• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.4
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• pp.672-678
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• 2002

Oxidative stress contributes to cellular injury following clinical and experimental ischemia/reperfusion scenarios. Oxidative injury can induce cellular and nuclear damages that result in apoptotic cell death. We tested the hypothesis that the catechin flavonoid of (-)epigallocatechin gallate, a green tea polyphenol, inhibits hydrogen peroxide ($H_2O$$_2$)-induced apoptosis in human umbilical vein endothelial cells. The effect of apigenin, a flavone found in citrus fruits, on apoptosis parameters was also examined. A 30 min pulse treatment with 0.25 mM $H_2O$$_2$ decreased endothelial cell viability within 24 hrs by > 30% ; this was associated with nuclear condensation and biochemical DNA damage consistent with programmed cell death. In the 0.25 mM $H_2O$$_2$apoptosis model, 50${\mu}{\textrm}{m}$ (-)epigallocatechin gallate markedly increased cell viability with a reduction in the nuclear condensation and DNA fragmentation. In contrast, equimicromolar apigenin increased cell loss with intense DNA laddering, positive nick-end labeling and Hoechst 33258 staining. Thus, polyphenolic (-)epigallocatechin gallate, but not apigenin flavone, qualify as an antioxidant in apoptosis models caused by oxidative stress. Further work is necessary for elucidating the anti-apoptotic mechanisms of polyphenolic catechins.

• Journal of Chest Surgery
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• v.48 no.3
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• pp.164-173
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• 2015

Background: Hypertrophied myocardium is especially vulnerable to ischemic injury. This study aimed to compare the early and late clinical outcomes of three different methods of myocardial protection in patients with aortic stenosis. Methods: This retrospective study included 225 consecutive patients (mean age, 65{\pm}10 years; 123 males) with severe aortic stenosis who underwent aortic valve replacement. Patients were excluded if they had coronary artery disease, an ejection fraction <50%, more than mild aortic regurgitation, or endocarditis. The patients were divided into three groups: group A, which was treated with antegrade and retrograde cold blood cardioplegia; group B, which was treated with antegrade crystalloid cardioplegia using histidine-tryptophan-ketoglutarate (HTK) solution; and group C, treated with retrograde cold blood cardioplegia. Results: Group A contained 70 patients (31.1%), group B contained 74 patients (32.9%), and group C contained 81 patients (36%). The three groups showed significant differences with regard to the proportion of patients with a New York Heart Association functional classification ${\geq}III$ (p=0.035), N-terminal pro-brain natriuretic peptide levels (p=0.042), ejection fraction (p=0.035), left ventricular dimensions (p<0.001), left ventricular mass index (p<0.001), and right ventricular systolic pressure (p <0.001). Differences in cardiopulmonary bypass time (p=0.532) and aortic cross-clamp time (p=0.48) among the three groups were not statistically significant. During postoperative recovery, no significant differences were found regarding the use of inotropes (p=0.328), mechanical support (n=0), arrhythmias (atrial fibrillation, p=0.347; non-sustained ventricular tachycardia, p=0.1), and ventilator support time (p=0.162). No operative mortality occurred. Similarly, no significant differences were found in long-term outcomes. Conclusion: Although the three groups showed some significant differences with regard to patient characteristics, both antegrade crystalloid cardioplegia with HTK solution and retrograde cold blood cardioplegia led to early and late clinical results similar to those achieved with combined antegrade and retrograde cold blood cardioplegia.

• Journal of Oriental Physiology
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• v.14 no.2 s.20
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• pp.179-187
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• 1999

To investigate how Jagamchotang provent cellular injury by a certain starting point on reperfusion injury after ischemia in myocardial cell, conducted MTT assay, LM stydy and measured LDH secretion, heart rate and nitric oxide(NO), and got the following results. 1. Jagamchotang did not injure cells even in $20{\mu}g/ml$. 2. Jaganchotang repressed the toxicity of mitochondria and cell membrane in reperfusing after ischemia and repressed the contraction of promontory of myocardial cell and reduction of the number of cells. Also maintained regular heart rate and reduced the number of heart rate. 3. Synthesis of NO by Jagamchotang in ischemia increased 1.9 times than a control. 4. When reperfusing with sodium nitropruside (SNO), NO donor in ischemia repressed the toxicity of mitochondria as the case of reperfusing with Jagamchotang in ischemia. Therefore, putting these findings together, it. can be said the effect of Jagamchotang in ischemia will be closely related with generation of NO.

