• 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 Nuclear Medicine
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• v.37 no.2
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• pp.83-93
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• 2003

Background: Lung-to-heart uptake ratio (LHR) in $^{201}Tl-chloride$ myocardial perfusion scan is believed to be a reliable marker for left ventricular (LV) dysfunction, but the clinical value of LHR is controversial for $^{99m}Tc-MIBI$ imaging. Furthermore, most of results suggesting lung uptake of $^{99m}Tc-MIBI$ as a potential marker for LV dysfunction used immediate post-stress images, instead of routine images acquired 1 hour after tracer injection. The goal of our study was to investigate whether LHR evaluated with routine gated $^{99m}Tc-MIBI$ imaging can reflect the degree of perfusion defect or left ventricular performance. Subjects and Methods: 241 patients underwent exercise $^{99m}Tc-MIBI$ myocardial SPECT were classified into normal myocardial perfusion (NP, n=135) and abnormal myocardial perfusion (AP, n=106) group according to the presence of perfusion defect. LHR was calculated from anterior projection image taken at 1-hour after injection. Two legions of interest (ROIs) were placed on left lung above LV and on myocardium showing the highest radioactivity. Subjects were classified by left ventricular ejection fraction (LVEF), as Gr-I: >50%, Gr-II: 36-50%, Gr-III: <36% and by summed stress score (SSS), as Gr-A: <4, Gr-B: 4-8, Gr-C: 9-13, Gr-D: >13, LHR was compared among these groups. Results: In NP group(n=135), LHR, were higher in men than women ($men:\;0.311{\pm}0.03,\;women:\;0.296{\pm}0.03,\;p<0.05$). Significant difference, in LHR were found between NP and AP groups both for men and women ($men:\;0.311{\pm}0.03\;vs\;.\;0.331{\pm}0.06,\;women:\;0.296{\pm}0.03\;vs.\;0.321{\pm}0.07.\;p<0.05$). There were weak negative correlation between LHR and LVEF (r=-0.342, p<0.05) and weak positive correlation between LHR and SSS (r=0.478, p<0.05) in men, but not in women (LVEF: r=-0.279, p=0.100, SSS: r=0.276, p=0.103). Increased LHR was defined when for more than mean + 2SD value ($men{\geq}0.38,\;women{\geq}0.37$) of the LHR of the subject with normal perfusion. Increased LHR were observed more frequently in subjects with lower LVEF (Gr-I: 11.1%, Gr-II: 27.0%, Gr-III: 35.4%, p<0.05) and higher SSS(Gr-A: 14.0%, Gr-B: 5.7%, Gr-C: 18.2%, Gr-D: 40.7%, p<0.05). Conclusions: LHRs obtained from routine $^{99m}Tc-MIBI$ gated SPECT images were weakly correlated with LVEF and perfusion defect. Although significant overlaps were observed between normal and abnormal perfusion group, LHRs could be used as an indirect marker of severe perfusion defect or reduced left ventricular function.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.4
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• pp.285-291
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• 2008

