• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.82-82
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• 1993

허혈-재관류손상 심근세포의 DNA에서 8-hydroxydeoxyguanosine (8-OHdG) 생성을 검토하였다. 흰쥐 적출심장의 Langendorff 관류 표본에서 대동맥 차단에 의한 60분 허혈후 산소가 포화된 Kredb-Henseleit용액으로 30분간 재관류 하므로서 허혈-재관류 손상을 유도하였다. 재관류 후 심근세포에서 DNA를 추출하고 HPLC(EC detector)를 이용하여 8-OHdG를 측정하였다. 실험결과 허혈-재관류 심근세포의 DNA에서 8-OHdG 함량이 증가하였으며 이는 $O_2$ 제거물질인 superoxide dismutase와 OH 제거물질인 mannitol에 의하여 방지되었다. Xanthine oxidase외 경쟁적 길항약인 allopurinol도 8-OHdG 생성을 억제하였으며 단백분해효소 억제제인 phenylsulfonylfluoride 그리고 관류액에서 칼슘의 제거 또한 허혈-재관류 심근 DNA의 생성을 방지하였다. 이상의 결과 허혈심근의 재관류시 8-OHdG 생성이 증가하며 이는 재관류 손상과 같은 산화성 심근손상을 평가하는 좋은 Index가 될 수 있을 것으로 여겨진다.

• Journal of the korean veterinary medical association
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• v.45 no.6
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• pp.539-543
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• 2009

심근 손상은 창상 환자에서 심장 기능에 뚜렷한 영향을 미칠 수 있지만 심각한 창상에 가려져 종종 간과됩니다. 심하지 않은 심근손상에 의한 부정맥은 스스로 치유되기도 하지만 저혈압, 쇠약, 순환부전과 같은 증상을 일으키는 부정맥은 조기에 인지하여 치료하지 않을 경우 생명을 위협할 수 있음을 잊어서는 안 될 것 같습니다.

• Journal of Chest Surgery
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• v.31 no.1
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• pp.20-27
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• 1998

It is well known that troponin T(below TnT) is present in the myocardial cells and released during myocardial damage, so it`s very specific enzyme to myocardium. Availability of cardiac specific TnT in assessing perioperatively myocardial damage was evaluated from 34 open heart surgery patients. They consisted of 11 ischemic heart, 13 acquired valvular heart and 10 congenital heart cases. Patients were divided into two groups, group A(patients with myocardial damage) and group B(patients without myocardial damage), according to the symptom of chest pain suspecting angina and the ECG findings of ST segment and T wave changes which show myocardial ischemia and injury. Serum TnT levels were measured by enzyme immunoassay method preoperatively, immediately postoperatively, postoperative day 1, day 2, day 3, and day 7. We observed and analyzed the changes of serum TnT levels in two groups and compared the serum TnT levels with CK-MB levels measured at the same time. In group A, serum TnT levels showed 1.37$\pm$0.26$\mu$g/L, 3.16$\pm$0.66$\mu$g/L, 2.39$\pm$0.74$\mu$g/L, 2.49$\pm$0.76$\mu$g/L, and 1.23$\pm$0.60$\mu$g/L, immediate postoperatively, postoperatively day1, day2, day3, and day7, respectively. It was observed there were significant differences compared with those of group B(0.38$\pm$0.04$\mu$g/L, 0.34$\pm$0.05$\mu$g/L, 0.25$\pm$0.03$\mu$g/L, 0.24$\pm$0.04$\mu$g/L, and 0.11$\pm$0.03$\mu$g/L) during identical periods(P<0.01). Serum CK-MB level in group A significantly elevated to 145.04$\pm$35.08 IU/L on the postoperative day 1 compared to group B(31.28$\pm$5.87 IU/L, P<0.05), However, it stiffly decreased from day 2 and returned to preoperative level at day 3. When serum TnT level more than 1.0$\mu$g/L is thought to reflect myocardial damage, serum TnT had 100% of sensitivity and 87% of specificity in diagnosing the postoperative myocardial damage(p<0.01). I conclusion, serum TnT levels increased significantly at very early stage of myocardial damage and persisted much longer period than CK-MB. This suggests that serum TnT has more advantage and availability in assessing the perioperatively myocardial damage than any other tests.

