• The Korean Journal of Physiology and Pharmacology
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• 제4권4호
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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.

• Journal of Chest Surgery
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• 제49권4호
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• pp.232-241
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• 2016

Background: Paraplegia is a devastating complication following operations on the thoracoabdominal aorta. We investigated whether histidine-tryptophan-ketoglutarate (HTK) solution could reduce the extent of ischemia/reperfusion (IR) spinal cord injuries in a rat model using a direct delivery method. Methods: Twenty-four Sprague-Dawley male rats were randomly divided into four groups. The sham group (n=6) underwent a sham operation, the IR group (n=6) underwent only an aortic occlusion, the saline infusion group (saline group, n=6) underwent an aortic occlusion and direct infusion of cold saline into the occluded aortic segment, and the HTK infusion group (HTK group, n=6) underwent an aortic occlusion and direct infusion of cold HTK solution into the occluded aortic segment. An IR spinal cord injury was induced by transabdominal clamping of the aorta distally to the left renal artery and proximally to the aortic bifurcation for 60 minutes. A neurological evaluation of locomotor function was performed using the modified Tarlov score after 48 hours of reperfusion. The spinal cord was harvested for histopathological and immunohistochemical examinations. Results: The spinal cord IR model using direct drug delivery in rats was highly reproducible. The Tarlov score was 4.0 in the sham group, $1.17{\pm}0.75$ in the IR group, $1.33{\pm}1.03$ in the saline group, and $2.67{\pm}0.81$ in the HTK group (p=0.04). The histopathological analysis of the HTK group showed reduced neuronal cell death. Conclusion: Direct infusion of cold HTK solution into the occluded aortic segment may reduce the extent of spinal cord injuries in an IR model in rats.

• 한국임상수의학회:학술대회논문집
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• 한국임상수의학회 2007년도 추계국제학술대회 및 컨퍼런스
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• pp.630-630
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• 2007

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.192.2-193
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• 2001

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.421.2-421.2
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• 2002

Recent studies show that KR-31378 ［(2S.3SAR)-N"-cyano-N-(6-amino-3A-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2H-benzopyran-4-yl)-N${\cdots}$-benzylguanidine］ has the neuroprotective effect as evidenced by the limitation of the size of infarct of the ischemia-reperfusion injury after an administration of KR-31378. In the literature. however. kinetics of KR-31378 distribution into the brain has not been systematically studied. (omitted)

• BMB Reports
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• 제53권11호
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• pp.582-587
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• 2020

It is well known that oxidative stress participates in neuronal cell death caused production of reactive oxygen species (ROS). The increased ROS is a major contributor to the development of ischemic injury. Indoleamine 2,3-dioxygenase 1 (IDO-1) is involved in the kynurenine pathway in tryptophan metabolism and plays a role as an anti-oxidant. However, whether IDO-1 would inhibit hippocampal cell death is poorly known. Therefore, we explored the effects of cell permeable Tat-IDO-1 protein against oxidative stress-induced HT-22 cells and in a cerebral ischemia/reperfusion injury model. Transduced Tat-IDO-1 reduced cell death, ROS production, and DNA fragmentation and inhibited mitogen-activated protein kinases (MAPKs) activation in H₂O₂ exposed HT-22 cells. In the cerebral ischemia/reperfusion injury model, Tat-IDO-1 transduced into the brain and passing by means of the blood-brain barrier (BBB) significantly prevented hippocampal neuronal cell death. These results suggest that Tat-IDO-1 may present an alternative strategy to improve from the ischemic injury.

• Journal of Chest Surgery
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• 제29권6호
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• pp.593-598
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• 1996

