• Title/Summary/Keyword: Myocardial ischemia

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Myocardial Protection by Recombinant Soluble P-selectin Glyco-protein Ligand-1: Suppression of Neutrophil and Platelet Interaction Following Ischemia and Reperfusion

  • Ham, Sang-Soo;Jang, Yoon-Young;Song, Jin-Ho;Lee, Hyang-Mi;Kim, Kwang-Joon;Hong, Jun-Sik;Shin, Yong-Kyoo
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.6
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    • pp.515-523
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    • 2000
  • Polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia/reperfusion (MI/R) injury. Moreover, platelets are also important blood cells that can aggravate myocardial ischemic injury. This study was designed to test the effects of PMNs and platelets separately and together in provoking cardiac dysfunction in isolated perfused rat hearts following ischemia and reperfusion. Additional control rat hearts were perfused with $75{\times}10^6$ PMNs, with $75{\times}10^6$ platelets, or with $75{\times}10^6\;PMNs+75{\times}10^6$ platelets over a five minute perfusion followed by a 75 min observation period. No significant reduction in coronary flow (CF), left ventricular developed pressure (LVDP), or the first derivative of LVDP (dP/dt max) was observed at the end of the observation period in any non-ischemic group. Similarly, global ischemia (I) for 20 min followed by 45 minutes of reperfusion (R) produced no sustained effects on the final recovery of any of these parameters in any group of hearts perfused in the absence of blood cells. However, I/R hearts perfused with either PMNs or platelets alone exhibited decreases in these variables of $5{\sim}10%$ (p<0.05 from control). Furthermore, I/R hearts perfused with both PMNs and platelets exhibited decreases of 50 to 60% in all measurements of cardiac function (p<0.01). These dual cell perfused I/R hearts also exhibited marked increases in cardiac myeloperoxidase (MPO) activity indicating a significant PMN infiltration, and enhanced P-selectin expression on the coronary microvascular endothelium. All cardiaodynamic effects as well as PMN accumulation and P-selectin expression were markedly attenuated by a recombinant soluble PSGL-1 which inhibits selectin mediated cell adhesion. These results provide evidence that platelets and PMNs act synergistically in provoking post-reperfusion cardiac dysfunction, and that this may be largely due to cell to cell interactions mediated by P-selectin. These results also demonstrate that a recombinant soluble PSGL-1 reduces myocardial reperfusion injury by platelet and PMNs interaction.

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Factors Related to the Development of Myocardial Ischemia During Mechanical Ventilation (인공 호흡기 적용에 따른 심근 허혈의 발생에 관한 연구)

  • Kim, Tae-Hyung;Kim, You-Ho;Lim, Chae-Man;Kim, Won;Shim, Tae-Sun;Lee, Sang-Do;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong;Koh, Youn-Suck
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.5
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    • pp.645-653
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    • 1999
  • Introduction : Although myocardial ischemia tends to occur more frequently than can he documented in ventilated patients, it has not been well studied on the factors related to the occurrence of the ischemia. Methods : To investigate the related factors to ischemia development, a prospective study was done in 95 cases with consecutive 73 patients who had received mechanical ventilation(MV) in MICU. In addition to 24 h holter monitoring, echocardiogram, electrolytes, cardiac enzymes, hemodynamic, and gas exchange measurements were done within 24 h after initiation of MV in 69 cases. The measurements were repeated at weaning period in 26 cases. The ischemia was defined by the ST segment changes; up-sloping depression more than 1.5 mm or down-sloping or horizontal depression more than 1.0 mm from isoelectric baseline for 80 ms following J point. Results : Twelve patients(12.6% in 95 cases) developed ischemia in total. The incidence of ischemia development showed an increased tendency in the initial 24 hr after MV (15.9%) and in patients with left-sided heart failure found by echocardiogram (18.2%) compared with that of the weaning period (3.8%) and patients without heart failure (10.9%) (P=0.12, P=0.09, in each). There were no differences in APACHE III score, baseline ECG findings, electrolytes abnormalities, use of inotropics or bronchodilators, presence of sepsis or shock, mode of ventilation, and survival rate according to the development of ischemia. Maximal heart rates and mean arterial pressure also were not different between patients with ($137.2{\pm}30.9/min$, $82.5{\pm}15.9$ mm Hg) and without ischemia ($l29.5{\pm}29.7/min$, $83.8{\pm}17.6$ mm Hg). Conclusion : Although the incidence of myocardial ischemia was 12.6% in total, there were no clinically predictable factors to the development of ischemia during mechanical ventilation.

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Integration of virtual screening and proteomics reveals potential targets and pathways for ginsenoside Rg1 against myocardial ischemia

  • Rongfang Xie;Chenlu Li;Chenhui Zhong;Zuan Lin;Shaoguang Li;Bing Chen;Youjia Wu;Fen Hu;Peiying Shi;Hong Yao
    • 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.

