• Journal of Chest Surgery
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• v.31 no.6
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• pp.567-575
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• 1998

Panax Ginseng C.A. Meyer has been known for hundreds of years as the most valuable drug having mysterious effects among all the herbal medicines and plants in Korea. Also, many experimental studies have been performed recently that the various effects were identified and applied clinically. So we attempted an experimental study on the effect of ginsenoside Rg1 mixtures in an isolated rat heart with the use of the Langendorff model. The objective of this study was to determine whether this ginsenoside Rg1 mixtures would protect the myocardial injury after ischemic arrest and reperfusion. Isolated rat hearts were allowed to equilibrate for 20 minutes and were then subjected to 15 minutes of normothermic ischemia. After this ischemic period, isolated rat hearts were allowed to reperfusion for 10 minutes(Ischemic Group). In other group , isolated rat hearts were perfused for 60 minutes continuously with normothermia( Normothermic Group). Hemodynamic and biochemical parameters such as heart rate, left ventricular pressure, +dp/dt max, coronary blood flow and cardiac enzymes were measured during initial perfusion, ischemia, reperfusion period (Ischemic group) and 20, 40 and 60 minutes after continuous perfusion(Normothermic group). After completion of the experiment, this data was evaluated and the following results were obtained. 1. Heart rates showed an increase in both ischemic and normothermic experimental groups, but statistically significant differences were not identified. 2. LVP(Left Ventricular Pressure) showed statistically significant differences in both ischemic and normothermic experimental groups(p<0.005, p<0.01). 3. +dp/dt max showed statistically significant differences in both ischemic and normothermic experimental groups(p<0.01, p<0.01). 4. There were no statistically significant differences in coronary blood flow and cardiac cenzymes in all groups, but experimental groups seemed to have better protection and recovery. These results suggest that ginsenoside Rg1 mixtures has a protective effect on the myocardial injury after ischemia and reperfusion.

• Clinical and Experimental Pediatrics
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• v.45 no.5
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• pp.560-567
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• 2002

주산기 뇌손상은 주로 급격한 저산소-허혈 손상에 의하는데 급격한 산소 공급의 차단은 oxidative phosphorylation을 정지 시켜서 뇌대사를 위한 에너지 공급이 차단되게 된다. 에너지 공급이 차단된 뇌세포는 뇌세포막에서 세포 내외의 이온 농도 차를 유지시키던 ATP-dependent $Na^{+}-K^{+}$ pump의 기능이 정지 되고, 세포 내외의 농도 차에 따라 $Na^{+}$, $Cl^{+}$, $Ca^{{+}{+}}$의 대규모 세포 내로 이동이 일어난다. 세포 내로 calcium 이온의 이동은 glutamate 수용체의 활성화에 의해서도 일나는데, 세포 내 calcium 이온의 증가는 protease, lipase, nuclease 등을 활성화 시켜 세포를 사망에 이르게 하는 연속적이고 다양한 생화학적 반응을 일으키게 된다. Glutamate는 대표적인 신경 전달 물질인데 저산소-허혈 손상 시 glutamate 수용체의 지나친 흥분은 미성숙 뇌에 뇌손상을 유발하는데, NMDA 또는 non-NMDA 수용체와 복합체를 형성하고 있는 calcium 이동 통로를 활성화 시켜 세포 내 calcium 이온을 증가시키고, 그 외에 metabotropic recetor는 G-protein의 활성화 등을 통해 뇌손상을 유발하는 다양한 생화학적 반응을 매개한다. 저산소-허혈 손상 후 재산소화와 재관류가 일어나면서 뇌세포의 지연성 사망(secondary neuronal death)이 일어나는데 이는 초기 손상 후 뒤이어 일어나는 다양한 생화학적 반응에 의하는데 다량의 산소 자유기 발생, nitric oxide의 생성, 염증 반응과 싸이토카인, 신경전도 물질의 과흥분 등이 관여하며, 신경 세포 사망은 세포괴사(necrosis)뿐 아니라 일부는 세포 사멸(apoptosis)로 알려진 의도된 세포 사망(programmed cell death)에 의한 것으로 생각되고 있다(Fig. 2).

