• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.82-82
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• 1993

허혈-재관류손상 심근세포의 DNA에서 8-hydroxydeoxyguanosine (8-OHdG) 생성을 검토하였다. 흰쥐 적출심장의 Langendorff 관류 표본에서 대동맥 차단에 의한 60분 허혈후 산소가 포화된 Kredb-Henseleit용액으로 30분간 재관류 하므로서 허혈-재관류 손상을 유도하였다. 재관류 후 심근세포에서 DNA를 추출하고 HPLC(EC detector)를 이용하여 8-OHdG를 측정하였다. 실험결과 허혈-재관류 심근세포의 DNA에서 8-OHdG 함량이 증가하였으며 이는 $O_2$ 제거물질인 superoxide dismutase와 OH 제거물질인 mannitol에 의하여 방지되었다. Xanthine oxidase외 경쟁적 길항약인 allopurinol도 8-OHdG 생성을 억제하였으며 단백분해효소 억제제인 phenylsulfonylfluoride 그리고 관류액에서 칼슘의 제거 또한 허혈-재관류 심근 DNA의 생성을 방지하였다. 이상의 결과 허혈심근의 재관류시 8-OHdG 생성이 증가하며 이는 재관류 손상과 같은 산화성 심근손상을 평가하는 좋은 Index가 될 수 있을 것으로 여겨진다.

• Journal of Veterinary Clinics
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• v.26 no.5
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• pp.441-444
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• 2009

Ischemia-reperfusion (I/R) injury is associated with an increased risk of acute rejection, delayed graft function and long-term changes after kidney transplantation. The reperfusion models remain unsolved complications such as vascular obstruction and blood leakage. We developed an alternative model of isolated hemoperfusion in porcine kidneys. In the present study we introduced a newly developed reperfusion method. A connector was used instead of surgical suture for the vascular anastomosis on the inguinal region in which main femoral vessels are parallel and big enough to perfuse the kidney. To assess renal perfusion quality of the modified hemoreperfusion model, we analyzed both hemodynamic values and patterns of I/R injury following a renal reperfusion. Following unilateral nephrectomy, the kidneys were preserved for 0, 24 and 48 hours at $4^{\circ}C$ with histidine-tryptophan ketogluatarate (HTK) solution and reperfused for 3 hours by vascular anastomosis connected to the femoral artery and vein in inguinal region. Histolopathological examinations were assessed on kidney biopsy specimens, taken after each cold storage and reperfusion. No differences of hemodynamic values were observed between aorta and femoral artery. The average warm ischemia time before reperfusion start was $7.0{\pm}1.1$ minutes. There were no complications including vascular obstruction and blood leakage during the reperfusion. I/R injury of the perfused kidneys in this model was dependent upon the cold ischemia time. The results support that the modified perfusion model is simple and appropriate for the study of early renal I/R injury and transplant immunology.

• Journal of Chest Surgery
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• v.35 no.2
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• pp.87-93
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• 2002

Background: Predicting the important role of intercellular adhesion molecule-1 expression on the acute ischemia-reperfusion injury, we set out to demonstrate it by assessing the degree of expression of ICAM-1 after warm ischemia-reperfusion in canine unilateral lung ischemia model. Material and Method: Left unilateral lung ischemia was induced by clamping the left hilum for 100 minutes in seven adult mongrel dogs. After reperfusion, various hemodynamic pararmeters and blood gases were analyzed for 4 hours, while intermittently clamping the right hilum in order to allow observation of the injured Ieft lung function. The pulmonary venous blood was collected serially to measure TNF- and cICAM-1 level. After 4 hours of reperfusion, the lung tissue was biopsied to assess cICAM-1 expression, and to measure tissue malondialdehyde(MDA) and ATP level. Result: The parameters including arterial oxygen partial pressure, pulmonary vascular resistance and tissue MDA and ATP level suggested severe lung damage. Serum TNF-$\alpha$ level was 8.76$\pm$2.37 ng/ml at 60 minutes after reperfusion and decreased thereafter. The cICAM-1 level showed no change after the reperfusion during the experiment. The tissue cICAM-1 expression was confirmed in 5 dogs. Conclusion: The increase of TNF-$\alpha$ Ievel and expression of tissue ICAM-1 were demonstrated after ischemia reperfusion injury in canine lung model.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.205-205
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• 1996

