• YAKHAK HOEJI
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• v.41 no.1
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• pp.117-125
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• 1997

The pharmacological effects of benzopyran potassium channel openers (lemakalim, KR-30450 and KR-30818) on the occlusion/reperfusion-induced myocardial infarction were investigat ed. In anesthetized rats, subjected to 45-min occlusion of the left anterior descending coronary artery (LAD) followed by 90-min reperfusion, the infarct size was measured by calculating the ratio of infarct zone to area at risk (IZ/AAR) with the Evans blue/TTC technique. Rats were intravenously given vehicle (1% DMSO), lemakalim, KR-30450, and KR-30818 alone or in combination with a selective K$_{ATP}$ blacker glibenclamide, 30 min prior to coronary occlusion. Compared to vehicle, lemakalim (30 ${\mu}$g/kg i.v.), the active enantiomer of cromakalim, had a tendancy to decrease infarct size. KR-30450(30 ${\mu}$g/kg, i.v.). the newly synthetized potassium channel openers (PCOs), caused a reduction of infarct size (from 70${\pm}$4%to 57${\pm}$5%). but KR-30818 (30 ${\mu}$g/kg, i.v.), a metabolite of KR-30450. did not modify infarct size. It seem ed likely that glibenclamide (0.3mg/kg, i.v.), given in combination, reduced the effects of these PCOs, especially KR-30450 (30 ${\mu}$g/kg, i.v.) on the infarct size. These results indicate that. in the coronary occluded rat model of ischemia, lemakalim and KR-30450 may exert cardioprotective activity through a reduction of infarct size, the effect being considered related to the opening of K$_{ATP}$ channel.

• The Korean Journal of Nuclear Medicine
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• v.25 no.1
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• pp.37-45
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• 1991

Infarct size is a major determinant of prognosis after acute myocardial infarction. Up to date, however, clinically available tests to estimate this size have not been sufficiently accurate. Twelve lead electrocardiogram and wall motion abnormality measurement are not quantitative, and creatine phophokinase (CPK) measurement is inaccurate in the presence of reperfusion or right ventricular infarction. Methods have been developed to localize and size acute myocardial infarcts with agents that are selectively sequestered in areas of myocardial damage, but previously used agents have lacked sufficient specificity. Antibodies that bind specifically only to damaged myocardial cells may resolve this problem and provide an accurate method for noninvasively measuring infarct size. We determined the accuracy with which infarcted myocardial mass can be measured using single photon emission computed tomography (SPECT) and radiolabeled antimyosin antibodies. Seven patients with acute myocardial infarction and one stable angina patient were injected with 2 mCi of Indium-111 labeled antimyosin antibodies. Planar image and SPECT was performed 24 hours later. None of the patients had history of prior infarcts, and none had undergone reperfusion techniques prior to the study, which was done within 4 days of the attack. Planar image showed all infarct patients to have postive uptakes in the cardiac region. The location of this uptake correlated to the infarct site as indicated by electrocardiography in most of the cases. The angina patient, however, showed no such abnormal uptake. Infarct size was determined from transverse slices of the SPECT image using a 45% threshold value obtained from a phantom study. Measured infarct size ranged from 40 to 192 gr. There was significant correlation between the infarct size measured by SPECT and that estimated from serial measurements of CPK (r=0.73, p<0.05). These date suggest that acute myocardial infarct size can be accurately measured from SPECT Indium-111 antimyosin imaging. This method may be especially valuable in situations where other methods are unreliable, such as early reperfusion technique, right ventricular infarct or presence of prior infarcts.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.435-440
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• 2010

