• Archives of Reconstructive Microsurgery
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• v.21 no.1
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• pp.61-67
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• 2012

Purpose: The purpose of this study was to investigate the role of mast cells and their product, histamine and leukotriene in ischemia-reperfusion injury. Methods: Forty Sprague-Dawley rats were divided into four groups. (Group I: Control group without ischemia, Group II: Normal saline with ischemia, Group III: Cimetidine with ischemia, Group IV: Zafirlukast with ischemia) Skin flap was elevated and ischemic insult was given by clamping the artery for 12 hours. Before reperfusion, the rats were treated with saline, cimetidine and zafirlukast. Flap survival was evaluated at 7 days. Neutrophil counts, mast cell counts were evaluated 24 hours after reperfusion. Results: Flap survival rate in the control group was 92.33%, whereas normal saline group had 37.34% survivals. Cimetidine and zafirlukast treated group showed significantly higher survival rates than normal saline group. The neutrophil and mast cell counts in cimetidine and zafirlukast treated group were significantly decreased than normal saline group. Cimetidine treated group showed higher survival rate and lower cell counts than zafirlukast treated group. Conclusion: The administration of cimetidine and zafirlukast can decrease neutrophils and mast cells caused by ischemia-reperfusion and increase flap survivals. It is suggests that antihistamine and leukotriene receptor antagonist have protective effect against ischemia-reperfusion injury to skin flap in rat.

• Journal of Trauma and Injury
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• v.29 no.4
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• pp.204-208
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• 2016

For an orthopaedic surgeon, the critical decisions to either amputate or salvage a limb with severe crushing injury with progressive ischemic change due to arterial rupture or occlusion can become a clinical dilemma at the Emergency Department (ED). And reperfusion injury is one of the fetal complications after vascular reconstruction. The authors present a case which was able to save patient's life by rapid vessel ligation at bedside to prevent severe reperfusion injury. A 43-year-old male patient with no pre-existing medical conditions was transported by helicopter to Level I trauma center from incident scene. Initial result of extended focused assessment with sonography for trauma (eFAST) was negative. The trauma series X-rays at the trauma bay of ED showed a multiple contiguous rib fractures with hemothorax and his pelvic radiograph revealed a complex pelvic trauma of an Anterior Posterior Compression (APC) Type II. Lower extremity computed tomography showed a discontinuity in common femoral artery at the fracture site and no distal run off. Surgical finding revealed a complete rupture of common femoral artery and vein around the fracture site. But due to the age aspect of the patient, the operating team decided a vascular repair rather than amputation even if the anticipated reperfusion time was 7 hours from the onset of trauma. Only two hours after the reperfusion, the patient was in a state of shock when his arterial blood gas analysis (ABGA) showed a drop of pH from 7.32 to 7.18. An imminent bedside procedure of aseptic opening the surgical site and clamping the anastomosis site was taken place rather than undergoing a surgery of amputation because of ultimately unstable vital sign. The authors would like to emphasize the importance of rapid decision making and prompt vessel ligation which supply blood flow to the ischemic limb to increase the survival rate in case of profound reperfusion injury.

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.201-209
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• 1996

Restoration of the blood flow after a period of ischemia is accompanied by generation of toxic oxygen radicals. This phenomenon may account for the occurrence of reperfusion-mediated tissue injury in ischemic hearts. In in vitro studies, although oxygen radicals can be generated from a variety of sources, including xanthine oxidase system, activated leucocytes, mitochondria and others, the most important source and mechanism of oxygen radical production in the post-ischemic reperfused hearts is unclear. In the present study, we tested the hypothesis that the respiratory chain of mitochondria might be an important source of oxygen radicals which are responsible for the development of the reperfusion injury of ischemic hearts. Langendorff-perfused, isolated rat hearts were subjected to 30 min of global ischemia at $37^{\circ}C$, followed by reperfusion. Amytal, a reversible inhibitor of mitochondrial respiration, was employed to assess the mitochondrial contributions to the development of the reperfusion injury. Intact mitochonria were isolated from the control and the post-ischemic reperfused hearts. Mitochondrial oxygen radical generation was measured by chemiluminescence method and the oxidative tissue damage was estimated by measuring a lipid peroxidation product, malondialdehyde(MDA). To evaluate the extent of the reperfusion injury, post-ischemic functional recovery and lactate dehydrogenase(LDH) release were assessed and compared in Amytal-treated and -untreated hearts. Upon reperfusion of the ischemic hearts, MDA release into the coronary effluent was markedly increased. MDA content of mitochondria isolated from the post-ischemic reperfused hearts was increased to 152% of preischemic value, whereas minimal change was observed in extramitochondrial fraction. The generation of superoxide anion was increased about twice in mitochondria from the reperfused hearts than in those from the control hearts. Amytal inhibited the mitochondrial superoxide generation significantly and also suppressed MDA production in the reperfused hearts. Additionally, Amytal prevented the contractile dysfunction and the increased release of LDH observed in the reperfused hearts. In conclusion, these results indicate that the respiratory chain of mitochondria may be an important source of oxygen radical formation in post-ischemic reperfused hearts, and that oxygen radicals originating from the mitochondria may contribute to the development of myocardial reperfusion injury.

• 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.

