• The Korean Journal of Physiology and Pharmacology
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• v.22 no.6
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• pp.661-670
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• 2018

Fimasartan, a new angiotensin II receptor antagonist, reduces myocyte damage and stabilizes atherosclerotic plaque through its anti-inflammatory effect in animal studies. We investigated the protective effects of pretreatment with fimasartan on ischemia-reperfusion injury (IRI) in a mouse model of ischemic renal damage. C57BL/6 mice were pretreated with or without 5 (IR-F5) or 10 (IR-F10) mg/kg/day fimasartan for 3 days. Renal ischemia was induced by clamping bilateral renal vascular pedicles for 30 min. Histology, pro-inflammatory cytokines, and apoptosis assays were evaluated 24 h after IRI. Compared to the untreated group, blood urea nitrogen and serum creatinine levels were significantly lower in the IR-F10 group. IR-F10 kidneys showed less tubular necrosis and interstitial fibrosis than untreated kidneys. The expression of F4/80, a macrophage infiltration marker, and tumor necrosis factor $(TNF)-{\alpha}$, decreased in the IR-F10 group. High-dose fimasartan treatment attenuated the upregulation of $TNF-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 in ischemic kidneys. Fewer TUNEL positive cells were observed in IR-F10 compared to control mice. Fimasartan caused a significant decrease in caspase-3 activity and the level of Bax, and increased the Bcl-2 level. Fimasartan preserved renal function and tubular architecture from IRI in a mouse ischemic renal injury model. Fimasartan also attenuated upregulation of inflammatory cytokines and decreased apoptosis of renal tubular cells. Our results suggest that fimasartan inhibited the process of tubular injury by preventing apoptosis induced by the inflammatory pathway.

• Journal of Veterinary Clinics
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• v.24 no.2
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• pp.94-98
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• 2007

This study was to investigate the effects of ascorbic acid and alpha-tocopherol on the attenuation of renal ischemia-reperfusion (IR) injury in pigs. Ten pigs were subjected to 60 minutes of warm unilateral renal ischemia followed by removal of contralateral kidney and then divided into two groups. Treatment group was performed ascorbic acid and alpha-tocopherol pretreatment 2 days before operation and ascorbic acid with heparin-saline solution irrigation-aspiration. Otherwise, control group used only irrigation-aspiration of heparin-saline solution. Blood samples were collected from these pigs for measurement of serum blood urea nitrogen (BUN) and creatinine values, antioxidant superoxide dismutase (SOD) at pre, day 1, day 3, day 7 and day 14. The kidneys were taken for histopathologic evaluation after euthanasia on postoperative day 14. The levels of BUN were significantly increased in the control group on day 1, day 3 and day 7 (P<0.05). And the level of creatinine was significantly increased in the control group on day 3 (p<0.05). Activity of antioxidant enzymes in plasma revealed significant difference (p<0.05) between control and treatment group at day 14. In histopathologic findings, treatment group was showed less damage than that of control group on the basis of renal tubular damage. It was concluded that ascorbic acid and alpha-tocopherol attenuated renal I/R injury in the pigs.

• Journal of Ginseng Research
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• v.31 no.1
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• pp.23-33
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• 2007