Purpose: Although automatic quantification software of myocardial perfusion SPECT provides highly objective and reproducible quantitative measurements, there is still some limitation in the direct use of quantitative measurements. In this study we derived parameters using normal variation of perfusion measurements, and tried to test the usefulness of these parameters. Materials and Methods: In order to calculate normal variation of perfusion measurements on myocardial perfusion SPECT, 55 patients (M:F = 28:27) of low-likelihood for coronary artery disease were enrolled and $^{201}TI$ rest/$^{99m}Tc$-MIBI stress SPECT studies were performed. Using 20-segment model, mean (m) and standard deviation (SD) of perfusion were calculated in each segment. As a myocardial viability assessment group, another 48 patients with known coronary artery disease, who underwent coronary artery bypass graft surgery (CABG) were enrolled. $^{201}TI$ rest/$^{99m}Tc$-MIBI stress / $^{201}TI$ 24-hr delayed SPECT was performed before CABG and SPECT was followed up 3 months after CABG. From the preoperative 24-hr delayed SPECT, $Q_{delay}$ (perfusion measurement), ${\Delta}_{delay}$ ($Q_{delay}$ - m) and $Z_{delay}$ (($Q_{delay}$ - m)/SD) were defined and diagnostic performances of them for myocardial viability were evaluated using area under curve (AUC) on receiver operating characteristic (ROC) curve analysis. Results: Segmental perfusion measurements showed considerable normal variations among segments. In men, the lowest segmental perfusion measurement was $51.8{\pm}6.5$ and the highest segmental perfusion was $87.0{\pm}5.9$, and they are $58.7{\pm}8.1$ and $87.3{\pm}6.0$, respectively in women. In the viability assessment $Q_{delay}$ showed AUC of 0.633, while those for ${\Delta}_{delay}$ and $Z_{delay}$ were 0.735 and 0.716, respectively. The AUCs of ${\Delta}_{delay}$ and $Z_{delay}$ were significantly higher than that of $Q_{delay}$ (p = 0.001 and 0.018, respectively). The diagnostic performance of ${\Delta}_{delay}$, which showed highest AUC, was 85% of sensitivity and 53% of specificity at the optimal cutoff of -24.7. Conclusion: On automatic quantification of myocardial perfusion SPECT, the normal variation of perfusion measurements were considerable among segments. In the viability assessment, the parameters considering normal variation showed better diagnostic performance than the direct perfusion measurement. This study suggests that consideration of normal variation is important in the analysis of measurements on quantitative myocardial perfusion SPECT.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.109-118
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• 1991

The present study was conducted to assess the possible contribution of arachidonic acid to generation of reactive oxygen metabolites and myocardial damage in ischemic-reperfused heart. Langendorff preparations of isolated rat heart were made ischemic by hypoperfusion (0.5 ml/min) for 45 min, and then followed by normal oxygenated reperfusion (7 ml/min). The generation of superoxide anion was estimated by measuring the SOD-inhibitable ferricytochrome C reduction. The myocardial cellular damage was observed by measuring LDH released into the coronary effluent. Oxygenated reperfusion following a period of ischemia produced superoxide anion, which was inhibited by both indomethacin (60 nmole/ml) and ibuprofen $(30\;{\mu}g/ml)$. Sodium arachidonate $(10^{-7}-10^{-2}{\mu}g/ml)$ administered during the period of oxygenated reperfusion stimulated superoxide anion production dose-dependently. The rate of arachidonate-induced superoxide generation was markedly inhibited by indomethacin, a cyclooxygenase inhibitor; nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, and by eicosatetraynoic acid (ETYA), a substrate inhibitor of arachidonic acid metabolism. The release of LDH was increased by Na arachidonate and was inhibited by superoxide dismutase. The release of LDH induced by arachidonic acid was also inhibited by indomethacin, NDGA and ETYA. In conclusion, the present result suggests that arachidonic acid metabolism is involved in the production of reactive oxygen metabolite and plays a contributory role in the genesis of reperfusion injuy of myocardium.

• Journal of radiological science and technology
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• v.32 no.4
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• pp.461-469
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• 2009

To predict the tumor grading, various imaging modalities have been applied clinically. This study determines clinical usefulness of perfusion MRI, using relative cerebral blood volume in grading of the gliomas. We did a retrospective review of 17 patients (mean age, 57.5 years; 11 male, 6 female) who underwent perfusion MR and conventional MRI, and then correlated pathologically after operation. Statistical analysis of regional cerebral blood volume and relative cerebral blood volume(rCBV) was performed by using softwares such as PAT by SIEMENS and Xmap ver 2.0 developed by ourselves. Six patients out of 13 were low-grade gliomas while eleven patients were the high-grade gliomas. Mean relative CBV (m_rCBV/white matter) in the low-grade gliomas was 1.62, and mean relative CBV(m_rCBV/cortex) was 0.12. In the high-grade gliomas, mean relative CBV(m_rCBV/white matter) and mean relative CBV(m_rCBV/cortex) were 33.53 and 0.96. Mean relative CBV of gliomas were elevated with a statistical difference(P<.05), compared with contralateral white matter(P=.019) or cortex(P=.025). Furthermore mean relative CBV(m_rCBV/white matter) was much higher than mean relative CBV(m_rCBV/cortex). Perfusion MRI using regional cerebral blood volume and rCBV is very useful imaging modality for grading the glioma.

