• Biomolecules & Therapeutics
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• v.13 no.3
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• pp.127-132
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• 2005

We investigated whether ischemic preconditioning (IPC) protects liver against cold ischemic injury using isolated perfused rat liver. Rat livers were preconditioned by 5 minutes of ischemia and 5 minutes of reperfusion and preserved for 30 hours at $4^{\circ}C$ in University of Wisconsin solution. Livers were then reperfused for 120 minutes. Oxygen uptake and bile flow in ischemic livers markedly decreased during reperfusion. These decreases were prevented by IPC. Portal pressure was elevated in cold ischemic and reperfused livers and this elevation was prevented by IPC. Lactate dehydrogenase and purine nucleoside phosphorylase activities markedly increased during reperfusion. These increases were prevented by IPC. The ratio of reduced glutathione to glutathione disulfide was lower in ischemic livers. This decrease was prevented by IPe. Our findings suggest that IPC protects the liver against the deleterious effect of cold ischemia/reperfusion, and this protection is associated with the reduced oxidative stress.

• The Journal of Korean Physical Therapy
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• v.13 no.1
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• pp.41-48
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• 2001

The purpose of this study was to investigate the effect of cold application on ischemia-reperfusion injury to quadriceps fomoris muscle of the hindlimbs of the rats. Nine weeks old male Sprague-Dawley white rats were divided into three groups : 1) control(only ischemia-reperfusion), 2) cold application before reperfusion(PreCold), 3) cold application after reperfusion(PostCold). All groups were 30 minute, 1 hour, 3 hours reperfusion after 2 hours ischemia with clamping abdominal artery, and investigate superoxide dismutase(SOD) immunohistochemical reaction for quadriceps femoris muscle of right hindlimb. SOD immunohistochemical reaction of experimental groups were more than the control group. Especially, SOD immunohistochemical reaction of PreCold were less than the PostCold.

• The Journal of Korean Physical Therapy
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• v.15 no.1
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• pp.171-184
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• 2003

The purpose of this study was to investigate the effect of heat application on ischemia-reperfusion injury to quadriceps femoris muscle of the rats. Nine weeks old male Sprague-Dawley white rats were divided into five groups: 1) control(only reperfusion following ischemia), 2) heat application before reperfusion following ischemia(PreHeat), 3) heat application after reperfusion following ischemia(PostHeat). All groups were 30 minute, 1 hour, 3 hours reperfusion after 2 hours ischemia with clamping abdominal artery, and investigate superoxide dismutase(SOD) immunohistochemical reactions for quadriceps femoris muscle of the rat. SOD immunohistochemical reaction of experimental groups were more than the control group.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.4
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• pp.319-324
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• 2000

The causal relationship between heat shock protein (HSP) and second window of cardioprotective effect is still undetermined. In the present study, we assessed whether HSP-producing substances, amphetamine and ketamine, afforded protection against reperfusion-induced ventricular fibrillation (VF) and these protective effect remained after the inhibition of HSP72 production by quercetin, a mitochondrial ATPase inhibitor. Adult mongreal male cats $(n=60,\;2.5{\sim}4\;kg)$ were used in this study. Experimental animals were divided into five groups; control group (n=15), amphetamine ('A', n=11) group, ketamine ('K', n=9) group, amphetamine-ketamine ('AK', n=16) group and amphetamine-ketamine-quercetin ('AKQ', n=9) group. Twenty-four hours after the drug treatment, an episode of 20-min coronary artery occlusion was followed by 10-min reperfusion. The incidence of reperfusion-induced VF in the AK and AKQ groups was significantly lower than that in control group (p＜0.01). After the ischemia/reperfusion procedure, western blot analysis of HSP72 expression in the myocardial tissues resected from each group was performed. HSP72 production in the AK group was marked, whereas HSP72 was not detected in the AKQ and control groups. These results suggest that the suppressive effect against reperfusion-induced VF induced by amphetamine and ketamine is not mediated by myocardial HSP72 production but by other mechanisms.

• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.46-54
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• 2000

Objectives : Talmyung-san(TMS) has been used for treatment of brain diseases in Chinese traditional medicine. However, little is known about the mechanism by which TMS rescues brain cells from ischemic damages. To elucidate the protective mechanisms of TMS, we execute experiments. Methods : The effects of TMS on ischemia/reperfusion-induced cytotoxicity and generation of nitric oxide(NO) are investigated in primary neonatal myocardial cells and A7rS, aortic smooth muscle cell line. Results : Ischemia/reperfusion itself induces severe myocardial cell death in vitro. However, treatment of the cells with TMS significantly reduces both ischemia/reperfusion-induced myocardial cell death and LDH release. In addition, pretreatment of TMS before reperfusion recovers the lose of beating rates alter ischemia/reperfusion. For a while, the water extract of TMS stimulates myocardial cells to produce NO in a dose dependent manner and it protects the damage of ischemia/reperfusion-induced myocardial cells. Furthermore, the protective effects of the water extract of TMS is mimicked by treatment of sodium nitroprusside, an exogenous NO donor. NG-monomethyl-L-arginine (NGMMA), a specific inhibitor of nitric oxide synthase(NOS), significantly blocks the protective effects of TMS on the cells after ischemia/reperfusion. In addition, on ischemia the water extract of TMS induce NO in A7r5 cell. Conclusions : Taken together, we suggest that the protective effects of TMS against ischemia/reperfusion-induced myocardial damages may be mediated by NO production of myocardial and vascular smooth muscle cell during ischemic condition.

• Journal of Korean Neurosurgical Society
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• v.38 no.3
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• pp.221-226
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• 2005

Objective : Reactive oxygen metabolites and polymorphonuclear leukocytes have been implicated in the pathophysiology of reperfusion injury. The mechanisms involved in superoxide-mediated leukocyte adherence remain unclear, however, nitric oxide[NO] may contribute to this response. The present study is undertaken to elucidate mechamisms controlling NO based mechanisms that regulated leukocyte-endothelial interactions in the cerebral vasculature after global cerebral ischemia and reperfusion. Methods : Pial venular leukocyte adherence of anesthetized newborn piglets was quantified by in situ fluorescence videomicroscopy through closed cranial windows during basal conditions and during 2hours of reperfusion after global ischemia induced by 9minutes of asphyxia. Nitric oxide synthase[NOS] was inhibited by local window superfusion of L-nitroarginine[NA]; superfusion of sodium nitroprusside[SNP] was used to donate NO. Results : The mean number of adherent leukocytes to cerebral venules in the 9minutes asphyxia and 2hours reperfusion group were $161{\pm}19$ compared with $13{\pm}4$ in the nonasphyxial group. Superfusion of L-NA through the cranial window for 2hours resulted in leukocyte adherence similar to that observed during the initial 2hours of reperfusion after asphyxia. Leukocyte adherence was not additionally increased in asphyxic animal treated with L-NA. SNP inhibited asphyxia induced leukocyte adherence back to control levels. Conclusions : Nitric oxide inhibits leukocyte adherence to cerebral venules during the initial hours of reperfusion after asphyxia, and that NO supplementation inhibit asphyxia induced leukocyte adherence back to control levels. These results indicate that NO is an important factor in ischemia-reperfusion induced leukocyte adherence.

• Archives of Pharmacal Research
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• v.23 no.6
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• pp.620-625
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• 2000

The mechanisms of liver injury from cold storage and reperfusion are not completely under-stood. The aim of the present study was to investigate whether the inactivation of Kupffer cells (KCs) by gadolinium chloride ($GdCl_3$) modulates ischemia-reperfusion injury in the rat liver. Hepatic function was assessed using an isolated perfused rat liver model. In livers subjected to cold storage at $4^{\circ}C$ in University of Wisconsin solution for 24 hrs and to 20 min rewarm-ing ischemia, oxygen uptake was markedly decreased, Kupffer cell phagocytosis was stimulated, releases of purine nucleoside phosphorylase and lactate dehydrogenase were increased as compared with control livers. Pretreatment of rats with $GdCl_3$) , a selective KC toxicant, suppressed kupffer cell activity, and reduced the grade of hepatic injury induced by ischemia-reperfusion. While the initial mixed function oxidation of 7-ethoxycoumarin was not different from that found in the control livers, the subsequent conjugation of its meta-bolite to sulfate and glucuronide esters was suppressed by ischemia-reperfusion, CdCl$_3$restored sulfation and glucuronidation capacities to the level of the control liver. Our findings suggest that Kupffer cells could play an important role in cold/warm ischemia-reperfusion hepatic injury.