Ginsenosides are one of the most well-known traditional herbal medicines frequently used for the treatment of cardiovascular symptoms in korea. The anti-ischemic effects of the mixture of ginsenoside $Rg_3$, and CK on ischemia-induced isolated rat heart were investigated through analyses of changes in hemodynamics ; blood pressure, aortic flow, coronary flow, and cardiac output. The subjects in this study were divided into four groups: normal control, the mixture of ginsenoside $Rg_3$ and CK, an ischemia-induced group without any treatment, and an ischemia-induced group treated with the mixture of ginsenoside $Rg_3$ and CK. There were no significant differences in perfusion pressure, aortic flow, coronary flow and cardiac output between them before ischemia was induced. The supply of oxygen and buffer was stopped for five minutes to induce ischemia in isolated rat hearts, and the mixture of ginsenoside $Rg_3$ and CK was administered during ischemia induction. Treatments of the mixture of ginsenoside $Rg_3$ and CK significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions. In addition, hemodynamics (except heart rate) of the group treated with the mixture of ginsenoside $Rg_3$ and CK significantly recovered 60 minutes after reperfusion compared to the control group (mixture+ischemia vs ischemia - average perfusion pressure: 74.4${\pm}$2.97% vs. 85.1${\pm}$3.01%, average aortic flow volume: 49.11${\pm}$2.72% vs. 59.97${\pm}$2.93%, average coronary flow volume: 58.50${\pm}$2.81% vs. 72.72${\pm}$2.99%, and average cardiac output: 52.47${\pm}$2.78% vs. 63.11${\pm}$2.76%, p<0.01, respectively). These results suggest that treatment of the mixture of ginsenoside $Rg_3$ and CK has distinct anti-ischemic effects in ex vivo model of ischemia-induced rat heart.

• Journal of Chest Surgery
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• v.37 no.2
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• pp.119-130
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• 2004

Decrease in cardiac function after open heart surgery is due to an ischemia induced myocardial damage during surgery, and ischemic preconditioning, a condition in which the myocardial damage does not accumulate after repeated episodes of ischemia but protects itself from damage after prolonged ischemia due to myocytes tolerating the ischemia, is known to diminish myocardial damage, which also helps the recovery of myocardium after reperfusion, and decreases incidences of arrythmia. Our study is performed to display the ischemic preconditioning and show the myocardial protective effect by applying cardioplegic solution to the heart removed from rat. Material and Method: Sprague-Dawley male rats were used, They were fixed on a modified isolated working heart model after cannulation. The reperfusion process was according to non-working and working heart methods and the working method was executed for 20 minutes in which the heart rate, aortic pressure, aortic flow and coronary flow were measured and recorded. The control group is the group which the extracted heart was fixed on the isolated working heart model, recovered by reperfusion 60 minutes after infusion and preserved in the cardioplegic solution 20 minutes after the working heart perfusion and aortic cross clamp, The thesis groups were divided into group I, which ischemic hearts that were hypoxia induced were perfused by cardioplegic solution and preserved for 60 minutes; group II, the cardioplegic solution was infused 45 seconds (II-1), 1 minutes (II-2), 3 minutes (II-3), after the ischemia induction, 20 minutes after working heart perfusion and aortic cross clamp; and group III, hearts were executed on working heart perfusion for 20 minutes and aortic cross clamp was performed for 45 seconds (III-1), 1minute (III-2), 3 minutes (III-3), reperfused for 2 minutes to recover the heart, and then aortic cross clamping was repeated for reperfusion, all the groups were compared based on hemodynamic performance after reperfusion of the heart after preservation for 60 minutes. Result: The recovery time until spontaneous heart beat was longer in groups I, II-3, III-2 and III-3 to control group (p<0.01). Group III-1 (p<0.05) had better results in terms of recovery in number of heart rates compared to control group, and recovered better compared to II-1 (p<0.05). The recovery of aortic blood pressure favored group III-1 (p<0.05) and had better outcomes compared with II-1 (p<0.01). Group III-1 also showed best results in terms of cardiac output (p<0.05) and group III-2 was better compared to II-2 (p<0.05). Group I (p<0.01) and II-3 (p<0.05) showed more cardiac edema than control group. Conclusion: When the effects of other organs are dismissed, protecting the heart by infusion of cardioplegic solution after enforcing ischemia for a short period of time before the onset of abnormal heart beats for preconditioning has a better recovery effect in the cardioplegic group with preconditioning compared to the cardioplegic solution itself. we believe that further study is needed to find a more effective method of preconditioning.

