• 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.

• Herbal Formula Science
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• v.29 no.1
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• pp.33-44
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• 2021

Renal ischemia-reperfusion injury(IRI), an important cause of acute renal failure (ARF), cause increased renal tubular injury. Jesaeng-sinkihwan (JSH) was recorded in a traditional Chines medical book named "Bangyakhappyeon (方藥合編)". JSH has been used for treatment of diabetes and glomerulonephritis with patients. Here we investigate the effects of Jesaeng-sinkihwan (JSH) in a mouse model of ischemic acute kidney injury. The animals model were divided into four groups at the age of 8 weeks; sham group: C57BL6 male mice (n=9), I/R group: C57BL6 male mice with I/R surgery (n=9), JSH Low group: C57BL6 male mice with surgery + JSH 100 mg/kg/day (n=9) and JSH High group: C57BL6 male mice with surgery + JSH 300 mg/kg/day (n=9). Ischemia was induced by clamping the both renal arteries during 25 min, and reperfusion was followed. Mouse were orally given with JSH (100 and 300 mg/kg/day during 3 days after surgery. Treatment with JSH significantly ameliorates creatinine clearance(Ccr), Creatinine (Cr) and blood urea nitrogen(BUN) in obtained plasma. . Treatment with JSH reduced kidney inflammation markers such as Neutrophil Gelatinase Associated Lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). JSH also reduced the periodic acid schiff (PAS) staining intensity and picro sirius red staining intensity in kidney of I/R group. These findings suggest that JSH ameliorates tubular injury including renal dysfunction in I/R induced ARF mouse.

• YAKHAK HOEJI
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• v.56 no.4
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• pp.260-267
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• 2012

This study examined the effects of baicalin, a bioactive flavonoid isolated from Scutellaria baicalensis, on hepatic injury caused by ischemia/reperfusion (I/R) in alcoholic fatty liver. Rats were fed an ethanol liquid diet or a control isocaloric diet for 5 weeks, and then subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Baicalin (200 mg/kg) was administered intraperitoneally 24 and 1 h before ischemia. After reperfusion, baicalin attenuated the increase in serum alanine aminotransferase activity. The levels of cytosolic cytochrome c protein expression, caspase-3 activity, the number of apoptotic cells increased after reperfusion, which were higher in ethanol-fed animals, were attenuated by baicalin. Following I/R, the hepatic lipid peroxidation was elevated, whereas hepatic glutathione content was decreased. These changes attenuated by baicalin. In ethanol-fed animals, baicalin augmented the increases in heme oxygenase-1 protein and mRNA expressions, and nuclear Nrf2 expression. In conclusion, our findings suggest that baicalin ameliorates I/R-induced hepatocellular damage by suppressing apoptosis and oxidative stress in alcoholic fatty liver.

• BMB Reports
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• v.42 no.12
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• pp.800-805
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• 2009

This study investigated the effect of subconjunctival injections of bevacizumab, an anti-VEGF antibody, on processes involved in corneal wound healing after alkali burn injury. Mice were divided into three groups: Group 1 was the saline-treated control, group 2 received subconjunctival injection of bevacizumab 1hr after injury and group 3 received bevacizumab 1 hr and 4 days after injury. Cornea neovascularization and opacity were observed using a slit lamp microscope. Corneal repair was assessed through histological analysis and immunostaining for CD31, $\alpha$-SMA, collagen I, and TGF-$\beta$2 7 days post-injury. In group 3, injection of bevacizumab significantly lowered neovascularization and improved corneal transparency. Immunostaining analysis demonstrated a reduction in CD31, $\alpha$-SMA and TGF-$\beta$2 levels in stroma compared to group 1. These results indicate that bevacizumab may be useful in reducing neovascularization and improving corneal transparency following corneal alkali burn injury by accelerating regeneration of the basement membrane.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.206-212
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• 2015

Background: Ginseng total saponin (GTS) contains various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The aim of this study was to study the effects of GTS on cardiac injury after global ischemia and reperfusion (I/R) in isolated guinea pig hearts. Methods: Animals were subjected to normothermic ischemia for 60 minutes, followed by 120 minutes of reperfusion. GTS significantly increased aortic flow, coronary flow, and cardiac output. Moreover, GTS significantly increased left ventricular systolic pressure and the maximal rate of contraction ($+dP/dt_{max}$) and relaxation ($-dP/dt_{max}$). In addition, GTS has been shown to ameliorate electrocardiographic changes such as the QRS complex, QT interval, and RR interval. Results: GTS significantly suppressed the biochemical parameters (i.e., lactate dehydrogenase, creatine kinase-MB fraction, and cardiac troponin I levels) and normalized the oxidative stress markers (i.e., malondialdehyde, glutathione, and nitrite). In addition, GTS also markedly inhibits the expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, and nuclear factor-${\kappa}B$, and improves the expression of IL-10 in cardiac tissue. Conclusion: These data indicate that GTS mitigates myocardial damage by modulating the biochemical and oxidative stress related to cardiac I/R injury.