• Journal of Chest Surgery
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• v.38 no.7 s.252
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• pp.489-495
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• 2005

In the surgical treatment of aortic dissection, aortic arch replacement under total circulatory arrest is often performed after careful inspection to determine the severity of disease progression. Under circulatory arrest, antegrade or retrograde cerebral perfusion is required for brain protection. Recently, antegrade cerebral perfusion has been used more, because of the limitation of retrograde cerebral perfusion. This study is to compare these two methods especially in the respect to neurological complications. Material and Method: Forty patients with aortic dissection involving aortic arch from May 2000 to May 2004 were enrolled in this study, and the methods of operation, clinical recovery, and neurological complications were retrospectively reviewed. Result: In the ACP (antegrade cerebral perfusion) group, axillary artery cannulation was performed in 10 out of 15 cases. In the RCP (retrograde cerebral perfusion) group, femoral artery Cannulation was performed in 24 out of 25 cases. The average esophageal and rectal temperature under total circulatory arrest was $17.2^{\circ}C\;and\;22.8^{\circ}C$ in the group A, and $16.0^{\circ}C\;and\;19.7^{\circ}C$ in the group B, respectively. Higher temperature in the ACP group may have brought the shorter operation and cardiopulmonary bypass time. However, the length of period for postoperative clinical recovery and admission duration did not show any statistically significant differences. Eleven out of the total 15 cases in the ACP group and thirteen out of the total 25 cases in the RCP group showed neurological complication but did not show statistically significant difference. In each group, there were 5 cases with permanent neurological complications. All 5 cases in the ACP group showed some improvements that enabled routine exercise. However all 5 cases in RCP group did not show significant improvements. Conclusion: The Antegrade, cerebral perfusion, which maintains orthordromic circulation, brings moderate degree of hypothermia and, therefore, shortens the operation time and cardiopulmonary bypass time. We concluded that Antegrade cerebral perfusion is safe and can be used widely under total circulatory arrest.

• Journal of Chest Surgery
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• v.30 no.10
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• pp.949-960
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• 1997

Background. Limited ischemic tolerance of the lung has remained one of the factors that limits the expansion of pulmonary transplantation as a treatment for end-stage pulmonary disease. Numerous studies on safe long term preservation for lung transplantation has been performed for the purpose of developing ideal preservation solution with extracellular type or intracellular type solutions. In this. study, we examined the efficacy of L DG solution in lung preservation longer than 20 hours by comparison with modified Euro-Collins solution. Iwethods. Thirty-(our adult mongrel dogs were divided into two groups. Donor lungs were flushed with LPDG solution(n=9) or modified Euro-Collins(MEC) solution(n=8) and stored for 24 hours at 1$0^{\circ}C$. All donor lungs were perfused through the pulmonary arteries with solutions containing prostaglandin El and verapamil. Left canine lung allotransplantations wereperformed. Assessment(hemodynamic indices and arterial blood gas analysis) of left implanted lung was made by occluding the right pulmonary artery for ten minutes using pulmonary artery Cuff. Assessment was repeated at the interval of 30 minutes, one hour, and two hours later after reperfusion and then chest X-ray, computed tomogram and lung perfusion scan were obtained. In survival dogs follow-up studies were done with assessment with chest X-ray, computed tomogram of the chest and lung perfusion scan on 7th day postoperatively. After preservation above 20 hours, pathological examinations for ultrastructural findings on right lung were performed in each group. Results. With respect to arterial oxygen tension, LPDG group was superior to MEC but there was no statistical significance for 2 hours after reperfusion. Mean pulmonary artery pressure was less increased(p < 0.05) and cardiac output higher(p <0.05) than MEC group until 2 hours after reperfusion. After 2 hours of reperfusion, both groups showed transplanted lung function deteriorated gradually. Perfusion scan of the transplanted lung in LPDG group showed better perfusion rate in immediate post-reperfusion, 3 days and 7 days later respectively but there was no statistical significance and corelation with PaO2 and computed tomoRravhic views. In scanning electron microscopy of pulmonary artery after preservation, LPDG group relatively shows less irregular protrusion of the inner surface of endothelial cell of poulmonary artery than MEC group. Conclusions, e concluded that LPDG solution can offer safe lung preservation above 20 hours with adequate immunosuppressive therapy and prevention of the infection.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.512-522
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• 1999