Pre-and Post-ishemic Changes of the Constituent Enzymes in Isolated Rabbit's Myocardium (허혈전후 적출 가토 심근내의 구성 효소의 변화)

  • 천수봉;전도환;이재성;김송명
    • Journal of Chest Surgery
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    • v.33 no.2
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    • pp.117-124
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    • 2000
  • Background: Nucleoside transport inhibitor(NTI) Keeps AMP, ADP, ATP levels high in myocytes by inhibiting adenosine cataboilsm so that it may preserve the myocardial contractability during ischemia In this study we investigated the effects of cyclic AMP phosphodiesterase inhibor(C-AMP PDSI) and S-P-nitrobenzyl-6 -thioniosine(NBT; a sort of NIT) on myocadial preservation and changes of constituent enzyme. Material and method: Twenty-six isolated rabbit hearts were perfused with Krebs-Henseleit buffer solution for 20 minutes arrested for 20 minutes and ten reperfused for 30 minutes. The following four groups were prepared and hemodynamic changes coronary effluent lactate dehydrogenase (LDH) a-hydroxybutylic accid(a-HBD) levels and myocardial LDH creatine kinase-MB (CK-MB) adenosine deaminase(ADA) a-HBD levels and myocardial LDH creatine kinase-MB (CK-MB) adenosine deaminase(ADA) a-HBD levels were analysed before and after cardiac arest ; Group I(control) ; the heart was only perfused with K-H ; Group II ; the heart was perfused with K-H including C-AMP PDSI(Amrinone 25mg/L); Group III ; the heart was perfused with K-H including NBT(4.19mg/L) ; Group IV ; the heart was perfused with K-H including C-AMP PDSI + NBT. Result : Left venticular developed pressure(LVDP) at 10 minutes of the equilibrium was significantly higher in group III(72.1$\pm$5.3 mmHg p<0.01) and group III(72$\pm$5.6 mmHg P<0.025) as compared with group I (40.8$\pm$4.7mmHg) and LVDP at 20 minutes of the reperfusion was significantly higher in group II(74$\pm$5.3mmHg p<0.01) and group III(72$\pm$5.6mmHg p<0.025) as compared with group I (44.2$\pm$4.6mmHg). Percentage recovery of LVDP at the reperfusion was the highest in group II(123.3%) Percentage recovery of coronary flow at the equilibrium reperfusion were higher in group II(310%, 270%) group III(230%, 290%) group IV(310%, 280%) as compared with group I (100%) respectively. Myocadial LDH level was significant lower in group IV(33495$\pm$1802 IU/gm p<0.04) as compared with group I(48767$\pm$1421 IU/gm) Myocadial CK-MB level was significant higher in group II(74820$\pm$1421 IU/gm) compared with group I (45450$\pm$1737 IU/gm) Myocadial ADA level was significant higher group IV(1215$\pm$8 IU/gm p<0.05) compared with group I(125$\pm$15 IU/gm) but there was no significant difference between group I and group II ,III, IV in changes of coronary effluent LDH, a-HBD levels. Conclusion: C-AMP PDSI solely appears to have a better effect on myocardial preservation after ischemia than NBT but with no synergistic effect and it could keep CK-MB leve high in myocardial tissues.

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Myocardial Protection of Contractile Function After Global Ischemia by Compound K in the Isolated Heart

  • Kim, Jong-Hoon
    • Journal of Ginseng Research
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    • v.33 no.4
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    • pp.268-277
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    • 2009
  • Ginsenosides are among the most well-known traditional herbal medicines frequently used for the treatment of cardiovascular symptoms in South Korea. The anti-ischemic effects of compound K (CK), a metabolite of ginsenoside Rb1, on ischemia-induced isolated rat hearts were investigated through the analyses of the changes in the hemodynamics (blood pressure, aortic flow, coronary flow, and cardiac output) and the measurement of the infarct region. The subjects in this study were divided into four groups: the normal control, the CK-alone group, the ischemia-induced group without any treatment, and the ischemia-induced group treated with CK. No significant differences in perfusion pressure, aortic flow, coronary flow, and cardiac output were found between the groups before ischemia was induced. The oxygen and buffer supply was stopped for 30 min to induce ischemia 60 min after reperfusion in the isolated rat hearts, and the CK was administered 5 min before ischemia induction. The CK treatment significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions. In addition, the hemodynamics (except for the heart rate) of the group treated with CK significantly recovered 60 min after reperfusion, unlike in the control group. CK significantly limited the infarct. These results suggest that CK treatment has distinct anti-ischemic effects in an exvivo model of an ischemia-reperfusion-induced rat heart.