Valproic acid (VPA) is a well-known anti-epileptic and mood stabilizing drug. A growing number of reports demonstrate that VPA is neuroprotective against various insults. Despite intensive efforts to develop new therapeutics for stroke over the past two decades, all treatments have thus far failed to show clinical effect because of treatment-limiting side effects of the drugs. Therefore, a safety-validated drug like VPA would be an attractive candidate if it has neuroprotective effects against ischemic insults. The present study was undertaken to examine whether pre- and post-insult treatments with VPA protect against brain infarct and neurological deficits in mouse transient (tMCAO) and permanent middle cerebral artery occlusion (pMCAO) models. In the tMCAO (2 hr MCAO and 22 hr reperfusion) model, intraperitoneal injection of VPA (300 mg/kg, Lp.) 30 min prior to MCAO significantly reduced the infarct size and the neurological deficit. VPA treatment immediately after reperfusion significantly reduced the infarct size. The administration of VPA at 4 hr after reperfusion failed to reduce the infarct size and the neurological deficit. In the pM CAO model, treatment with VPA (300 mg/kg, i.p.) 30 min prior to MCAO significantly attenuated the infarct size, but did not affect the neurological deficit. Western blot analysis of acetylated H3 and H4 protein levels in extracts from the ischemic cortical area showed that treatment with VPA increased the expression of acetylated H3 and H4 at 2 hrs after MCAO. These results demonstrated that treatment with VPA prior to ischemia attenuated ischemic brain damage in both mice tMCAO and pMCAO models and treatment with VPA immediately after reperfusion reduced the infarct area in the tMCAO model. VPA could therefore be evaluated for clinical use in stroke patients.

• Progress in Medical Physics
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• v.22 no.1
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• pp.42-51
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• 2011

Nuclear medicine images (SPECT, PET) were widely used tool for assessment of myocardial viability and perfusion. However it had difficult to define accurate myocardial infarct region. The purpose of this study was to investigate methodological approach for automatic measurement of rat myocardial infarct size using polar map with adaptive threshold. Rat myocardial infarction model was induced by ligation of the left circumflex artery. PET images were obtained after intravenous injection of 37 MBq $^{18}F$-FDG. After 60 min uptake, each animal was scanned for 20 min with ECG gating. PET data were reconstructed using ordered subset expectation maximization (OSEM) 2D. To automatically make the myocardial contour and generate polar map, we used QGS software (Cedars-Sinai Medical Center). The reference infarct size was defined by infarction area percentage of the total left myocardium using TTC staining. We used three threshold methods (predefined threshold, Otsu and Multi Gaussian mixture model; MGMM). Predefined threshold method was commonly used in other studies. We applied threshold value form 10% to 90% in step of 10%. Otsu algorithm calculated threshold with the maximum between class variance. MGMM method estimated the distribution of image intensity using multiple Gaussian mixture models (MGMM2, ${\cdots}$ MGMM5) and calculated adaptive threshold. The infarct size in polar map was calculated as the percentage of lower threshold area in polar map from the total polar map area. The measured infarct size using different threshold methods was evaluated by comparison with reference infarct size. The mean difference between with polar map defect size by predefined thresholds (20%, 30%, and 40%) and reference infarct size were $7.04{\pm}3.44%$, $3.87{\pm}2.09%$ and $2.15{\pm}2.07%$, respectively. Otsu verse reference infarct size was $3.56{\pm}4.16%$. MGMM methods verse reference infarct size was $2.29{\pm}1.94%$. The predefined threshold (30%) showed the smallest mean difference with reference infarct size. However, MGMM was more accurate than predefined threshold in under 10% reference infarct size case (MGMM: 0.006%, predefined threshold: 0.59%). In this study, we was to evaluate myocardial infarct size in polar map using multiple Gaussian mixture model. MGMM method was provide adaptive threshold in each subject and will be a useful for automatic measurement of infarct size.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.993-999
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• 2005

This research was peformed to investigate protective effect of Sophora Subprostrata fractions against focal ischemic brain damage after middle cerebral artery(MCA) occlusion using intraluminal suture. Rats were divided into six groups: MCA-occluded group(Control): each administered groups with Sophora Subprostrata total phase(Total), Sophora Subprostrata Aqueous phase (Aqueous), Sophora Subprostrata BuOH phase(BuOH), and Sophora Subprostrata Alkaloid phase(Alkaloid) after MCA-occlusion; sham-operated group(Sham). The right MCA was occluded by A poly-L-lysine coated 4-0 nylon suture thread through the internal carotid artery permanently. Sophora Subprostrata and fractions were administered orally(Smg/ml) for 7 days after MCA-occlusion. The Drain tissue was stained with $2\%$ triphenyl tetrazolium chloride on ischemic brain tissue(2mm section). The results showed that 1) Sophora Subprostrata total phase reduced infarct size and total infarct volume compared to the control group at 24 hours after MCA-occlusion, 2) Sophora Subprostrata Aqueous phase reduced infarct size and total infarct volume compared to the control group at 24 hours after MCA-occlusion, 3) Sophora Subprostrata Alkaloid phase reduced infarct size compared to the control group at 24 hours after MCA-occlusion, but 4) at 7 days after MCA-occlusion, Sophora Subprostrata did not show effective recovery compared with control group. Sophora Subprostrata has protective effects against brain damage at the early stage of focal cerebral ischemia. Sophora Subprostrata total and Aqueous phase produced more pronounced protective effect against focal ischemic brain damage.

