• Advances in Traditional Medicine
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• v.9 no.1
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• pp.67-73
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• 2009

Temporary clamping of the portal triad is a common strategy to minimize bleeding during liver transplantation. Increasing evidences suggests that oxygen derived free radicals and reintroduction of oxygen in ischemic tissue lead to ischemic and reperfusion injury (I/R) and lead to apoptosis and necrosis. Adult Wistar rat subjected to 60 min of partial liver ischemia followed by three hour reperfusion. Eighteen Wister rats were divided into sham-operated control group (I) (n = 6), ischemia and reperfusion group (II) (n = 6), folic acid treated group (1 mg/kg body weight/daily by oral route for 7 days before induced ischemia reperfusion maneuver) (III) (n = 6). Apoptotic and necrotic hepatocytes, mitochondrial antioxidant enzymes were measured. Liver injury was assessed by alanine transaminases (ALT), aspartate transaminases (AST), liver histopathology and electron microscopy. An ischemic and reperfusion hepatocellular injury was indicated by increased serum-ALT, AST, histopathology and electron microscopy studies. Apoptotic and necrotic cells were increased which was revealed by flow cytometry in I/R group. Pre- treatment with folic acid significantly decreased serum -ALT, AST levels, apoptotic and necrotic cells after 1 h ischemia followed by 3 h of reperfusion. Histopathology and TEM studies showed markedly diminished hepatocellular injury in folic acid pretreated rats during the hepatic I/R, which reached a level comparable to saline-treated rat of sham operated group. On the basis of our findings it may be concluded that folic acid afforded significant protection from necrosis and apoptosis in I/R injury.

• Archives of Plastic Surgery
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• v.33 no.6
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• pp.742-747
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• 2006

Purpose: The purpose of this study was to evaluate the role of mast cell and histamine as typical product of mast cell in ischemia-reperfusion injury of muscle flap using H2 receptor blocker and mast cell stabilizer. Methods: Thirty-five Sprague-Dawley rats weighing 250-300 gm were divided into four groups; Group I: Control group without ischemia, Group II: Normal saline injection group with ischemia, Group III: Cimetidine injection group with ischemia, Group IV: Sodium cromoglycate injection group with ischemia. Well established single pedicled transverse rectus abdominis musculocutaneous(TRAM) flap was designed in all rats and were rendered ischemia by clamping the artery for 150 minutes. All injections were applied intramuscular around gluteal area 30 minutes before reperfusion. The flap survival was evaluated at 7 days after operation. Neutrophil counts and mast cell counts were evaluated 24 hours after reperfusion. Results: The difference of skin flap survival between control group and cimetidine injection group was not significant. In the normal saline injection group flap survival was markedly decreased compared to that of control group. The muscle flap survival was similar to the results of skin flap survival. The neutrophil counts were significantly decreased in control group and sodium cromoglycate injection group than normal saline injection group. The mast cell counts were significantly decreased in cimetidine injection group and control group than both normal saline injection and sodium cromoglycate injection groups. The protective effect of sodium cromoglycate was not seen in the skin flap, but the muscle flaps showed protective effects of sodium cromoglycate compared to normal saline injection group. Conclusions: It is suggests that commonly used antihistamine(H2 receptor blocker) has protective effect against ischemia-reperfusion injury to skin and muscle flaps by reducing neutrophil and mast cell. The mast cell stabilizer was not effective for skin flap but, possibly, for muscle flap.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.2
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• pp.45-55
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• 2007

We elucidated the effects of various components of ischemic medium on the outcome of simulated ischemia-reperfusion injury. Hypoxia for up to 12 hours induced neither apoptotic bodies nor LDH release. However, reoxygenation after 6 or 12 hours of hypoxia resulted in a marked LDH release along with morphological changes compatible with oncotic cell death. H9c2 cells were then subjected to 6 hours of simulated ischemia by exposing them to modified hypoxic glucose-free Krebs-Henseleit buffer. Lowered pH (pH 6.4) of simulated-ischemic buffer resulted in the generation of apoptotic bodies during ischemia, with no concomitant LDH release. The degree of reperfusion-induced LDH release was not affected by the pH of ischemic buffer. Removal of sodium bicarbonate from the simulated ischemic buffer markedly increased cellular damages during both the simulated ischemia and reperfusion. Addition of lactate to the simulated ischemic buffer increased apoptotic cell death during the simulated ischemia. Most importantly, concomitant acidosis and high lactate concentration in ischemic buffer augmented the reperfusion-induced oncotic cell death. These results confirmed the influences of acidosis, bicarbonate deprivation and lactate on the progression and outcome of the simulated ischemia-reperfusion, and also demonstrated that concomitant acidosis and high lactate concentration in simulated ischemic buffer contribute to the development of reperfusion injury.