Effect of Rosiglitazone on Myocardial Ischemia-Reperfusion Injury in Rat Heart

  • Ha, Ki-Chan
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.4
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    • pp.181-186
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    • 2006
  • This study was undertaken to evaluate whether peroxisome proliferator-activated-receptor-gamma $(PPAR-{\gamma})$ agonist-rosiglitazone (ROSI) induces postischemic functional recovery in Langendorf heart model. Hearts isolated from normal rats were subjected to 20 min of normoxia or 25 min zero-flow ischemia followed by 50 min reperfusion. In this acute protocol, ROSI $(20\;{\mu}g/ml)$ administered 10 min before ischemia had no effect on hemodynamic cardiac function, but had protective effect on lipid peroxidation in in vitro experiments. In chronic protocol in which ROSI was given by daily gavage (4 mg/kg) for three consecutive days, ROSI could not prevent the hemodynamic alteration on cardiac performance, but has protective effect on the activity of superoxide dismutase (SOD). There was no significant difference in the contents of reduced glutathione (GSH) and catalase activity between ischemia-reperfusion (IR) and ROSI treated IR hearts. Although ROSI had no effect on hemodynamic factor, it had effect on antioxidant activity. Our results indicate that ROSI provides partial beneficial effects by inhibiting lipid peroxidation and/or recovering normal level of SOD activity in the ischemic reperfused heart.

Cardiac Valve Replacement and Simultaneous Myocardial Revascularization (심장판막질환과 동반된 관상동맥질환의 수술)

  • Reiner, Korfer;Jee, Heng-Ok
    • Journal of Chest Surgery
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    • v.21 no.1
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    • pp.164-168
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    • 1988
  • Between November, 1984, and May, 1986, 93 patients underwent combined valvular and coronary artery operation. They were 70 male and 23 female, the age ranging from 29 to 82. From this population 89 patients underwent single valve replacement and 4 patients underwent double valve replacement. Patients with mitral valve disease were in the majority present in the age group between 50 till 70, where as in the group after 60 years, patients with aortic valve disease were dominant. The main indication for aortic valve replacement was aortic stenosis and the indication for mitral valve replacement was equal between mitral stenosis and mitral incompetence, the later was due to papillary dysfunction after myocardial infarction. Dyspnea was a very frequent symptom and it was found in nearly all patients. 28 patients had a previous myocardial infarction and severe left ventricular dysfunction. The grafts were placed prior to valve replacement and periods of myocardial ischemia were kept at a minimum by maintaining coronary perfusion throughout the operation. It is our opinion that simultaneous valve replacement and myocardial revascularization does not increase the risk of cardiac valve replacement substantially.

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A Simulation of the Cardiac Ischemia Using Three Dimensional Ventricular Model (3차원 심실모델을 이용한 심근허혈 시뮬레이션)

  • Lee, Kyoung-Joung;Yoon, Hyung-Ro
    • Proceedings of the KOSOMBE Conference
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    • v.1994 no.12
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    • pp.61-64
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    • 1994
  • This paper describes the construction of an anisotropic three dimensional ventricular model based on the bidomain model. The cardiac artivation process in the normal cardiac cell and the myocardiac ischemic cell are simulated by the Huygen's principle. The depolarization process in the myocardial ischemia displays the delayed activation compared to the normal state. The repolarization process is simulated by the myocardial potential at the arbitrary ellapsed time after activation process.

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Left Ventricular Function Changes Under Normothermic Krebs Perfusate in Newborn Piglet (신생 돼지심장에서 상온의 Krebs 용액 관류에 따른 좌심실 기능의 변화)

  • O, Bong-Seok;Na, Guk-Ju;Lee, Dong-Jun
    • Journal of Chest Surgery
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    • v.23 no.6
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    • pp.1067-1073
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    • 1990
  • To clarify the changes of left ventricular function under normothermia, the time interval between the onset of ischemia and the beginning of contracture of left ventricle[TIC] were recorded in newborn piglet. Myocardial performance was assessed using intraventricular balloon to determine compliance and systolic function after 5 to 10 minutes interval per-fusing normothermic substrate free Krebs solution as a perfusate. The time to onset TIC was 29.5\ulcorner1.7 minutes and peak ischemic contracture was 46.7\ulcorner4.0 minutes[p<0.01]. In myocardial performance, systolic function of left ventricle[defined as cardiac contractility] was kept until 25 minutes of perfusion, but was decreased abruptly after 30 minutes of perfusion[p<0.0018] and diastolic function of left ventricle[defined as diastolic compliance] was kept until 15 minutes of perfusion, but was decreased after 20 minutes of perfusion [p=0.00\ulcorner9]. This study demonstrated maximal time of the tolerance to normothermic global ischemia and functional changes of left ventricle using Krebs perfusate under the same condition.

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