• Journal of Ginseng Research
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• v.37 no.3
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• pp.283-292
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• 2013

Ginsenosides are divided into two groups based on the types of the panaxadiol group (e.g., ginsenoside-Rb1 and -Rc) and the panaxatriol group (e.g., ginsenoside-Rg1 and -Re). Among them, ginsenoside-Re (G-Re) is one of the compounds with the highest content in Panax ginseng and is responsible for pharmacological effects. However, it is not yet well reported if G-Re increases the hemodynamics functions on ischemia (30 min)/reperfusion (120 min) (I/R) induction. Therefore, in the present study, we investigated whether treatment of G-Re facilitated the recovery of hemodynamic parameters (heart rate, perfusion pressure, aortic flow, coronary flow, and cardiac output) and left ventricular developed pressure (${\pm}dp/dt_{max}$). This research is designed to study the effects of G-Re by studying electrocardiographic changes such as QRS interval, QT interval and R-R interval, and inflammatory marker such as tissue necrosis factor-${\alpha}$ (TNF-${\alpha}$) in heart tissue in I/R-induced heart. From the results, I/R induction gave a significant increase in QRS interval, QT interval and R-R interval, but showed decrease in all hemodynamic parameters. I/R induction resulted in increased TNF-${\alpha}$ level. Treatment of G-Re at 30 and $100{\mu}M$ doses before I/R induction significantly prevented the decrease in hemodynamic parameters, ameliorated the electrocardiographic abnormality, and inhibited TNF-${\alpha}$ level. In this study, G-Re at $100{\mu}M$ dose exerted more beneficial effects on cardiac function and preservation of myocardium in I/R injury than $30{\mu}M$. Collectively, these results indicate that G-Re has distinct cardioprotectective effects in I/R induced rat heart.

• Journal of radiological science and technology
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• v.24 no.2
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• pp.19-22
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• 2001

The purpose of this study is to evaluate time course of signal enhancement on Gadomer-17 enhance MRI, and to correlate the size of enhanced area with that of the infarct area on 2'3'5'-triphenyl tetrazolium chloride(TTC) histochemical examination for the assessment of myocardial viability in reperfused Myocardial Infarction in a cat model. Tan cats(average weight: 3.8 kg) which had undergone 90 minutes of occlusion of the LAD followed by 90 minutes of reperfusion underwent MR T2-weighted imaging, and T1-weighted imaging, enhanced T1-weighted imaging. We used 1.5T Magneton Vision MRI system(Siemens, Erlangen, Germany). Signal intensities were measured in the enhanced and non-enhanced areas of enhanced T1-weighted imaging. and TTC histochemical staining the size of the abnormal signal area on each image was compared with that of the infarct area. Maximum enhancement was detected during a $40{\sim}60$ minute period with an average enhancement of $168{\pm}9.9%$ of normal myocardium. TTC staining revealed that the size of the high signal area on T2-weighted images and of the enhanced area on enhanced T1-weighted images was greater than that of the infarct area($T2=48.1%{\pm}3.7$, enhanced $T1=47.2%{\pm}2.6$, TTC $staining=38.7%{\pm}3.1$ ; p<0.05). In reperfused Myocardial Infarction in a cat model, enhanced MR imaging delineates reversibly and irreversibly damaged myocardium, with a strong enhancement and a broad temporal window. We may therefore expect that enhanced MR image is useful for demonstrating myocardial injury.

• Journal of Chest Surgery
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• v.27 no.7
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• pp.563-570
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• 1994

Effect of ischemic preconditioning on left ventricular function after cardiac arrest in isolated rat heart.Ischemic preconditioning reduces infarct size caused by sustained ischemia. However, the effects of preconditioning on post ischemic cardiac function are not well-known. The objective of the present study was to determine whether preconditioning would improve the recovery of left ventricular functions after cardiac arrest in isolated rat heart model.Isolated rat hearts were allowed to equilibrate for 20 minutes and were then subjected to either 5 minutes of global, normothermic transient ischemia [Group 2 and 4] or not [Group 3]. A stabilization period of perfusion lasting 5 minutes after the termination of transient ischemia was followed by a standard global, normothermic 20 minute-ischemia and 35-minute reperfusion challenge [Group 3 and 4]. These following results were odtained.1. The recovery of left ventricular developed pressures showed no significant differences between Group 3 and Group 4 at 50 [P>0.3] and 85 minute [P>0.2].2. Heart rates showed no significant differences throughout all the course of experiment and between groups [P>0.5].3. The recovery of left ventricular maximum dP/dt showed no significant differences between Group 3 and Group 4 at 50 [P>0.1] and 85 minute [P>0.2].4. The recovery of pressure-rate products showed no significant differences between Group3 and Group 4 at 50 [P>0.5] and 85 minute [P>0.1].These results suggest that ischemic preconditioning does not provide significant benefit for the postischemic left ventricular functions in isolated rat hearts.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.7-12
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• 1990