Background: Due to the paucity of suitable donor organs for lung allotransplantation, a number of techniques have been developed to improve the lung preservation. Ultrastructural studies of the morphologic changes of the flushing, preservation and reperfusion injury in donor lungs have rarely been reported. Methods: Adult dogs (n=46) were matched as donors and recipients for the single lung transplantation. The donor lungs were preserved after flushing with preservation solution and transplanted after 20-hours of preservation at $10^{\circ}C$. Ultrastructural features of the lung were examined after flushing, preservation and 2 hours after lung transplantation (reperfusion) respectively. Results: Electron microscopy after flushing showed focal alveolar collapse and mild swelling of type I epithelial cells. After preservation both type I epithelial cells and endothelial cells were swollen and destroyed focally. The endothelial cells showed protrusion of tactile-like structures into the lumina, blebs or vacuoles of the cytoplasm After reperfusion the lung tissue showed fibrin material in the alveoli, prominent type I epithelial cell swelling with fragmented cytoplasmic debris and marked endothelial cell swelling with vacuoles or tactile-like projections. The alveolar macrophages showed active phagocytosis. Scanning electron microscopic examination of the pulmonary parenchyma showed focally alveolar collapse and focal consolidation after the preservation and more prominent changes after the reperfusion procedure. The lungs preserved with low potassium dextran glucose solution, with additional prostaglandin $E_1(PGE_1)$ and verapamil(VP) showed relatively well preserved ultrastructures compared with those which were preserved with modified Euro-Collins or University of Wisconsin, and with additional $PGE_1$ and/or VP. Conclusion: The ultrastructural changes associated with flushing were mild in severity, the donor lungs were injured during the preservation, and further damage was occurred during the reperfusion. The reperfusion injury resulted in prominent pulmonary parenchymal alterations with a pattern of acute lung injury.

• Clinical and Experimental Pediatrics
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• v.45 no.5
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• pp.560-567
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• 2002