• 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.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.299.1-299.1
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• 2002

Failure of the hepatic microcirculation is a major component of reperfusion injury in the liver. However. the vasoactive mediators involved in the regulation of sinusoidal flow during reperfusion following hepatic ischemia remain to be identified. We investigate the role of Kupffer cells in hepatic ischemia/reperfusion (l/R)-induced imbalance of vasoregulatory gene expression. Rats were subjected to 60 min hepatic ischemia, followed by 5 h of reperfusion. (omitted)

• Archives of Pharmacal Research
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• v.28 no.12
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• pp.1392-1399
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• 2005

This study evaluated the effect of $\alpha$-tocopherol ($\alpha$-TC), ischemic preconditioning (IPC) or a combination on the extent of mitochondrial injury caused by hepatic ischemia/reperfusion (I/R). Rats were pretreated with $\alpha$-TC (20 mg/kg per day, i.p.) for 3 days before sustained ischemia. A rat liver was preconditioned with 10 min of ischemia and 10 min of reperfusion, and was then subjected to 90 min of ischemia followed by 5 h or 24 h of reperfusion. I/R increased the aminotransferase activity and mitochondrial lipid peroxidation, whereas it decreased the mitochondrial glutamate dehydrogenase activity. $\alpha$-TC and IPC individually attenuated these changes. $\alpha$-TC combined with IPC ($\alpha$-TC+IPC) did not further attenuate the changes. The mitochondrial glutathione content decreased after 5 h reperfusion. This decrease was attenuated by $\alpha$-TC, IPC, and $\alpha$-TC+IPC. The significant production of peroxides observed after 10 min reperfusion subsequent to sustained ischemia was attenuated by $\alpha$-TC, IPC, and $\alpha$-TC+IPC. The mitochondria isolated after I/R were rapidly swollen. However, this swelling rate was reduced by $\alpha$­TC, IPC, and $\alpha$-TC+IPC. These results suggest that either $\alpha$-TC or IPC reduces the level of mitochondrial damage associated with oxidative stress caused by hepatic I/R, but $\alpha$- TC combined with IPC offers no significant additional protection.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.199-199
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• 1998

In this study, the effects of ursodeoxycholic acid (UDCA) on ischemia/reperfusion injury were investigated on retrograded aortic perfusion model. Hearts from Sprague-Dawley rats were perfused with oxygenated Krebs-Henseleit solution (pH 7.4, 37) on a Langendorff apparatus. After equilibration, hearts were treated with ursodeoxycholic acid 10, 20, 40 and 800 M or vehicle (0.04% DMSO) for 10 min before the onset of ischemia. Following 25 min of global ischemia, ischemic hearts were reperfused and allowed to recover for 30 min. The physiological (i.e. heart rate, left ventricular diastolic pressure, coronary flow and time to contracture formation) and biochemical (lactate dehydrogenase, LDH) endpoints were evaluated. In vehicle group, time to contracture formation (TTC) value was 19.5 min during ischemia, LVDP was 20.8 mmHg at the endpoint of reperfusion and LDH activity in reperfusate was 59.7 U/L. Cardioprotective effects of UDCA following ischemia/reperfusion consisted of a reduced TTC (EC$\_$25/ = 16.10 M), reduced LDH release and enhanced recovery of contractile function during reperfusion. Especially, the treatments of UDCA 80 M remarkably increased LVDP (68.1 mmHg) and reduced LDH release (33.2 U/L). Our findings suggest that UDCA ameliorates ischemia/reperfusion-induced myocardial damage, in agreement with physiological and biochemical parameters.

• Journal of Korean Neurosurgical Society
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• v.30 no.1
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• pp.12-19
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• 2001

Objective : Albumin is a very useful drug for the improving of cerebral blood volume and the oncotic effect in cerebral ischemia or cerebral vasospasm. The purpose of this study was to examine the morphological and neurological effect of albumin therapy on reperfusion injury following transient focal cerebral ischemia. Materials and Methods : 18 Male Sprague-Dawley rats weighing 270-320g were used. The ischemia model was produced by 2-hour period of transient middle cerebral artery occlusion with a poly-L-lysin coated intraluminal suture. The agent(20% human serum albumin[HSA]) or control solution(NaCl 0.9%) was administered intravenously at a dosage of 1% of body weight immediate after reperfusion following a 2-hour period occlusion. Neurological function was evaluated by the postural reflex and the forlimb placing test during occlusion(at 60 min) and daily for 3 days thereafter. The brain was perfusion-fixed, and infarct volumes and brain edema were measured. Results : The HSA significantly improved the neurological score in treated group. The rats of albumin treatment group showed significantly reduced total infarct volume(by 34%) and brain edema(by 81%) compared with salinetreated rats. Conclusion : HSA showed a substantial effect on the transient focal cerebral ischemia and reperfusion injury model. These results may indicate its usefulness in treating reperfusion injury patients after thrombolysis treatment for the thrombo-embolic major cerebral artery occlusions.

• Journal of Ginseng Research
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• v.33 no.4
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• pp.283-293
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• 2009

Ginsenosides, one of the most well-known traditional herbal medicines, are used frequently in Korea for the treatment of cardiovascular symptoms. The effects of ginseng saponin on ischemia-induced isolated rat heart were investigated through analyses of hemodynamic changes including perfusion pressure, aortic flow, coronary flow, and cardiac output. Isolated rat hearts were perfused and then subjected to 30 min of global ischemia followed by 60 min of reperfusion with modified Kreb's Henseleit solution. Myocardial contractile function was continuously recorded. Ginseng saponin administered before inducing ischemia significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output. The ginseng saponin administered group significantly recovered all of the hemodynamic parameters, except heart rate, after ischemia-reperfusion (I/R) compared with ischemia control. The intracellular calcium ($[Ca^{2+}]_i$) content in rat neonatal cardiomyocytes was quantitatively determined. Administration of ginseng saponin significantly prevented $[Ca^{2+}]_i$ increase that had been induced by simulated I/R in vitro (p<0.01) in a dose-dependent manner, suggesting that the cardioprotection of ginseng saponin is mediated by the inhibition of $[Ca^{2+}]_i$ increase. Overall, we found that the administration of ginseng saponin has cardioprotective effects on the isolated rat heart after I/R injury. These results indicate that ginseng saponin has distinct cardioprotective effects in an I/R-induced rat heart.