• Journal of Chest Surgery
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• v.32 no.11
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• pp.978-983
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• 1999

Background: Complement activation with transpulmonary leukocyte sequestration is considered a main mediator leading to ischemia-reperfusion lung(I-R) injury. We studied the role of leukocytes in the formation of I-R injury in ovine cardiopulmonary bypass(CPB) model with a membrane oxygenator. Material and Method: Five sheep were used. CPB circuitry consisted of a roller pump(American Optical Corp., Greenwich, CT, USA) and a membrane oxygenator(UNIVOX-IC, Bentley, Baxter Health Corp, Irvine, CA, USA). The CPB time was fixed at 120 min. Ten minutes after the start of CPB, total CPB was established. Thereafter a total CPB of 100 min was performed, followed by another 10 min of partial CPB. The CPB was discontinued and the animals were fully recovered. For measuring left and right atrial leukocyte counts, blood samples were taken before thoracotomy, 5 min and 109 in after the start of CPB, and 30 min and 120 min after weaning. C3a was measured before thoracotomy, 109 min after the start of CPB, and 30 min and 120 min after weaning. Plasma malondialdehyde(MDA) was checked before thoracotomy, 109 min after the start of CPB, and 30 min after weaning. One to two grams of lung tissue were taken for water content measurement before thoracotomy, 109 min after the start of CPB, and 30 min after weaning. Lung biopsy specimens were examined by light and electron microscopy. Result: Of 5 animals, 4 survived the experimental procedures. Of these, 3 animals survived on a long-term basis. No significant differences in transpulmonary gradients of leukocyte were found and no significant complement activation was expressed by C3a levels. MDA level did not show significant changes related to lung reperfusion despite an increase after the start of CPB. On both light and electron microscopic examinations, mild to moderate acute lung change was observed. Interstitial edema, leakage of erythrocytes into the alveolar space and endothelial cell swelling were the main findings. Water content of the lung showed a slight increase after the start of CPB, but there was no statistical significance. Conclusion: These findings indicate that ischemia-repersusion lung injury may not be from complement activation-leukocyte sequestration but from another source of oxygen free radicals related to CPB.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.5
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• pp.1194-1201
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• 2003

Jaeumgenby-tang(JGT) have been used in oriental medicine for many centries as a therapeutic agent of vertigo caused by deficiency of qi(氣) and blood(血). Effect of Aurantii Fructus(AF) take off the phlegm by promoting the circulation of qi, Gastrodae Rhizoma(GR) has effects treating for headarch, vertigo by calming the liver and suppressing hyperactivity of the liver-yang (陽). I investigated whether injection of JGT adding AFㆍGR extract(JTG) affects cerebral hemodynamics [regional cerebral blood f1ow(rCBF), pial arterial diameter(PAD) in cerebral ischemia rats by MCA occlusion method, and I designed to make manifest whether JTG is mediated by adrenergic β-receptor, cyclooxygenase or guanylate cyclase. The changes of rCBF was determinated by laser-doppler flowmetry(LDF), and the changes of PAD was determinated by video microscope and width analyzer. The results were as follows in cerebral ischemic rats; The changes of rCBF and PAD were increased stabilizly by treatment with JTG(10 ㎎/kg, i.v.) during the period of cerebral reperfusion, and pretreatment with propranolol and indomethacin were increased JTG induced increase of rCBF and PAD during the period of cerebral reperfusion. Pretreatment methylene blue was decreased JTG induced increase of rCBF and PAD during the period of cerebral reperfusion. In conclusion, JTG causes a diverse response of rCBF and PAD, and action of JTG is mediated by adrenergic β-receptor and cyclooxygenase. I suggest that JTG has an anti-ischemic effect through the improvement of crebral hemodynamics.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.76-76
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• 2020

