng extract treatment can be expected to increase expressions of all three genes.

• 대한의생명과학회지
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• 제22권1호
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• pp.9-17
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• 2016

Unfortunately, the five-year survival rate of lung cancer is relatively low compared with other cancers. Therefore, better predictors are need for prognosis, therapeutic strategy, risk stratification and predicting long-term mortality of lung cancer. Recently, increasing data suggest that Glasgow Prognostic Score (GPS) and procalcitonin levels are useful predictor cancer prognosis. In this study, we retrospectively investigated the correlation of GPS or procalcitonin to clinical variables in patients with pretreatment lung cancer. In 135 patients with pretreatment lung cancer, GPS, procalcitonin, demographic characteristics, hematological, coagulation, biochemical, inflammatory and cardiac markers were measured. Monocyte, eosinophil, basophil, neutrophil to lymphocyte ratio, red cell distribution width (RDW), platelet to lymphocyte ratio, mean platelet volume to platecrit ratio, D-dimer and prothrombin time (PT) levels were higher, whereas mean platelet volume was lower than their normal ranges. Glucose and sodium levels were low, whereas gamma glutamyl transferase (GGT), total bilirubin, creatinine and inorganic phosphorus concentrations were increase compared their normal ranges. Procalcitonin, high sensitivity C-reactive protein and troponin-I concentrations were elevated compared with their normal ranges. GPS had significantly positive or negative relations to cancer stage, hematological, coagulation, biochemical, inflammatory and troponin-I. Based on the data, we suggest that GPS may be a potent and useful predictor for prognosis, therapeutic strategy, risk stratification and predicting long-term mortality of lung cancer.

• 대한의생명과학회지
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• 제16권4호
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• pp.247-258
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• 2010

The objective of this research was to evaluate the relationships of preoperative (Pre-OP) levels of hematological and biochemical indices to perioperative variables in patients that underwent coronary artery bypass graft surgery (CABG). Pre-OP levels of hematological factors [total white blood cells (T-WBC), erythrocytes, hemoglobin, hematocrit, glycohemoglobin A1c (HbA1c), or platelet] were negatively or positively related with biochemical indices [alanine aminotransferase (ALT), bilirubin, glucose, fructosamine, triglyceride, and high density lipoprotein cholesterol (HDL)]. Pre-OP levels of hematological factors and biochemical indices were negatively or positively correlated with echocardiographic variables. Pre-OP level of HbA1c had a relationship with C-reactive protein. Pre-OP levels of aspartate aminotransferase (AST), ALT, HDL, glucose, fructosamine, or blood urea nitrogen (BUN) were positively or negatively associated with Pre-OP levels of cardiac markers (brain natriuretic peptide, troponin-I, creatine kinase isoenzyme 2, or CRP). Pre-OP levels of hematological factors (excepting T-WBC) related with operation time (OPT), postoperative mechanical ventilation time (POMVT), intensive care unit-period (ICU-period) or hospitalization. Pre-OP levels of AST, ALT, bilirubin, triglyceride, HDL, low dwensity lipoprotein, fructosamine, or BUN were positively or negatively correlated with OPT, graft numbers, POMVT, ICU-period or hospitalization. Retrospective this study reveals that Pre-OP levels of hematological and biochemical markers are associated with echocardiographic variables, several cardiac markers and postoperative outcomes, suggesting that Pre-OP levels of hematological and biochemical markers may be useful predictors for the diagnosis and prognosis of coronary artery disease.