Cyclobuxine D is a steroidal alkaloid, which was extracted from Buxus microphylla var. koreana Nakai. In our previous studies, we clarified several pharmacological actions of cyclobuxine D: an antiinflammatory action, hypotensive and bradycardiac effects, negative inotropic effects on the several smooth muscles and cardiac muscle. The present study was undertaken to elucidate possible mechanisms by protection of myocardial tells from ischemia and reperfusion induced derangement in cardiac function and metabolism by cyclobuxine D. For this purpose, the isolated rat heart was used. Rat hearts were perfused for 60 min under ischemia conditions in the presence and absence of cyclobuxine D and verapamil, and for 30 min under reperfusion conditions. Ischemia produced a marked decline in contractile force, an increase of resting tension, an immediate release of ATP metabolites and an accumulation of calcium in the left ventricle. Cyclobuxine D (100ng/ml) ameliorated the myocardial injury produced by ischemia.

• Journal of Microbiology and Biotechnology
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• v.31 no.8
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• pp.1069-1078
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• 2021

Sevoflurane postconditioning (SPostC) has been proved effective in cardioprotection against myocardial ischemia/reperfusion injury. It was also reported that heat shock protein 70 (HSP70) could be induced by sevoflurane, which played a crucial role in hypoxic/reoxygenation (HR) injury of cardiomyocytes. However, the mechanism by which sevoflurane protects cardiomyocytes via HSP70 is still not understood. Here, we aimed to investigate the related mechanisms of SPostC inducing HSP70 expression to reduce the HR injury of cardiomyocytes. After the HR cardiomyocytes model was established, the cells transfected with siRNA for HSP70 (siHSP70) or not were treated with sevoflurane during reoxygenation. The lactate dehydrogenase (LDH) level was detected by colorimetry while cell viability and apoptosis were detected by MTT and flow cytometry. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to detect HSP70, apoptosis-, cell cycle-associated factors, iNOS, and Cox-2 expressions. Enzyme-linked immuno sorbent assay (ELISA) was used to measure malondialdehyde (MDA) and superoxide dismutase (SOD). SPostC decreased apoptosis, cell injury, oxidative stress and inflammation and increased viability of HR-induced cardiomyocytes. In addition, SPostC downregulated Bax and cleaved caspase-3 levels, while SPostC upregulated Bcl-2, CDK-4, Cyclin D1, and HSP70 levels. SiHSP70 had the opposite effect that SPostC had on HR-induced cardiomyocytes. Moreover, siHSP70 further reversed the effect of SPostC on apoptosis, cell injury, oxidative stress, inflammation, viability and the expressions of HSP70, apoptosis-, and cell cycle-associated factors in HR-induced cardiomyocytes. In conclusion, this study demonstrates that SPostC can reduce the HR injury of cardiomyocytes by inducing HSP70 expression.

• Journal of Chest Surgery
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• v.22 no.6
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• pp.887-893
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• 1989

Donor availability is a major limiting factor in heart transplantation. Prolonging donor heart preservation would facilitate distant heart procurement. The setup used was the isolated retrograde perfused nonworking rabbit heart model and 4 hours of preservation at 2oC. And the electron microscopic findings of the myocardium were evaluated after reperfusion for 5 minutes. The following three groups [each group, n=4] were prepared: Group I: the heart was arrested with the St. Thomas Hospital solution [STH] and stored in Ringers lactate solution [RLS]; Group II: the heart was arrested with STH and stored in Modified Collins-Sachs solution [MCS]; Group g: the heart was arrested with and stored in MCS. The result was the most severe myocardial injury in the Group III on electron microscopic study.

• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.167-175
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• 2001

Recent studies have shown that cytokines are capable of modulating cardiovascular function and that some drugs used in the treatment of heart failure variably modulate the production of cytokines. Hige- namine, a positive inotropic isoquinoline alkaloid, has been used traditionally as cardiac stimulant, and reported to reduce nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression in LPS- and/or cytokine-activated cells in vitro and in vivo. Therefore, we investigated whether higenamine modulates the production of proinflammatory cytokines in myocardial infarction. In addition, effects of higenamine on antioxidant action and antioxidant enzyme expression (MnSOD) were studied. Myocardial infarction (MI) was confirmed by measuring left ventricular (LV) pressure after occlusion of the left anterior descending coronary artery (LAD) for 5 weeks in rats. Treatment of higenamine (10 mg/kg/day) reduced infarct size about 35 %, which accompanied by reduction of production TNF-$\alpha$, IL-6, but not IFN-${\gamma}$ and IL-1$\beta$ in the myocardium. The expression of TNF-$\alpha$ mRNA in infracted myocardium was significantly reduced by higenamine. Although iNOS mRNA was not detected, nitrotyrosine staining was significantly increased in myocardium of Ml compared to higenamine-treated one, Indicating that peroxynitrite-induced damage is evident in MI. Cytochrome c oxidation by peroxynitrite was concentration-dependently reduced by higenamine, an effect which was almost compatible to glutathion. Higenamine treatment did not affect the expression of MnSOD mRNA in myocardial tissues in MI. Taken together, higenamine may be beneficial in oxidative stress conditions such as ischemic-reperfusion injury and MI due to antioxidant action as well as modulation of cytokines.