• The Journal of Korean Medicine
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• v.25 no.1
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• pp.117-128
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• 2004

Objectives : This research was performed to investigate effect of Samul-tang-gamibang against focal cerebral ischemic damage after middle cerebral artery occlusion(MCAO). Methods : This research was used rats which were against focal cerebral ischemic damage by MCAO. It was used Zea Longa's theory and Belayev's methods to give rise to focal cerebral ischemic damage by MCAO. After 7days later, we drew out the brain and then had frozen and dyeing it and we had taken a picture to measure of the damaged area in each brain section. We determined the Neurological Index and tested the Foot-fault test and Roatated test to appraise the fall of motion ability result from cerebral ischemic damage. Results : The results of the experiment are as follows. 1. Samul-tang-gamibang reduced infarct size of sample group compared to control group at 7 day after MCAO. 2. Samul-tang-gamibang reduced infarct volume of sample group compared to control group at 7 day after MCAO. 3. Samul-tang-gamibang reduced foot-fault index of sample group compared to control group at 5,7 day after MCAO. Conclusions : Samul-tang-gamibang has protective effects against ischemic brain damage and had significant reduced infarct size and infarct volume of Rt-MCAO.

• Korean Journal of Radiology
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• v.2 no.1
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• pp.21-27
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• 2001

Objective: To identify and evaluate the lateral border zone by comparing the size and distribution of the abnormal signal area demonstrated by MR imaging with the infarct area revealed by pathological examination in a reperfused myocardial infarction cat model. Materials and Methods: In eight cats, the left anterior descending coronary artery was occluded for 90 minutes, and this was followed by 90 minutes of reperfusion. ECG-triggered breath-hold turbo spin-echo T2-weighted MR images were initially obtained along the short axis of the heart before the administration of contrast media. After the injection of Gadomer-17 and Gadophrin-2, contrast-enhanced T1-weighted MR images were obtained for three hours. The size of the abnormal signal area seen on each image was compared with that of the infarct area after TTC staining. To assess ultrastructural changes in the myocardium at the infarct area, lateral border zone and normal myocardium, electron microscopic examination was performed. Results: The high signal area seen on T2-weighted images and the enhanced area seen on Gadomer-17-enhanced T1WI were larger than the enhanced area on Gadophrin-2-enhanced T1WI and the infarct area revealed by TTC staining; the difference was expressed as a percentage of the size of the total left ventricle mass (T2= 39.2 %; Gadomer-17 =37.25 % vs Gadophrin-2 = 29.6 %; TTC staining = 28.2 %; p < 0.05). The ultrastructural changes seen at the lateral border zone were compatible with reversible myocardial damage. Conclusion: In a reperfused myocardial infarction cat model, the presence and size of the lateral border zone can be determined by means of Gadomer-17- and Gadophrin-2-enhanced MR imaging.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.3
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• pp.1-13
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• 2009

Objectives : This study evaluates neuroprotective effect of Gastrodiae Rhizoma on apoptosis in the cerebral infarct. Methods : Cerebral infarct was induced by the middle cerebral artery occlusion (MCAO) for 2 hours with intraluminal thread method in Sprague-Dawley rats. Then ethanol extract of Gastrodiae Rhizoma was administered orally for 3 days. Infarct area and volume were evaluated with TTC staining. Neuronal apoptosis was identified with TUNEL labeling. Apoptosis modulatory effect was observed with immunohistochemical Bax, Bcl-2, iNOS, and MMP-9 expressions in penumbra. Results : 1. Ethanol extract of Gastrodiae Rhizoma reduced infarct size partly and volume significantly of in the MCAO rat brain. 2. Ethanol extract of Gastrodiae Rhizoma reduced TUNEL positive cell ratio in the penumbra of MCAO rat brain significantly. 3. Ethanol extract of Gastrodiae Rhizoma suppressed Bax, iNOS and MMP-9 expression in the penumbra of MCAO rat brain significantly. 4. Ethanol extract of Gastrodiae Rhizoma did not change Bcl-2 expression in the penumbra of MCAO rat brain. But expression ratio of Bcl-2 against Bax was increased in the Gastrodiae Rhizoma group. Conclusions : These results suggest that Gastrodiae Rhizoma plays an anti-apoptotic neuroprotective effect through suppression of Bax, iNOS, and MMP-9 expressions and relative up-regulation of Bcl-2 in the ischemic brain tissue.