• Journal of Ginseng Research
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• v.48 no.4
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• pp.395-404
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• 2024

Background: Ginsenoside Rg₁ (Rg₁) is one of the main active components in Chinese medicines, Panax ginseng and Panax notoginseng. Research has shown that Rg₁ has a protective effect on the cardiovascular system, including anti-myocardial ischemia-reperfusion injury, anti-apoptosis, and promotion of myocardial angiogenesis, suggesting it a potential cardiovascular agent. However, the protective mechanism involved is still not fully understood. Methods: Based on network pharmacology, ligand-based protein docking, proteomics, Western blot, protein recombination and spectroscopic analysis (UV-Vis and fluorescence spectra) techniques, potential targets and pathways for Rg₁ against myocardial ischemia (MI) were screened and explored. Results: An important target set containing 19 proteins was constructed. Two target proteins with more favorable binding activity for Rg₁ against MI were further identified by molecular docking, including mitogen-activated protein kinase 1 (MAPK1) and adenosine kinase (ADK). Meanwhile, Rg₁ intervention on H9c2 cells injured by H₂O₂ showed an inhibitory oxidative phosphorylation (OXPHOS) pathway. The inhibition of Rg₁ on MAPK1 and OXPHOS pathway was confirmed by Western blot assay. By protein recombination and spectroscopic analysis, the binding reaction between ADK and Rg₁ was also evaluated. Conclusion: Rg₁ can effectively alleviate cardiomyocytes oxidative stress injury via targeting MAPK1 and ADK, and inhibiting oxidative phosphorylation (OXPHOS) pathway. The present study provides scientific basis for the clinical application of the natural active ingredient, Rg₁, and also gives rise to a methodological reference to the searching of action targets and pathways of other natural active ingredients.

• Journal of Chest Surgery
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• v.34 no.7
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• pp.524-533
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• 2001

Background: Hyperoxemic cardiopulmonary bypass (CPB) has been recognized as a safe technique and is widely used in cardiac surgery. However, hyperoxemic CPB may produce higher toxic oxygen species and cause more severe oxidative stress and ischemia/reperfusion injury than normoxemic CPB. This study was undertaken to compare inflammatory responses and myocardial injury between normoxemic and hyperoxemic CPB and to examine the beneficial effect of normoxemic CPB. Material and method: Thirty adult patients scheduled for elective cardiac surgery were randomly divided into normoxic group (n=15), who received normoxemic CPB (about Pa $O_{2}$ 120 mmHg), and hyperoxic group (n=15), who received hyperoxemic CPB (about Pa $O_{2}$ 400 mmHg). Myeloperoxidase (MPO), malondialdehyde (MDA), adenosine monophosphate (AMP), and troponin-T (TnT) concentrations in coronary sinus blood were determined at pre- and post-CPB. Total leukocyte and neutrophil counts in arterial blood were measured at the before, during, and after CPB. Lactate concentration in mixed venous blood was analyzed during CPB, and cardiac index (Cl) and pulmonary vascular

• Clinical and Experimental Pediatrics
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• v.49 no.3
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• pp.317-325
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• 2006