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.109-118
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• 1991

The present study was conducted to assess the possible contribution of arachidonic acid to generation of reactive oxygen metabolites and myocardial damage in ischemic-reperfused heart. Langendorff preparations of isolated rat heart were made ischemic by hypoperfusion (0.5 ml/min) for 45 min, and then followed by normal oxygenated reperfusion (7 ml/min). The generation of superoxide anion was estimated by measuring the SOD-inhibitable ferricytochrome C reduction. The myocardial cellular damage was observed by measuring LDH released into the coronary effluent. Oxygenated reperfusion following a period of ischemia produced superoxide anion, which was inhibited by both indomethacin (60 nmole/ml) and ibuprofen $(30\;{\mu}g/ml)$. Sodium arachidonate $(10^{-7}-10^{-2}{\mu}g/ml)$ administered during the period of oxygenated reperfusion stimulated superoxide anion production dose-dependently. The rate of arachidonate-induced superoxide generation was markedly inhibited by indomethacin, a cyclooxygenase inhibitor; nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, and by eicosatetraynoic acid (ETYA), a substrate inhibitor of arachidonic acid metabolism. The release of LDH was increased by Na arachidonate and was inhibited by superoxide dismutase. The release of LDH induced by arachidonic acid was also inhibited by indomethacin, NDGA and ETYA. In conclusion, the present result suggests that arachidonic acid metabolism is involved in the production of reactive oxygen metabolite and plays a contributory role in the genesis of reperfusion injuy of myocardium.

• Journal of Chest Surgery
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• v.33 no.7
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• pp.531-540
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• 2000

Baclgrpimd; Recent studies have suggested that the cardioprotective effect of ischemic preconditioning(IP) is closely related to glycogen depletion and attenuation of intracellular acidosis. In the present study, the authors tested this hypothesis by perfusion isolated rabbit hearts with glucose(G) is closely related to glycogen depletion and attenuation of intracellular acidosis. In the present study, the authors tested this hypothesis by perfusion isolated rabbit hearts with glucose(G)-free perfusate. Material and Method; Hearts isolated from New Zealand white rabbits(1.5~2.0 kg body weight) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to 45 min global ischemia followed by 120 min reperfusion with IP(IP group, n=13) or without IP(ischemic control group, n=10). IP was induced by single episode of 5 min global ischemia and 10 min reperfusion. In the G-free preconditioned group(n=12), G depletion was induced by perfusionwith G-free Tyrode solution for 5 min and then perfused with G-containing Tyrode solution for 10 min; and 45 min ischemia and 120 min reperfusion. Left ventricular functionincluding developed pressure(LVDP), dP/dt, heart rate, left ventricular end-distolic pressure(LVEDP) and coronary flow (CF) were measured. Myocardial cytosolic and membrane PKC activities were measured by 32P-${\gamma}$-ATP incorporation into PKC-specific peptide and PKC isozymes were analyzed by Western blot with monoclonal antibodies. Infarct size was determined by staining with TTC(tetrazolium salt) and planimetry. Data were analyzed by one-way analysis of variance (ANOVA) and Turkey's post-hoc test. Result ; In comparison with the ischemic control group, IP significantly enhanced functional recovery of the left ventricle; in contrast, functional significantly enhanced functional recovery of the left ventricle; in contrast, functional recovery were not significantly different between the G-free preconditioned and the ischemic control groups. However, the infarct size was significantly reduced by IP or G-free preconditioning(39$\pm$2.7% in the ischemic control, 19$\pm$1.2% in the IP, and 15$\pm$3.9% in the G-free preconditioned, p<0.05). Membrane PKC activities were increased significantly after IP (119%), IP and 45 min ischemia(145%), G-free [recpmdotopmomg (150%), and G-free preconditioning and 45 min ischemia(127%); expression of membrane PKC isozymes, $\alpha$ and $\varepsilon$, tended to be increased after IP or G-free preconditioning. Conclusion; These results suggest that in isolated Langendorff-perfused rabbit heart model, G-free preconditioning (induced by single episode of 5 min G depletion and 10 min repletion) colud not improve post-ischemic contractile dysfunction(after 45-minute global ischemia); however, it has an infarct size-limiting effect.