• Archives of Pharmacal Research
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• v.27 no.1
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• pp.111-117
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• 2004

Hepatic microcirculatory failure is a major component of reperfusion injury in the liver. Recent data provided some evidence that endothelium-derived vasoconstrictors and vasodilators may be functionally important to the control of the total hepatic blood flow under these conditions of circulatory failure. Since Kupffer cells provide signals that regulate the hepatic response in ischemia/reperfusion (I/R), the aim of this study was to investigate the role of Kupffer cells in the I/R-induced imbalance of vasoregulatory gene expression. Rats were subjected to 60 min hepatic ischemia, followed by 5 h of reperfusion. The Kupffer cells were inactivated by gadolinium chloride ($GdCl_3$, 7.5 mg/kg body weight, intravenously) 1 day prior to ischemia. Liver samples were obtained 5 hrs after reperfusion for RT-PCR analysis of the mRNA for genes of interest: endothelin-1 (ET-1), its receptors $ET_A and ET_B$, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). ET-1 mRNA expression was increased by I/R. mRNA levels for $ET_A$ receptors showed no change, whereas $ET_B$ receptor transcripts increased in the I/R group. The increases in ET-1 and $ET_B$ mRNA were not prevented by the $GdCI_3$ pretreatment. The mRNA levels for iNOS and eNOS significantly increased within the I/R group with no significant difference between the I/R group and the $GdCl_3$-treated I/R group. HO-1 mRNA expression significantly increased in the I/R group and this increase was attenuated by $GdCI_3$. In conclusion, we have demonstrated that an imbalance in hepatic vasoregulatory gene expression occurs during I/R. Our findings suggest that the activation of Kupffer cells is not required for I/R-induced hepatic microvascular dysfunction.

• 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.

• Acute and Critical Care
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• v.33 no.4
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• pp.276-279
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• 2018

In pediatric patients, a laryngeal mask airway (LMA) is usually used during minor surgeries that require general anesthesia. No esophageal injury has been reported after insertion of an LMA. We report a case of an esophageal injury with intramural dissection after an $i-gel^{(R)}$ (size, 1.5; Intersurgical Ltd.) insertion in a pediatric patient. A 2-month-old male infant was hospitalized for left inguinal herniorrhaphy. After induction of anesthesia, a trained resident tried to insert an $i-gel^{(R)}$. However, it was only successful after three attempts. Dysphagia was sustained until postoperative day 10, and the pediatrician observed duplication of the esophagus on gastroendoscopy. However, a whitish mucosal lesion, which looked like a scar, was observed, and previous lesions suggestive of esophageal duplication were almost healed on postdischarge day 11. His condition was diagnosed as dysphagia and esophagitis due to an esophageal laceration, not esophageal duplication. He was scheduled for symptomatic treatment with a proton pump inhibitor. In conclusion, although an esophageal injury or perforation in pediatric patients is rare, an LMA insertion or a procedure such as aspiration or nasogastric tube insertion should be performed gently to avoid a possible injury to the esophagus in pediatric patients.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.940-945
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• 2002

The present study was done to determine the effect of trolox C, a hydrophilic analogue of vitamin E, on hepatic injury, especially the alteration in cytochrome P-450 (CYP)-dependent drug metabolism during ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Rats were treated intravenously with trolox C (2.5 mg/kg) or vehicle (PBS, pH 7.4), 5 min before reperfusion. Serum alanine aminotransferase and lipid peroxidation levels were markedly increased after I/R. This increase was significantly suppressed by trolox C. Cytochrome P-450 content was decreased after I/R but was restored by trolox C. There were no significant differences in ethoxyresorufin O-dealkylase (CYP 1A1) and methoxyresorufin O-dealkylase (CYP 1A2) activities among any of the experimental groups. Pentoxyresorufin O-dealkylase (CYP 2B1) activity was decreased and aniline p-hydroxylase (CYP 2E1) activity was increased after I/R. Both these changes were prevented by trolox C. Our findings suggest that trolox C reduces hepatocellular damage as indicated by abnormalities in microsomal drug-metabolizing function during I/R, and that this protection is, in part, caused by decreased lipid peroxidation.

• The Korean Journal of Pain
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• v.19 no.1
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• pp.33-44
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• 2006

Background: Peripheral nerve injury leads to neuropathic pain, including mechanical hyperalgesia (MH). Nerve discharges produced by an injury to the primary afferents cause the release of glutamate from both central and peripheral terminals. While the role of centrally released glutamate in MH has been well studied, relatively little is known about its peripheral role. This study was carried out to determine if the peripherally conducting nerve impulses and peripheral glutamate receptors contribute to the generation of neuropathic pain. Methods: Rats that had previously received a left L5 dorsal rhizotomy were subjected to a spinal nerve lesion (SNL) or brief electrical stimulation (ES, 4 Hz pulses for 5 min) of the left L5 spinal nerve. The paw withdrawal threshold (PWT) to von Frey filaments was measured. The effects of an intraplantar (i.pl.) injection of a glutamate receptor (GluR) antagonist or agonist on the changes in the SNL- or ES-produced PWT was investigated. Results: SNL produced MH, as evidenced by decrease in the PWT, which lasted for more than 42 days. ES also produced MH lasting for 7 days. MK-801 (NMDAR antagonist), DL-AP3 (group-I mGluR antagonist), and APDC (group-II mGluR agonist) delayed the onset of MH when an i.pl. injection was given before SNL. The same application blocked the onset of ES-induced MH. NBQX (AMPA receptor antagonist) had no effect on either the SNL- or ES-induced onset of MH. When drugs were given after SNL or ES, MK-801 reversed the MH, whereas NBQX, DL-AP3, and APDC had no effect. Conclusions: Peripherally conducting impulses play an important role in the generation of neuropathic pain, which is mediated by the peripheral glutamate receptors.