Purpose : This study was carried out to elucidate the effects of nitric oxide synthase(NOS) inhibitor, NG-monomethyl-L-arginine(L-NMMA) and nitric oxide precursor, L-arginine(L-Arg) on cerebral hemodynamics and energy metabolism during reoxygenation-reperfusion(RR) after hypoxia-ischemia(HI) in newborn piglets. Methods : Twenty-eight newborn piglets were divided into 4 groups; Sham normal control(NC), experimental control(EC), L-NMMA(HI & RR with L-NMMA), and L-Arg(HI & RR with L-Arg) groups. HI was induced by occlusion of bilateral common carotid arteries and simultaneously breathing with 8 percent oxygen for 30 mins, and followed RR by release of carotid occlusion and normoxic ventilation for one hour. All groups were monitored with cerebral hemodynamics and cytochrome $aa_3$ (Cyt $aa_3$) using near infrared spectroscopy(NIRS). $Na^+$, $K^+$-ATPase activity, lipid peroxidation products, and tissue high energy phosphate levels were determined biochemically in the cerebral cortex. Results : In experimental groups, mean arterial blood pressure, $PaO_2$, and pH decreased, and base excess and blood lactate level increased after HI compared to NC group(P<0.05). These variables subsequently returned to baseline after RR except pH. There were no differences among the experimental groups. In NIRS, oxidized hemoglobin($HbO_2$) decreased and hemoglobin(Hb) increased during HI(P<0.05) but returned to base line immediately after RR; 40 min after RR, the $HbO_2$ had decreased significantly compared to NC group(P<0.05). Changes of Cyt $aa_3$ decreased significantly compared to NC after HI and recovered at the end of the experiment. Significantly reduced cerebral cortical cell membrane $Na^+$, $K^+$-ATPase activity and increased lipid peroxidation products(P<0.05) were not improved with L-NMMA or L-Arg. Conclusion : These findings suggest that NO is not involved in the mechanism of HI and RR brain damage during the early acute phase of RR.

• Clinical and Experimental Pediatrics
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• v.51 no.10
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• pp.1112-1117
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• 2008

Purpose : We intended to observe cell death and apoptotic changes in neurons in organotypic hippocampal slice cultures following oxygen-glucose deprivation (OGD), using propidium iodide (PI) uptake, Fluoro-Jade (FJ) staining, TUNEL staining and immunofluorescent staining for caspase-3. Methods : The hippocampus of 7-day-old rats was cut into $350{\mu}m$ slices. The slices were cultured for 10 d (date in vitro, DIV 10) and and exposed to OGD for 60 min at DIV 10. They were then incubated for reperfusion under normoxic conditions for an additional 48 h. Fluorescence of PI uptake was observed at predetermined intervals, and the cell death percentage was recorded. At 24 h following OGD, the slices were Cryo-cut into $15{\mu}m$ thicknesses, and Fluoro-Jade staining, TUNEL staining, and immunofluorescence staining for caspase-3 were performed. Results : 1) PI uptake was restricted to the pyramidal cell layer and DG in the slices after OGD. The fluorescent intensities of PI increased from 6 to 48 h during the reperfusion stage. The cell death percentage significantly increased time-dependently in CA1 and DG following OGD (P<0.05). 2) At 24 h after OGD, many FJ positive cells were detected in CA1 and DG. Some neurons had distinct nuclei and processes while others had fragmented nuclei and disrupted processes in CA1. TUNEL and immunofluorescent staining for caspase-3 showed increased expression of TUNEL labeling and caspase-3 in CA1 and DG at 24 h after OGD. Conclusion : The numerous dead cells in the slice cultures after OGD tended to display apoptotic changes mediated by the activation of caspase-3.

• Journal of Chest Surgery
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• v.30 no.2
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• pp.119-124
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• 1997

Using isolated rat heart preparations, we observed the protective effe ts of verapamil cardioplegia on ischemic myocardial injury. Isolated rat hearts were subjected to global ischemia at $25^{\circ}C$ Twenty four isolated Sprague Dawley rat hearts underwent 30 minutes of the retrograde nonworking perfusion with Krebs-Henseleit buffer solution followed by $25^{\circ}C$ cardioplegic solution (St. Thomas'Hospital Cardioplegic Solution) for 60 minutes. Before ischemic arrest, rat hearts were treated with cold cardioplegic solution in control group (n=12) and cold cardioplegic solution with verapamil (1 mg/L) in experimental group (n=12). After 60 minutes of ischemia, hemodynamic and biochemical parameters such as heart rate, left ventricular pressure (LVP), + dp/dt max, coronary flow and creatine phosphokinase (CPK) were measured before giving cardioplegia and 30 minutes after reperfusion. Verapamil group exhibited greater recovery of heart rate, LVP, +dpldt max, coronary flow and CPK than control group (p < 0.05).