본 실험은 간장허혈 및 재관류시 야기되는 간장 손상에 대해 vitamin C와 E 각각의 효과와 이들의 병용효과를 알아보고자 하였다. 실험군은 흰쥐에 vitamin E(25mg/kg)를 실험전 3일간 투여한 군, vitamin C(100mg/kg)를 실험 5분전 경정맥주사한 군 및 vitamin C와 E의 병용 투여군등의 3군으로 하여 각각에 허혈을 유발시킨 후 (60분) 재관류 1시간, 5시간에 간세포 손상정도(AI.T, AST, liver wet-weight to dry-weight ratio), 지질과산화(MDA), 담즙분비변동(bile flow, bilirubin, cholate output) 및 약물대사효소계의 변동(cytochrome P$_{450}$, aminopyrine-N-demethylase, aniline p-hydroxylase activity) 등을 관찰하였다. 실험결과로는 허혈 및 재관류로 인한 ALT, AST MDA는 재관류 5시간에 최고치를 이루었으며 이는 vitamin C와 vitamin E의 각각 투여로 억제되었고, 특히 vitamin C와 E의 병용투여로 더욱 현저하게 억제되었다. 간세포 부종의 지표인 liver wet-weight to dry-weight ratio도 vitamin C와 E의 병용투어로 유의성있게 억제되었다. 담즙분비량 및 담즙산량은 vitamin C 투여와 vitamin C와 E 병용투여로 허혈 및 재관류로 감소된 양을 증가시켰고, 특히 vitamin C와 E의 병용투여는 담즙분비량에 있어 현저한 상승을 나타내었다. 허혈 및 재관류로 인한 cytochrome P$_{450}$양의 감소와 aminopyrine N-demethylase 활성의 억제는 vitamin C 투여와 vitamin C와 E의 병용투여에 의해 유의성 있게 증가하였다. 이상의 결과로 보아 vitamin C와 vitamin E는 각각 허혈 및 재관류로 인한 간장손상을 완화시켰으며 특히 vitamin C와 E의 병용투여는 상승적으로 적용하여 간세포손상을 더욱 억제시킴을 알 수 있었다.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.3
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• pp.370-378
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• 2019

The hepatic ischemic model has recently been widely used for the epidemiological study of ischemic reperfusion injury. This study was carried out to investigate the protective effect of vanillin, which is known to have antioxidant and anti-inflammatory effects, against hepatic and renal injury using an ischemia-reperfusion rat model, and we also investigated the mechanism related to vanillins' protective effect. The test material was administered at a concentration of 100 mg/kg for 3 days, followed by ligation of the liver for 60 minutes to induce ischemia reperfusion. As control groups, there was a negative control, sham control and ischemia-reperfusion-only ischemia reperfusion control, and the controls groups were compared with the drug administration group. In the vanillin group, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly inhibited compared with the AST and ALT activities of the ischemia-reperfusion group, and histopathological examination showed significant reduction of both inflammation and necrosis. The malondialdehyde (MDA) and superoxide dismutase (SOD) levels were significantly different from the ischemia-reperfusion group. In conclusion, vanillin showed a hepatocyte protective action by alleviating the cellular inflammation and cell necrosis caused by hepatic ischemia-reperfusion, and vanillin mitigated inflammatory changes in the kidney glomeruli and distal tubules. The protective effect is considered to be caused by vanillin's antioxidant function. Further studies such as on cell death and possibly vanillin's same effect on damaged tissue will be necessary for clinical applications such as organ transplantation.

• Journal of Veterinary Clinics
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• v.25 no.4
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• pp.257-262
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• 2008

Renal ischemia-reperfusion injury is great clinical important because viability of the transplanted organ depends on the tolerance of the graft to ischemia-reperfusion injury, an inevitable processing during surgery. The purpose of this study was to investigate the effects of irrigation-aspiration in ischemia-reperfusion injury model induced by cross-clamping of renal vessels. Blood samples were collected from these dogs for measurement of kidney function and antioxidant enzyme activity, and RI at the intrarenal artery was measured at different time intervals. And the kidneys were taken for histopathologic evaluation at day 14. Kidney function (Cr and BUN) showed a significant increasing in untreated group compared to treated group. Resistive index of intrarenal artery was no significant difference among the groups. Activity of antioxidant enzymes in plasma was significant decrease in untreated group compare to control group while in treated group was no significant difference compared to control group. In histopathologic finding, treated group was showed less damage than that of untreated group. This result suggests that the processing of irrigation-aspiration is useful to reducing ischemia-reperfusion injury.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.1-8
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• 1993

To elucidate involvement of platelet-activating factor (PAF) in cerebral ischemia-reperfusion injury, male Sprague-Dawley rats and albino mice of either sex were subjected to a 10-min bilateral carotid artery occlusion and 6-hr recirculation. The McGraw stroke index in mice was markedly inhibited by PAF antagonists, BN 52021 and CV 6209 (1 mg/kg, i.p., each) When they were administered 10 min before bilateral carotid artery occlusion or 1 hr after reperfusion. The increases in brain water content were significantly attenuated by treatment with BN 52021 or CV 6209 in both animals. BN 52021 exhibited a significant improvement in the postischemic blood pressure change in association with a beneficial effect on the delayed dilatation of pial arterioles after 10 min of ischemia. Thus it is suggested that PAF plays an important role as an endogenous mediator in development of cerebral ischemia-reperfusion injury, and further, specific antagonists to PAF will be able to prevent or reverse the pathological sequelae of cerebral ischemia.