• Journal of Chest Surgery
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• v.29 no.6
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• pp.593-598
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• 1996

The large number of past investigation on extended myocardial protection clearly indicates that cold potassium cardioplegia and topical cooling have limited capabilities. Accordingly, more recent experimen- tal approaches have focused on the modalities of reperfusion and their implication on postischemic myo- cardial recovery. Oxygen may play a crucial role in the development of ischemic and reperfusion injury. Reactive oxygen radicals may be produced during ischemia or reperfusion after incomplete reduction of molecular oxygen or from other pathway and then induce fatal injury of the heart. The important obser- vation of oxygen-induced myocardial damage during reperfusion has led to the concept of applying oxy- gen free radical scavengers. So, this study is on dietary vitamin C supplementation as antioxidant in rats to determine whether or not they have a higher tolerance against cardiac ischemia-reperf'usion injury under Langendorff system. Male or female Sprague-Dawley rats (190-33Og) were randomly separated into two groups. Group A was not treated(n=10). Group B received vitamin C supplement (n=10). Experiment was performed 24 hours after vitamin C 200mg fed orally as injectable ascorbic acid. There were significant differences in contractile parameters between control and vitamin C-treated group. The RLVP (r te of post/preischemic left ventricular pressure) and Rdp/dt (rate of post/preischemic dp/dt) were significant statistically between two groups (p<0.05). But, RHR (rate of post/preischemic heart rate), time to first beat and sta'utilization were not significant. In conclusion, pretreatment with the antioxidant, ascorbic acid, was found to preserve left ventricular contractile function. But the precise mechanism of action of ascorbic acid has not as yet been determined, so further study will be required.

• The Journal of Korean Physical Therapy
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• v.15 no.4
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• pp.199-207
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• 2003

This review describes the neurophathological mechanisms that are implicated in perinatal brain injury. Perinatal brain injury is the most important cause of morbidity and mortality to infants, often leading to spastic motor deficits, mental retardation, seizures, and learning impairments. The immature brain injury is usually caused by cerebral hypoxia-ischemia, hemorrhage, or infection. The important form of perinatal brain injury is the hypoxic-ischemic injury and the cerebral hemorrhage. The pathology of hypoxic-ischemic injury include delayed energy failure by mitochondrial dysfunction, neuronal excitotoxicity and vulnerability of white matter in developing brain. The immature brain has the fragile vascular bed of germinal matrix and can not effectively centralize their circulation. Therefore, the cerebral hemorrhage process is considered to be involved in the periventricular leukomalacia.

• Journal of Life Science
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• v.19 no.6
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• pp.818-824
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• 2009

The mechanisms responsible for ischemia/reperfusion (I/R) injury have direct or indirect relevance to clinical lung injury after severe shock, cardiopulmonary bypass, and transplantation. This study investigated the effects of aspirin on intestinal I/R-induced acute lung injury (ALI) in rats. Lipopolysaccharide (LPS) induced cyclooxygenase-2 (COX-2) expression in A549 and RAW264.7 cells. RAW264.7 macrophages had shown greater expression of COX-2 than A549 cells. In addition, the NADPH oxidase inhibitor apocynin and p38 MAPK inhibitor SB203580 attenuated LPS-stimulated COX-2 expression. To induce ALI, intestinal ischemia was performed for 60 min prior to the 4 hr reperfusion by clamping the superior mesenteric artery in Sprague-Dawley rats. In order to test and compare the effect of non-specific COX inhibitor aspirin with the effect of mepacrine, a well known phospholipase$A_{2}$ inhibitor, rats were divided into 4 groups: Sham, I/R, Mepa+I/R (mepacrine, 60 mg/kg, i.p.), ASA+I/R (aspirin, 10 mg/kg, i.p.). In the present investigation, myeloperoxidase activities in the lung and intestinal tissues were increased by I/R. These changes were reduced by single pretreatment of mepacrine (60 mg/kg, i.p.) or aspirin (10 mg/kg, i.p.) 30 min before I/R. Structural studies demonstrated that the tissue injuries in the lung and intestine after I/R were also attenuated by the pretreatment of mepacrine or aspirin. These results suggest that I/R-induced ALI is mediated, in part, by the activation of COX. In addition, pretreatment of aspirin might be helpful for the prevention of ALI in ARDS-prone patients. In addition, the p38 MAPK inhibitor and apocynin also might be helpful to ALI through the inhibition of COX-2 expression.