Stachys sieboldii Miq. (chinese artichoke), which has been extensively used in oriental traditional medicine to treat of ischemic stroke; however, the role of Stachys sieboldii Miq. (SSM) in cerebral ischemia/reperfusion (I/R) injury is not yet fully understood. In the current study, the neuroblastoma cell line (SH-SY5Y) were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate I/R injury in vitro model. The results showed that SSM improved OGD/R-induced inhibitory effect on cell viability of SH-SY5Y Cells. SSM displayed anti-oxidative activity as proved by the decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in OGD/R-induced SH-SY5Y Cells. In addition, cell apoptosis was markedly decreased after SSM treatment in OGD/R-induced SH-SY5Y Cells. The up-regulation of Bcl-2 and down-regulation of Bax, thus reducing the Bax/Bcl-2 ratio that in turn protected the activation of caspase-9 and -3, and inhibition of poly (ADP-ribose) polymerase cleavage, which was associated with the blocking of cytochrome c release to the cytoplasm. Collectively, SSM protected human neuroblastoma SH-SY5Y cells from OGD/R-induced injury via preventing mitochondrial-dependent pathway through scavenging excessive ROS, suggesting that SSM might be a potential agent for the ischemic stroke therapy.

• The Journal of Korean Medicine
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• v.18 no.2
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• pp.340-354
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• 1997

Background : The stenosis of the coronary artery results in a decrease in the myocardial oxygen supply, ischemia and infarction. Jakamchotang as a drug of liquid is generally regarded to have the effect of arrythmia, palpitation from Heart disease and promoting the flow of Ki and Blood. Methods : The purpose of this experimental study is to find whether Jakamchotang is effective or not in curing ischemia in isolated perfused rat hearts and to measure the degree of its curing effect. In this study, under the Langendorff apparatus, ischemia was induced in isolated Sprague-Dawley rat hearts by ceasing the perfusion for 20 minites. Subjects were divided into a normal saline orally administered group(control group), an Jakamchotang orally 100mg administered group (sample A), an Jakamchotang orally 300mg administered group (sample B), and an Jakamchotang injection perfused group(sample C). The heart rates, left ventricular pressure, myocardial dilatation/contraction, cardiac perfusion flow and cardiac ezyme(LDH, CPK) of the four group were measured and compared in order to assess the influence of Jakamchotang on isolated perfused rat hearts recovering abillity from ischemia and infarction. results : 1. Heart rates were increased significantly in Jakamchotang orally 100mg administered group, Jakamchotang orally 300mg administered group and Jakamchotang injection perfused group on perfusion and reperfusion(p<0.01). 2. Left ventricular pressure were increased significantly in Jakamchotang orally 100mg administered group and 300mg administered and Jakamchotang injection perfused group(p<0.01) in comparison with control group on perfusion, but every group did not significant on reperfusion. 3. While there were no differances in each group's abillities of myocardial dilatation, the ability of myocardial constriction of Jakamchotang 100mg administered group only on perfusion was significantly greater than that of control group(p<0.05). 4. CBF was no significant on perfusion and reperfusion in comparison with control group(N.S.) 5. LDH was not significantly decreased on perfusion, but significactly decreased in Jakamchotang orally 100mg administered group, Jakamchotang orally 300mg administered group on reperfusion. 6. CPK was significantly decreased in Jakamchotang orally 100mg administered group, 300mg administered and Jakamchotang injection perfused group on perfusion(p<0.01), but was not significantly in Jakamchotang 300mg administered group only on reperfusion(P<0.05) Conclusion : According to the result above, Jakamchotang have an effect to recover in the isolated perfused rat hearts. Especially, the effect of Jakamchotang in orally adminstered group is greater than that of Jakamchotang injection perfused group on preischemia. The followings are the two important results of this study: First, the effect of Jakamchotang used traditionally on heart disease was proved statistcally under the Langendorff apparatus. Second, on the basis of this study, the effect of other type medications on myocardial ischemia can be evaluted in further studies.