• Journal of Chest Surgery
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• v.29 no.8
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• pp.807-815
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• 1996

The protective effect of'ischemic preconditioning'on ischemid-reperfusion injury of heart has been reported in various animal species. but without known mechAnism in detail, In An attempt to investigate the cardioprotective mechanism of ischemic preconditioning, we examined the effects of nitric oxide(UO) synthesis in preconditioned heart of rat The isolated hearts perfused by Langendorfr's method were ex- posed to 30min global ischemia followed by 30min reperfusion with oxygenated Krebs-Henseleit(K-H) sol- ution. Ischemic preconditioning was performed with three episodes of Sm n ischemia and Smin repeyfusion before the induction of prolong ischemia(30min)-reperfusion(30min). Ischemic preconditioning prevented the depression of cardiac function(left ventricular pressure .K heart rate) observed in the ischemia- reperfusion hearts and reduced the release of lactate dehydrogenase during the reperfusion period. On electromicroscopic pictures, myocardial ultrastructures wore relatively well preserved in isthemic preconditioned hearts. N6_nitro-L-arginine methyl ester(L-NAME) an inhibitor of L-arginine citric oxide pathway, was infused at a rate O.Smllmin In a dose of 10mg kg-1 before the initial ischemic preconditioning. neither the protection of cardiac function nor the reduction of LDH releAse in ischemic preconditioning hearts was altered in the presence of added L-NAME On ultrastructural finding, the preservation of morphology in ischemic preconditioning heart was not change by the pretreatment of L-UAME. The failure of the WO synthesis inhibitor to reduce t e effect of ischemic preconditioning may be related to be species specific in that NO may allot be the trigger for ischemic preconditioning in rats.

• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.163-170
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• 1992

The present study was attempted to investigate the effect of cyclobuxine (a steroidal alkaloid) on generation of reactive oxygen metablite and myocardial damage promoted by an exogenous administeration of arachidonate in ischemic-reperfused hearts. Langendorff preparation of the isolated rat heart was made ischemic condition by reducing the flow rate to 0.5 ml/min for 45 min, and then followed by normal reperfusion (7 ml/min) for 5 min. The generation of superoxide anion was estimated by measuring the SOD-inhibitable ferricytochrome C reduction. The degree of lipid peroxidation in myocardial tissue was estimated from the tissue malondialdehyde (MDA) concentration using thiobarbituric acid method. The myocardial cell damage was observed by measuring LDH released into the coronary effluent. Sodium arachidonate $(0.1\;and\;1.0\;{\mu}g/ml)$ infused during the period of oxygenated reperfusion stimulated superoxide anion production dose-dependently. The rate of arachidonate-induced superoxide anion generation was markedly inhibited by cyclobuxine $(1.0\;and\;10\;{\mu}g/ml)$. The production of malondialdehyde was increased by infusion of arachidonate. This increase was prevented by superoxide dismutase (300 U/ml) and cyclobuxine $(1.0\;and\;10\;{\mu}g/ml)$. The release of LDH was increased by sodium arachidonate was also inhibited by superoxide dismutase and cyclobuxine. In conclusion, the present results suggest that cyclobuxine inhibits the production of reactive oxygen metabolite and myocardial damages which were promoted by an administeration of arachidonate during reperfusion of ischemic hearts.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.321-330
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• 1994

The protective effect of 'ischemic preconditioning (PC)' on ischemia-reperfusion injury of heart has been reported in various animal species, but without known mechanisms in detail. In an attempt to investigate the cardioprotective mechanism of PC, we examined the effects of PC on the myocardial oxidative injuries and the oxygen free radical production in the ischemia-reperfusion model of isolated Langendorff preparations of rat hearts. PC was performed with three episodes of 5 min ischemia and 5 min reperfusion before the induction of prolonged ischemia (30 min)-reperfusion(20 min). PC prevented the depression of cardiac function (left ventricular pressure x heart rate) observed in the ischemic-reperfused heart, and reduced the release of lactate dehydrogenase during the reperfusion period. On electron microscopic pictures, myocardial ultrastructures were relatively well preserved in PC hearts as compared with non-PC ischemic-reperfused hearts. In PC hearts, lipid peroxidation of myocardial tissue as estimated from malondialdehyde production was markedly reduced. PC did not affect the activity of xanthine oxidase which is a major source of oxygen radicals in the ischemic rat hearts, but the myocardial content of hypoxanthine (a substrate for xanthine oxidase) was much lower in PC hearts. It is suggested from these results that PC brings about significant myocardial protection in ischemic-reperfused heart and this effect may be related to the suppression of oxygen free radical reactions.