• Journal of Veterinary Clinics
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• v.6 no.2
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• pp.269-279
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• 1989

The incidence of reperfusion arrhythmia(RA) according to occlusive position of coronary artery was induced in 25 open-chest dogs anestherized with halothan, these were ligated between anterior ventricular branch and marginal branch of left circumflex artery for 30 minutes and after releasing of the ligation, the incidence of RA was observed during 5 minutes. The incidence rate of RA occurred in 36％(9 heads) of the cases, 20%(5 heads) of them died before reperfusion and 44％(11 heads) of them survived after reperfusion. In the classification according to the length of anterior ventricular branch in left circumflex artery, the incidence rate of RA occurred in 80％ of the group I(5 heads) which belongs to short size of anterior ventricilar branch, in 50% of the group II (8 heads) which belongs to medium size, in 8.3% of the group III(12 heads) which belongs to long size and in 61.5% of the groups I and II(13 heads). These results showed the higher incidence rate of RA than in other occlusive position (left anterior descending artery), and it may be estimated that the incidence of RA changed with the significant difference according to the lengthe of anterior ventricular branch, in other words, dimension of ischemic area in left ventricle.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.4
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• pp.287-294
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• 2006

Vascular thrombosis and ischemic necrosis still remain the most significant threats to the survival of free flaps. To date, neutrophils have been implicated in the pathogenesis of postischemic injury. Several studies have demonstrated that modulating the neutrophil response to ischemia-reperfusion injury can decrease the extent of the injury. In addition, some authors noticed that mast cell counts were also increased in flaps exposed to state of ischemia/reperfusion. So, we designed to evaluate the role of mast cells in ischemia/reperfusion by blocking histamine and to compare the effect of L-arginine, a nitric oxide precursor which is known to prevent neutrophil-mediated tissue injury. Epigastric island skin flaps were elevated in 30 rats and rendered ischemic. Thirty minutes prior to reperfusion, the rats were treated with intraperitoneal saline, diphenhydramine, cimetidine, and L-arginine. The necrosis rate of flap at 7 days, the number of neutrophils and mast cells at 20 hours were evaluated. In conclusion, histamine receptor blockers as well as L-arginine significantly decreased flap necrosis in a rat skin island ischemia-reperfusion flap model, but the protective effect was not significantly different in both agent groups.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.97-97
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• 1997

It was reported that ATP depletion occurs and accelerates cell damage during ischemia and reperfusion. To determine the mechanism of cell damage, the change of energy metabolism in liver was studied during ischemia/reperfusion. The groups were divided into four categories : sham-operated group, ischemia/reperfusion group, and two types of ATP-MgCl$_2$ treatment groups(one was treated during ischemia and the another during reperfusion). Rats were administered intravenously saline or ATP-MgCl$_2$. Rats were anesthetized and blood vessels in the left and median lobes of the liver were occluded. After 60min of ischemia, the clamp at those vessels were removed. After ischemia, one and five hours after reflow, energy metabolites(ATP, ADP, AMP, inosine, adenosine, hypoxanthine, xanthine) in liver were measured with HPLC. To observe mitochondrial function, aterial keton body ratio in blood and mitochondrial glutamate dehydrogenase activity in liver were measured. And lipid peroxidation was measured to evalutate the involvement of free radicals. In this study, ATP and ADP were catabolized to their metabolites(AMP, inosine, adenosine, hypoxanthine, xanthine) during ischemia and they resynthesized ATP and ADP during reperfusion. But total purine base were not restored to level of normal rat. The main source of resynthesizing ATP and ADP was AMP. In both ATP-MgCl$_2$ treated groups, mitochondrial function was protected and lipid peroxidation was significantly reduced. Our findings suggest that ischemia/reperfusion impairs hepatic energy metabolism.