• Journal of Chest Surgery
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• v.32 no.5
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• pp.413-421
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• 1999

Background: Ischemia reperfusion injury is known to contribute to the major causes of the early graft failure in lung transplantation. Triiodothyronine (T3) has been suggested to ameliorate ischemia reperfusion injury from both in vivo and in vitro experiments of various organs. Prospecting its beneficial effect for pulmonary allograft preservation, we made a new solution by adding T3 into the extracellular type dextran solution. Material and Method: Twelve adult mongrel dogs underwent left lung allotransplantation. Six donor dogs were flushed with the new solution(Group 1, n=6), and the remaining six were flushed with Euro-Collins solution to serve as controls(Group 2, n=6). Allografts were stored in each preservation solution for 20 hours at 4$^{\circ}C$. Left single lung transplantations were performed. The right pulmonary artery and the right main bronchus were clamped at 15 minutes after the reperfusion and maintained throughout the experiment to evaluate the transplanted left lung function. Result: Arterial carbon dioxide tension was better in group 1 than in group 2 throughout the experiment period and the difference was statistically significant at 2 hours after reperfusion(28.0${\pm}$3.0 mmHg and 53.1${\pm}$17.4 mmHg, p<0.05). The differences of arterial oxygen partial pressure, peak airway pressure and pulmonary vascular resistance showed no statistical significance. The malondialdehyde(MDA) level, measured from tissue obtained at 120 minutes after reperfusion showed no statistically significant difference. The tissue wet/dry ratio of group 1(649${\pm}$27 %) was significantly lower than that of group 2(686${\pm}$71 %, p<0.05). The microscopic examination revealed varying degrees of injury represented mainly by findings such as perivascular neutrophil infiltration, capillary hemorrhage and interstitial congestion. These findings were less severe in group 1 than those in group 2. Conclusion: The new solution demonstrated superior allograft preservation after 20 hour ischemia compared to Euro-Collins solution in canine single left lung transplantation model, these results suggest that T3 might be a promising agent for pulmonary allograft preservation.

• Journal of Life Science
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• v.32 no.7
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• pp.567-577
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• 2022

Recently, the prevalence of ischemic diseases, such as ischemic heart disease, cerebral ischemia, and peripheral arterial disease, has been continuously increasing due to the aging population. The current standardized treatment for ischemic diseases is reperfusion therapy through pharmacotherapy and surgical approaches. Although reperfusion therapy may restore the function of damaged arteries, it is not effective at restoring the function of the surrounding tissues that have been damaged due to ischemia. Therefore, it is necessary to develop a new treatment strategy that can safely and effectively treat ischemic damage and restore the function of surrounding tissues. To overcome these limitations, stem cell-based therapy to regenerate the damaged region has been studied as a promising strategy for ischemic vascular diseases. Mesenchymal stem cells (MSCs) can be isolated from diverse tissues and have been shown to be promising for the treatment of ischemic disease by regenerating damaged tissues through immunomodulation, the promotion of angiogenesis, and the secretion of various relevant factors. Moreover, new approaches to enhancing MSC function, such as cell priming or enhancing transplantation efficiency using a 3D culture method, have been studied to increase stem cell therapeutic efficacy. In this review, we provide various strategies by which MSCs are used to treat ischemic diseases, and we discuss the challenges of MSC transplantation, such as the differentiation, proliferation, and engraftment of MSCs at the ischemic site.

• Journal of Chest Surgery
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• v.34 no.11
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• pp.823-830
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• 2001

Background: Paraplegia is a serious complication of thoracic or thoracoabdominal aortic operations, which is related to ischemic injury of the spinal cord induced by low perfusion pressure during cross clamping of the aorta. Ischemic preconditioning of heart or brain with reversible sublethal ischemic injury induces resistance to subsequent lethal ischemia. The aim of this study is to investigate whether ischemic tolerance could be induced by the preconditioning of the spinal cord using swine model. Material and Method: The animals were randomly assigned to three groups: sham group(n=3), control group(n=6) and pre-conditioning group(n=8). In the sham group, we performed the left thoracotomy only without any ischemic injury. In the preconditioning group, the swine received reversible spinal cord ischemic injury by aortic clamping for 20 minutes, whereas control group had no previous aortic cross- clamping. Forty-eight hours later, the aorta was clamped for 30 minutes in both groups. Neurological examination was done 24 hours later, then the animals were euthanized for histopathology and malonedialdehyde(MDA) spectrophotometry assay of the spinal cord. Result: Statistically significant difference in neurological outcome was observed between the control and preconditioning groups at 24 hours after ischemic injury. The incidence of paraplegia and severe paresis was 100% in the control group, and 62.5% in the preconditing group(p=0.028). There was no statistically significant difference in histopathology and MDA assay of the ischemic spinal cord between these two groups with borderline statistical difference in MDA assay(p=0.0745). Conclusion: In the present swine study, ischemic preconditioning could induce tolerance against 30 minute ischemic insult of the spinal cord, although the animals did not completely recover(stand-up or walk). We expect that combining this preconditioning with other currently existing protection methods might lead to a synergistic effect, which warrants further investigation.