• Journal of Chest Surgery
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• v.34 no.3
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• pp.212-223
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• 2001

배경: 이식폐의 보존 및 재관류 동안 cyclic adenosine monophosphate(cAMP)와 nitric oxide(NO)는 폐혈관 내 순환조절을 유지하는데 있어 중심적인 역할을 한다. 그러나 내치세포내의 cAMP와 NO 모두 허혈-재관류 과정 동안에 현저하게 감소한다. 이에 저자는 low potassium dextran(LPD) 폐조본액에 cAMP의 유사체인 dibutyry1 cAMP(db-cAMP)와 NO의 공여물질인 nitroglycerin(NTG)을 첨가하여 이들의 폐보존 효과를 알아보고, 이들은 첨가한 폐보존액 들의 효과를 비교하였다. 대상 및 방법: 토끼 폐장 분리관류 모형에 실험군은 각각 6마리씩 4개군으로 단순 LPD 페보존액만 사용한 경우(I군), LPD 용액에 NTG 만 참가한 경우(II군), cAMP 만 첨가한 겨우(III군) 그리고 두가지 모두를 첨가한 경우는 IV군으로 분류하였으며, 폐보존액이 주입된 심폐블록은 영상 1$0^{\circ}C$에서 24시간 동안 보관한 다음 100% 산소농도에서 기계호흡을 하면서 신선 정맥혈로 30분 동안 재관류를 시행하였다. 재관류폐의 평가를 위해 폐기능 및 폐부종 정도를 정량 측정하였으며, 유출로 혈액으로부터 tumor necrosis factor $\alpha$(TNF-$\alpha$)와 간접적인 NO의 총량을 알기 위해 nitrite/nitrate의 양을 측정하였다. 또한 재관류가 끝난 후 광학 및 전자현미경학적 소견을 관찰하였다. 결과: 모든 실험군 중 제 IV군 의 폐보존 능력이 가장 우수하였으나, 제 II, III, IV군 사이는 통RP적으로 유의한 차이가 없었다. 제 I군은 제 II, III, IV군들에 비해 유의하게 폐기능이 가장 나쁘고 폐부종 정도가 가장 심했다(p<0.05). 제 II군은 제 III군에 비해 더 좋은 폐기능을 보였고, 폐부종 정도가 덜 하였으나 통계적은 유의성은 없었다. TNF-$\alpha$ 는 제 IV 군이 Irns에 비해 유의하게 분비량이 적었다. (p<0.05). 총 NO의 양은 제 II군과 IV 군이 제 I 군과 III군보다 유의하게 높았으나(p<0.001), 제 II군과 IV군, 제 I군과 III군 사이 비교에서 유의한 차이는 없었다. 또한 제 I 군과 III군에서는 시간이 지남에 따라 유의하게 NO의 양이 점차 감소하였다. (p<0.05). 광학 및 전자현민경 소견상 폐포 및 폐혈관 구조가 제 II, III, IV 군이 I 군에 비해 더 잘 보존되어있었다. 결론: LPD 폐보존액에 db-cAMP 및 NTG의 첨가는 폐보존 효과가 모두 우수함을 확인하였고 이들의 폐보존 효과 차이는 거의 없음을 알수 있었다. 그렇지만 이들의 병합사용이 폐혈관 항상성을 더 잘 유지시킬 수 있고 허혈-재관류 손상을 줄여 폐보존 효과를 높일 수 있을 것이라고 기대된다.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.293-300
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• 2017

Prostaglandin $D_2$ ($PGD_2$) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of $PGD_2$ in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether $PGD_2$ can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. $PGD_2$ (0.1 to $10{\mu}M$) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of $PGD_2$ on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 ($1.0{\mu}M$) and AL-8810 ($1.0{\mu}M$), $PGD_2$ and prostaglandin $F2{\alpha}$ ($PGF2{\alpha}$) receptor antagonists, respectively. Moreover, $PGD_2$ clearly upregulated atrial peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and the $PGD_2$ metabolite 15-deoxy-${\Delta}12$, 14-$PGJ_2$ (15d-$PGJ_2$, $0.1{\mu}M$) dramatically increased atrial ANP secretion. Increased ANP secretions induced by $PGD_2$ and 15d-$PGJ_2$ were completely blocked by the $PPAR{\gamma}$ antagonist GW9662 ($0.1{\mu}M$). PD98059 ($10.0{\mu}M$) and LY294002 ($1.0{\mu}M$), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by $PGD_2$. These results indicated that $PGD_2$ stimulated atrial ANP secretion and promoted positive inotropy by activating $PPAR{\gamma}$ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating $PGD_2$-induced atrial ANP secretion.