• 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 Yeungnam Medical Science
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• v.41 no.2
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• pp.61-73
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• 2024

Acute kidney ischemia-reperfusion (IR) injury is a life-threatening condition that predisposes individuals to chronic kidney disease. Since the kidney is one of the most energy-demanding organs in the human body and mitochondria are the powerhouse of cells, mitochondrial dysfunction plays a central role in the pathogenesis of IR-induced acute kidney injury. Mitochondrial dysfunction causes a reduction in adenosine triphosphate production, loss of mitochondrial dynamics (represented by persistent fragmentation), and impaired mitophagy. Furthermore, the pathological accumulation of succinate resulting from fumarate reduction under oxygen deprivation (ischemia) in the reverse flux of the Krebs cycle can eventually lead to a burst of reactive oxygen species driven by reverse electron transfer during the reperfusion phase. Accumulating evidence indicates that improving mitochondrial function, biogenesis, and dynamics, and normalizing metabolic reprogramming within the mitochondria have the potential to preserve kidney function during IR injury and prevent progression to chronic kidney disease. In this review, we summarize recent advances in understanding the detrimental role of metabolic reprogramming and mitochondrial dysfunction in IR injury and explore potential therapeutic strategies for treating kidney IR injury.

• The Korean Journal of Pain
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• v.21 no.2
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• pp.119-125
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• 2008

Background: Cerebral blood vessels are innervated by sympathetic nerves from the superior cervical ganglia (SCG), and these nerves may influence the cerebral blood flow. The purpose of the present study was to evaluate the neuroprotective effect of superior cervical sympathetic ganglion block in rats that were subjected to focal cerebral ischemia/reperfusion injury. Methods: Eighty male Sprague-Dawley rats (270-320 g) were randomly assigned to one of two groups (the ropivacaine group and a control group). In all the animals, brain injury was induced by middle cerebral artery (MCA) reperfusion that followed MCA occlusion for 2 hours. The animals of the ropivacaine group received $30{\mu}l$ of 0.75% ropivacaine, and their SCG. Neurologic score was assessed at 1, 3, 7 and 14 days after brain injury. Brain tissue samples were then collected. The infarct ratio was measured by 2.3.5-triphenyltetrazolium chloride staining. The terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeled (TUNEL) reactive cells and the cells showing caspase-3 activity were counted as markers of apoptosis at the caudoputamen and frontoparietal cortex. Results: The death rate, the neurologic score and the infarction ratio were significantly less in the ropivacaine group 24 hr after ischemia/reperfusion injury. The number of TUNEL positive cells in the ropivacaine group was significantly lower than those values of the control group in the frontoparietal cortex at 3 days after injury, but the caspase-3 activity was higher in the ropivacaine group than that in the control group at 1 day after injury. Conclusions: The study data indicated that a superior cervical sympathetic ganglion block may reduce the neuronal injury caused by focal cerebral ischemia/reperfusion, but it may not prevent the delayed damage.

• 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.

• Korean Journal of Plant Resources
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• v.30 no.6
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• pp.647-653
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• 2017

Hepatic ischemia-reperfusion injury (HIRI) is linked with high mortality rate. Several agents have been developed so far to reduce the risk of HIRI. In this study, we investigated the effects of Acanthopanax senticosus extract (AS) on hepatic ischemia-reperfusion. To explore the protective effects of A. senticosus extract injection (ASI) on hepatic ischemia-reperfusion injury rats animal model were used. After the development of HIRI by using clamping method rats were then randomly divided into five groups. Different doses of AS were administered in HIRI rat model. The level of ALT, AST, and MDA content in serum were detected in sham and HIRI groups. The activity of SOD, MPO and $Ca^{2+}-ATPase$, content of MDA, and cAMP in hepatic tissue were also measured. Expression of Bcl-2 and Bax protein were detected by immunohistochemical staining method. Compared with sham group, ASI has the protective effect on the HIRI model in rats. Blood levels of ALT, AST, SOD, MPO, and MDA were significantly lower in ASI group compared with HIRI. Indeed SOD and $Ca^{2+}-ATPase$ activities, MDA content, and cAMP level were improved in ASI group. Furthermore, Bcl-2 and Bax protein were improved in ASI group compared with only HIRI group. These results suggest that AS may provide potential ameliorative therapy by inhibiting the damage signaling mechanism in hepatic ischemia/reperfusion injury model.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.5
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• pp.259-266
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• 2011

The aim of this study was to evaluate the preventive role of epigallocatechin-3 gallate (EGCG, a derivative of green tea) in ischemia/reperfusion (I/R) injury of isolated rat hearts. It has been suggested that EGCG has beneficial health effects, including prevention of cancer and heart disease, and it is also a potent antioxidant. Rat hearts were subjected to 20 min of normoxia, 20 min of zero-flow ischemia and then 50 min of reperfusion. EGCG was perfused 10 min before ischemia and during the whole reperfusion period. EGCG significantly increased left ventricular developed pressure (LVDP) and increased maximum positive and negative dP/dt (+/-dP/dtmax). EGCG also significantly increased the coronary flow (CF) at baseline before ischemia and at the onset of the reperfusion period. Moreover, EGCG decreased left ventricular end diastolic pressure (LVEDP). This study showed that lipid peroxydation was inhibited and Mn-SOD and catalase expressions were increased in the presence of EGCG. In addition, EGCG increased levels of Bcl-2, Mn-superoxide dismutase (SOD), and catalase expression and decreased levels of Bax and increased the ratio of Bcl-2/Bax in isolated rat hearts. Cleaved caspase-3 was decreased after EGCG treatment. EGCG markedly decreased the infarct size while attenuating the increase in lactate dehydrogenase (LDH) levels in the effluent. In summary, we suggest that EGCG has a protective effect on I/R-associated hemodynamic alteration and injury by acting as an antioxidant and anti-apoptotic agent in one.