• 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.3
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• pp.203-211
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• 2001

배경: AT$_1$수용체의 길항제가 세포 수준에서 심근을 재관류 손사으로부터 보호할수 있다는 것으로 알려져 있지만, 생체내에서의 효과나 그 기전은 아직 명확히 밝혀지지 않았다. 본 연구에서는 백서 심근 허혈 모델을 이용하여, AT$_1$ 수용체의 길항제들 중 하나인 irbesartan이 심근이 재관휴 손상에 미치는 효과를 알아보고, 재관류 손상을 매개하는 한 각지 기전으로서 세포자멸의 기여에 대하여 연구하고자 하였다. 대상 및 방법: Sprague-Dawley 백서에서 무작용 부형약(10% gum arabic: 1군, 개체수=14관) irbesartan(50mg/kg/day :II 군, 개체수=12)을 각각 3일 동안 24시간마다 경구로 투여하였다. 실험동물의 좌 관상 동맥을 45분간 결찰하였다가, 그 후 2시간 동안 재관류시킨 다음 심장을 적출 하였다. TTC(triphenyltetrazolium chloride) 염색법을 이용하여, 허혈 노출 부위에 대한 심근 경색 부위의 비율을 측정하였다. Agarose gel 전기영동상의 DNa 분절 양상과 TUNEL(TdT-mediated dUCP nick end labeling) 염색을 관찰하여 세포자멸이 일어난 정도를 평가하였다. 세포자멸을 조절하는데 관여하는 것으로 알려진 Bcl-2(B-cell lymphoma 2 gene), Bad 등의 단백과 ERK (extracellular signal-regulated kinase), p-38 등 신호전달체계에 작용하는 MAPKs(mitogen-activated protein kinases)의 발현을 측정하기 위하여 Western blot을 시행하였다. 결과: 허혈 노출부위에 대한 심근 경색부위의 비율은 II군(42$\pm$2.7%)이 I군( 64.1$\pm$4.65)에 비해 유의하게 작았다.(p< 0.05), Agarose gel 전기영동상의 DNA laddering 양상은 I군에서 보다 높게 발현되었다. Bad와 ERK2의 발현은 두 군간에 유의한 차이가 없었다. 결론: AT$_1$수용체 길항제인 irbesartan은 생체에서 심근의 재관류 손상을 줄이는 효과가 있었다. 이 효과는 적어도 부분적으로 나만 심근세포의 세포자멸이 감소한 것에 기인한 것으로 설명할 수 있으며, 이 항-세포 자멸 효과는 Bcl-2의 발현증가와 관련이 있는 것으로 추정되었다.

• Journal of Chest Surgery
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• v.29 no.2
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• pp.199-207
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• 1996

Ischemic myocardial damage is inevitable to cardiac surgery. Myocardial damage after initiation of reperfusion through the coronary arteries is one of the most important determinants of a successful surgery. Adenosine is a potent vasodilator, and is also known to induce rapid cardioplegic arrest by its property of antagonizing cardiac calcium channels and activating the potassium channel. Thus, we initiated this study with adenosine to improve postischemic recovery in the isolated rat heart. We tested the hypothesis that adenosine could be more effective than potassium in inducing rapid cardiac arrest and enhancing postischemlc hemodynamic recovery. Isolated rat hearts, connected to the Langendorff appratus, were perfused with Krebs-Henseleit buffer and all hearts were subjected to arrest for 60 minutes. Three groups of hearts were studied according to the composition of cardioplegic solutions : Group A (n=10), adenosine 10mmo1/L+potassium free modified St. Thomas cardioplegia : Group B (n=10), adenosine 400mo1/L+S1. Thomas cardioplegia:Group C(control, n=10), St. Thomas cardioplegia. Adenosine-treated groups (group A & B) resulted in more rapid cardiac arrest than control group (C) (p< 0.01). There was greater improvement in recovery of coronary blood flow at 20 and 30 minutes of reperfusion in group A and at 20 minutes in group B when compared with control group(p<0.01). Recovery of systolic blood pressure at 10 minutes after reperfusion in group A and B was significantly superior to that in group C (p<0.01). Recovery of dp/dt at 10 minute after reperfusion in group A was also significantly superior to group C (p<0.05). Group A and B showed better recovery rates than control group in aortic blood flow, cardiac output, and heart rate, but there were no statistical differences. CPK levels of coronary flow in group A were significantly low (p< 0.01). We concluded that adenosine-enriched cardioplegic solutions have better effects on rapid cardiac arrest and postischemic recovery when compared with potassium cardioplegia.