• The Korea Journal of Herbology
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• v.29 no.3
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• pp.71-78
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• 2014

Objectives : This study evaluates the neuroprotective effects of Sopung-tang, a mixture of Notopterygii Rhizoma, Saposhnikoviae Radix, Angelicae Gigantis Radix, Cnidii Rhizoma, Hoelen, Aurantii Nobilis Pericarpium, Pinelliae Tuber, Linderae Radix, Angelicae Dahuricae Radix, Cyperi Rhizoma, Cinnamomi Ramulus, Asari Radix, Glycyrrhizae Radix on the cerebral infarct combined with hyperlipidemia. Method : The hyperlipidemia was induced by the beef tallow 30% diet for 14 days on Sprague-Dawley rats. The cerebral infarct was induced by the middle cerebral artery occlusion (MCAO) for 2 hours with intraluminal thread method. Then the water extract of Sopung-tang was administered a day for 5 days at 3 hours after the cerebral infarct by MCAO. Effect of Sopung-tang was evaluated with the infarct volume and edema percentage by a TTC-stained brain section, and the expressions of Bax and Bcl-2 in the brain tissue by a immunohistochemical stain method. Results : Sopung-tang reduced the infarct size partly in a TTC-stained brain section of the hyperlipidemic MCAO rats. Sopung-tang reduced the infarct volume of the hyperlipidemic MCAO rats significantly. Sopung-tang reduced the edema percentage of the hyperlipidemic MCAO rats, but not significant statistically. Sopung-tang suppressed the Bax expressions in the cerebral penumbra and caudate putamen of the hyperlipidemic MCAO rats significantly. Sopung-tang upregulated the Bcl-2 expression in the caudate putamen of the hyperlipidemic MCAO rats. Conclusion : These results suggest that Sopung-tang plays an anti-apoptotic neuroprotective effect through the suppression of Bax and up-regulation of Bacl-2 expressions in the brain tissues.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.5
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• pp.893-898
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• 2002

Citri Reticulatae Viride Pericarpium extract(CRVP) have been used in oriental medicine for many centuries as a therapeutic agent for smoothing the liver and regulating the circulation of qi, and promoting digestion and removing stagnated food. The effects of CRVP on the inhibition of brain damage in cerebral ischemia is not known. Therefore, this Study was designed to investigate the cerebral protective effects of CRVP on the transient cerebral ischemia using modern techniques, and further to provide the possibility of scientification of oriental medicine. The size of cerebral infarct size was measured by morphometry, and brain edema was measured by morphometry and brain water content determination. The results were a$ follows ; 1. Water fraction of CRVP was reduced infect area of rats brain slices which were subjected to a transient cerebral ischemia in a dose-dependent manner. 2. Methylene chloride fraction and hexane fraction of CRVP was significantly reduced infarct area of rats brain slices which were subjected to a transient cerebral ischemia in a dose-dependent manner. 3. Methylene chloride fraction and hexane fraction of CRVP was significantly reduced infarct volume of rats brain which was subjected to a transient cerebral ischemia in a dose-dependent manner. 4. Methylene Chloride fraction and hexane fraction of CRVP was significantly decreased brain edema induced by a transient cerebral ischemia in a dose-dependent manner. 5. Methylene chloride fraction and hexane fraction of CRVP was significantly decreased brain water content of rats which were subjected to a transient cerebral ischemia. It is suggested that CRVP has an anti-ischemic effect through the inhibition of brain damage in a transient cerebral ischemia, and that in future further development of main effective constituent in CRVP can provide a novel therapeutic strategy for cerebral ischemia.