과거에 심근보호에 대한 많은 조사는 저온의 고칼릅 심정지액 및 국소적 냉각에 의한 방법으로는한 계가 있다는 지적이 있었다. 따라서 최근의 실험들은 재관류의 방법에 따른 허혈 후 심근회복에 대하여 촛점이 맞춰 지고 있다. 재관류 시 산소에 의한 심근손상이 밝혀 짐으로써 oxygen free radical scavenger에 대한 관심이 높아지고 있다. 따라서 본 교실에서는 쥐에게 항산화제로서 비타민 C를 먹인 후 Langendorf'r system을 이용하여 허혈 및 재관류 시 좌심실 기능의 변화를 관찰하였다 대상은 체중 190-))Og의 Sprague-Dawley쥐를 암수 구별없이 사용하였다. 편의상 비타민을 먹이지 않 은 대조군을 Group A (n=10)라 하였고 200mg의 비타민을 먹인 실험군을 Group R (n=10)라 하였다. 실 험군의 경우는 비타민 C 200mg을 경구투여한 후 24시간에 시행하였다. 방법은 언저 복강을 통해 헤파 린과 펜토탈을 주입한 후 심장을 적출하여 Langendorff system에 거치하고 비운동성 역관류를 시켰다. 관류액은 변형된 Krebs-Henseleit solution을 사용하였다. 좌심실내에 풍선을 삽입하여 polygraph를 통해 좌심실의 혈역학적 기능을 관찰하였다. 먼저 20분간 심 揚\ulcorner안정될 때까지 기다린 다음 51. Thomas심 정 지액으로 심정 지를 시킨후 30분간 허 혈시키고 다시 20분간 재관류시켰다. 각 Group에서 허혈전후의 좌심실압의 비, dp/dt의 비,박동수의 비, 재관류 후 첫 박동 및 안정될 때 까지의 시간을Group간에 비 교하였다. 좌심실압의 비는 Group A가 평균 88.9%, Group B가 114%로 실험군이 의의있게 높았으며 역시 dp/dt도 Group A가 89.6%, Group B가 1)2.9%로 실험군이 의의 있게 높았다 그러나 박동수의 비, 재관류 후 첫 박동 및 안정될 때 까지의 시간의 비교는 통계 학적 의의가 없었다. 결론적으로 항산화제로서 비타민 C는 허혈 및 재관류 시 좌심실 기능회복에 도움이 되었다. 그러나 향후 임상적 적용을 위해서는 더욱 자세하고 많은 실험 이 요구된다.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.531-538
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• 2015

Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusionevoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-$1{\beta}$ in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-${\kappa}B$, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of $I{\kappa}B$. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.

• The Korean Journal of Physiology and Pharmacology
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• 제26권1호
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• pp.47-57
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• 2022

Stiripentol is an anti-epileptic drug for the treating of refractory status epilepticus. It has been reported that stiripentol can attenuate seizure severity and reduce seizure-induced neuronal damage in animal models of epilepsy. The objective of the present study was to investigate effects of post-treatment with stiripentol on cognitive deficit and neuronal damage in the cornu ammonis 1 (CA1) region of the hippocampus proper following transient ischemia in the forebrain of gerbils. To evaluate ischemia-induced cognitive impairments, passive avoidance test and 8-arm radial maze test were performed. It was found that post-treatment with stiripentol at 20 mg/kg, but not 10 or 15 mg/kg, reduced ischemia-induced memory impairment. Transient ischemia-induced neuronal death in the CA1 region was also significantly attenuated only by 20 mg/kg stiripentol treatment after transient ischemia. In addition, 20 mg/kg stiripentol treatment significantly decreased ischemia-induced astrocyte damage and immunoglobulin G leakage. In brief, stiripentol treatment after transient ischemia ameliorated transient ischemia-induced cognitive impairment in gerbils, showing that pyramidal neurons were protected and astrocyte damage and blood brain barrier leakage were significantly attenuated in the hippocampus. Results of this study suggest stiripentol can be developed as a candidate of therapeutic drug for ischemic stroke.

• Journal of Chest Surgery
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• 제32권11호
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• pp.971-977
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• 1999

Background: Immunologic and inflammatory responses of cardiopulmonary bypass(CPB) influence postoperative mortality and morbidity with multiple organ injury. It has been reported that ischemia/reperfusion induced-myocardial injury during CPB is causative of release of inflammatory cytokines such as interleukin-6(IL-6) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$). The purpose of this study was to detect the time course of the activated cytokine and troponin-T(TnT), and to examine the correlation between such parameters during CPB. Material and Method: The serial samples were collected from arterial blood via radial arterial catheter in 23 patients who are underwent open heart surgery (OHS) with CPB, the IL-6, TNF-$\alpha$ and TnT were checked. Result: \circled1 IL-6, TNF$\alpha$- and TnT concentration increased significantly during CPB with a peaking level of CPB-off (p 0.05). \circled2 IL-6 had highly positive correlation with aortic cross clamping time and total bypass time(r=0.80, 0.78; p 0.05, respectively). \circled3 There was no correlation among IL-6, TNF-$\alpha$ and TnT. Conclusion: In conclusion, these data showed that elevated production of serum IL-6 during CPB was attributable to ischemia/reperfusion induced-myocardial damage. IL-6 will become a new and sensitive biological marker in assessment of myocardial damage during OHS with CPB. However, further studies will be needed to apply IL-6 in more patient population.