• Journal of Chest Surgery
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• v.36 no.12
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• pp.894-903
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• 2003

Protection against ischemia-reperfusion injury is crucial for successful transplantation of the lung. It has been known that nitric oxide has many favorable effects on the donor lungs but at the same time, has some potential side effects of cytotoxicity. In this regards, we investigated whether the administration of nitroglycerin could decrease ischemia-reperfusion injury in isolated rat lung reperfusion model for the confirmation of the effect of nitroglycerin, a donor of nitric oxide, on lung transplantation. Material and Method: 35 Sprague-Dawley species male white rats were used for this experiment. For nitroglycerin group (n=18), nitroglycerin was administered intravenously followed by mixed in flushing solution for preservation. As a control group (n=17), we used the same amount of normal saline. To evaluate the effect of nitroglycerin on the lung, heart-lung block was obtained, weighed and stored in University of Wisconsin Solution at 1$0^{\circ}C$ for 24 hours. In each group of the isolated lungs, reperfusion was carried out with Krebs-Hensleit-diluted human blood for 60 minutes. As parameters of the state of the isolated lung, peak inspiratory and pulmonary arterial pressures were continuously recorded. Oxygen and carbon dioxide tension of reperfusing blood were measured before and after 30, 60 minutes of reperfusion. After sixty minutes of reperfusion, protein content in bronchoalveolar lavage fluid was measured also for the evaluation of the degree of alveolar flooding. Lung myeloperoxidase activity was determined to verify the accumulation of neutrophils. Results: Although statistically significant differences were not noted in peak inspiratory and pulmonary arterial pressure between control and nitroglycerin group, latter group showed lowering tendency of pulmonary arterial pressure during the entire reperfusion period. Oxygen tension was higher (p<0.05) in nitroglycerin group compared with that of the control group, in contrast, there were no differences in carbon dioxide tension, protein content in bronchoalveolar lavage fluid and myeloperoxidase activity between the groups. In the examination of ultrastructural changes, nitroglycerin denoted the protective effect on the pulmonary architecture compared with that of control group. Conclusion: Collectively, on the bases of these experimental results, prior treatment of donor lung with nitroglycerin could result in better preservation of the lung. Consequently, these nitroglycerin preserved lungs are thought to be more suitable for successful transplantation of the lung.

• Journal of Veterinary Clinics
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• v.26 no.2
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• pp.138-143
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• 2009

Ischemia/reperfusion injury(I/RI) is the major cause of acute renal failure and delayed graft function(DGF) unavoidable in renal transplantation. Enormous studies on ischemia damage playing a role in activating graft rejection factors, such as T cells or macrophages, are being reported. Present study was performed to determine whether ischemia time would play an important role in activating rejection-related factors or not in rat models of I/RI. Male Sprague-Dawley rats were submitted to 30, 45, and 60 minutes of warm renal ischemia with nephrectomy or control animals underwent sham operation(unilateral nephrectomy). Renal function and survival rates were evaluated on day 0, 1, 2, 3, 5 and 7. Immunofluorescence staining of dendritic cells(DCs), natural killer(NK) cells, macrophages, B cells, CD4+ and CD8+ T cells were measured on day 1 and 7 after renal I/RI. Survival rates dropped below 50% after day 3 in 45 minutes ischemia. Histologic analysis of ischemic kidneys revealed a significant loss of tubular architecture and infiltration of inflammatory cells. DCs, NK cells, macrophages, CD4+ and CD8+ T cells were infiltrated from a day after I/RI depending on ischemia time. Antigen presenting cells(DCs, NK cells or macrophages) and even T cells were infiltrated 24 hours post-I/RI, which is at the time of acute tubular necrosis. During the regeneration phase, not only these cells increased but B cells also appeared in more than 45 minutes ischemia. The numbers of the innate and the adaptive immune cells increased depending on ischemia as well as reperfusion time. These changes of infiltrating cells resulting from each I/RI model show that ischemic time plays a role in activating rejection related immune factors and have consequences on progression of renal disease in transplanted and native kidneys.