주산기 뇌손상은 주로 급격한 저산소-허혈 손상에 의하는데 급격한 산소 공급의 차단은 oxidative phosphorylation을 정지 시켜서 뇌대사를 위한 에너지 공급이 차단되게 된다. 에너지 공급이 차단된 뇌세포는 뇌세포막에서 세포 내외의 이온 농도 차를 유지시키던 ATP-dependent $Na^{+}-K^{+}$ pump의 기능이 정지 되고, 세포 내외의 농도 차에 따라 $Na^{+}$, $Cl^{+}$, $Ca^{{+}{+}}$의 대규모 세포 내로 이동이 일어난다. 세포 내로 calcium 이온의 이동은 glutamate 수용체의 활성화에 의해서도 일나는데, 세포 내 calcium 이온의 증가는 protease, lipase, nuclease 등을 활성화 시켜 세포를 사망에 이르게 하는 연속적이고 다양한 생화학적 반응을 일으키게 된다. Glutamate는 대표적인 신경 전달 물질인데 저산소-허혈 손상 시 glutamate 수용체의 지나친 흥분은 미성숙 뇌에 뇌손상을 유발하는데, NMDA 또는 non-NMDA 수용체와 복합체를 형성하고 있는 calcium 이동 통로를 활성화 시켜 세포 내 calcium 이온을 증가시키고, 그 외에 metabotropic recetor는 G-protein의 활성화 등을 통해 뇌손상을 유발하는 다양한 생화학적 반응을 매개한다. 저산소-허혈 손상 후 재산소화와 재관류가 일어나면서 뇌세포의 지연성 사망(secondary neuronal death)이 일어나는데 이는 초기 손상 후 뒤이어 일어나는 다양한 생화학적 반응에 의하는데 다량의 산소 자유기 발생, nitric oxide의 생성, 염증 반응과 싸이토카인, 신경전도 물질의 과흥분 등이 관여하며, 신경 세포 사망은 세포괴사(necrosis)뿐 아니라 일부는 세포 사멸(apoptosis)로 알려진 의도된 세포 사망(programmed cell death)에 의한 것으로 생각되고 있다(Fig. 2).

• Journal of Chest Surgery
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• v.37 no.2
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• pp.119-130
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• 2004

Decrease in cardiac function after open heart surgery is due to an ischemia induced myocardial damage during surgery, and ischemic preconditioning, a condition in which the myocardial damage does not accumulate after repeated episodes of ischemia but protects itself from damage after prolonged ischemia due to myocytes tolerating the ischemia, is known to diminish myocardial damage, which also helps the recovery of myocardium after reperfusion, and decreases incidences of arrythmia. Our study is performed to display the ischemic preconditioning and show the myocardial protective effect by applying cardioplegic solution to the heart removed from rat. Material and Method: Sprague-Dawley male rats were used, They were fixed on a modified isolated working heart model after cannulation. The reperfusion process was according to non-working and working heart methods and the working method was executed for 20 minutes in which the heart rate, aortic pressure, aortic flow and coronary flow were measured and recorded. The control group is the group which the extracted heart was fixed on the isolated working heart model, recovered by reperfusion 60 minutes after infusion and preserved in the cardioplegic solution 20 minutes after the working heart perfusion and aortic cross clamp, The thesis groups were divided into group I, which ischemic hearts that were hypoxia induced were perfused by cardioplegic solution and preserved for 60 minutes; group II, the cardioplegic solution was infused 45 seconds (II-1), 1 minutes (II-2), 3 minutes (II-3), after the ischemia induction, 20 minutes after working heart perfusion and aortic cross clamp; and group III, hearts were executed on working heart perfusion for 20 minutes and aortic cross clamp was performed for 45 seconds (III-1), 1minute (III-2), 3 minutes (III-3), reperfused for 2 minutes to recover the heart, and then aortic cross clamping was repeated for reperfusion, all the groups were compared based on hemodynamic performance after reperfusion of the heart after preservation for 60 minutes. Result: The recovery time until spontaneous heart beat was longer in groups I, II-3, III-2 and III-3 to control group (p<0.01). Group III-1 (p<0.05) had better results in terms of recovery in number of heart rates compared to control group, and recovered better compared to II-1 (p<0.05). The recovery of aortic blood pressure favored group III-1 (p<0.05) and had better outcomes compared with II-1 (p<0.01). Group III-1 also showed best results in terms of cardiac output (p<0.05) and group III-2 was better compared to II-2 (p<0.05). Group I (p<0.01) and II-3 (p<0.05) showed more cardiac edema than control group. Conclusion: When the effects of other organs are dismissed, protecting the heart by infusion of cardioplegic solution after enforcing ischemia for a short period of time before the onset of abnormal heart beats for preconditioning has a better recovery effect in the cardioplegic group with preconditioning compared to the cardioplegic solution itself. we believe that further study is needed to find a more effective method of preconditioning.