• Journal of Chest Surgery
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• v.29 no.8
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• pp.850-860
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• 1996

Oxygen free radicals and their metabolites have been implicated as possible causes of reperrusion injury In animal models. Their role in the clinical setting is still controversial. The aim of this study was to evaluate the degree of tissue damage, oxidative stress. and changes in the antioxidant enzyme system in patients undergoing cor nary artery bypass graft operations(CABG) with myocardial protection by cold blood cardioplegia. In patients undergoing CABG(n:10). the levels of lactate dehydrogenate(LDH), creatine phosphokinase MB fraction(CK-MB), and malondialdehyde(M DA) were measured In the coronary sinus effluent before aortic cross clamping and 20 minutes after reperfusion. At the same time, the myocardial tissue activities of superoxide dismutase(SOD). catalase(CAT), glutathione peroxiddse(GSHPX), glutathione reductase (GSSGRd), and glucose 6-phosphate dehydrogenate(GfPDH ) were determined in the right atrial auricle excised before aortic cross clamping and in the left atrial auricle excised 20 minutes after reperfuslon. The levels of increased significantly after reperrusion(p< U.05). There were no significant changes in CAT and CfPDH levels. Western blot analysis was performed to study the induction of antioxidant enzyme and demonstrated increased amount of Cu,Zn-SOD.

• Journal of Chest Surgery
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• v.34 no.3
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• pp.203-211
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• 2001

배경: AT$_1$수용체의 길항제가 세포 수준에서 심근을 재관류 손사으로부터 보호할수 있다는 것으로 알려져 있지만, 생체내에서의 효과나 그 기전은 아직 명확히 밝혀지지 않았다. 본 연구에서는 백서 심근 허혈 모델을 이용하여, AT$_1$ 수용체의 길항제들 중 하나인 irbesartan이 심근이 재관휴 손상에 미치는 효과를 알아보고, 재관류 손상을 매개하는 한 각지 기전으로서 세포자멸의 기여에 대하여 연구하고자 하였다. 대상 및 방법: Sprague-Dawley 백서에서 무작용 부형약(10% gum arabic: 1군, 개체수=14관) irbesartan(50mg/kg/day :II 군, 개체수=12)을 각각 3일 동안 24시간마다 경구로 투여하였다. 실험동물의 좌 관상 동맥을 45분간 결찰하였다가, 그 후 2시간 동안 재관류시킨 다음 심장을 적출 하였다. TTC(triphenyltetrazolium chloride) 염색법을 이용하여, 허혈 노출 부위에 대한 심근 경색 부위의 비율을 측정하였다. Agarose gel 전기영동상의 DNa 분절 양상과 TUNEL(TdT-mediated dUCP nick end labeling) 염색을 관찰하여 세포자멸이 일어난 정도를 평가하였다. 세포자멸을 조절하는데 관여하는 것으로 알려진 Bcl-2(B-cell lymphoma 2 gene), Bad 등의 단백과 ERK (extracellular signal-regulated kinase), p-38 등 신호전달체계에 작용하는 MAPKs(mitogen-activated protein kinases)의 발현을 측정하기 위하여 Western blot을 시행하였다. 결과: 허혈 노출부위에 대한 심근 경색부위의 비율은 II군(42$\pm$2.7%)이 I군( 64.1$\pm$4.65)에 비해 유의하게 작았다.(p< 0.05), Agarose gel 전기영동상의 DNA laddering 양상은 I군에서 보다 높게 발현되었다. Bad와 ERK2의 발현은 두 군간에 유의한 차이가 없었다. 결론: AT$_1$수용체 길항제인 irbesartan은 생체에서 심근의 재관류 손상을 줄이는 효과가 있었다. 이 효과는 적어도 부분적으로 나만 심근세포의 세포자멸이 감소한 것에 기인한 것으로 설명할 수 있으며, 이 항-세포 자멸 효과는 Bcl-2의 발현증가와 관련이 있는 것으로 추정되었다.

• Journal of Chest Surgery
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• v.31 no.6
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• pp.567-575
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• 1998

Panax Ginseng C.A. Meyer has been known for hundreds of years as the most valuable drug having mysterious effects among all the herbal medicines and plants in Korea. Also, many experimental studies have been performed recently that the various effects were identified and applied clinically. So we attempted an experimental study on the effect of ginsenoside Rg1 mixtures in an isolated rat heart with the use of the Langendorff model. The objective of this study was to determine whether this ginsenoside Rg1 mixtures would protect the myocardial injury after ischemic arrest and reperfusion. Isolated rat hearts were allowed to equilibrate for 20 minutes and were then subjected to 15 minutes of normothermic ischemia. After this ischemic period, isolated rat hearts were allowed to reperfusion for 10 minutes(Ischemic Group). In other group , isolated rat hearts were perfused for 60 minutes continuously with normothermia( Normothermic Group). Hemodynamic and biochemical parameters such as heart rate, left ventricular pressure, +dp/dt max, coronary blood flow and cardiac enzymes were measured during initial perfusion, ischemia, reperfusion period (Ischemic group) and 20, 40 and 60 minutes after continuous perfusion(Normothermic group). After completion of the experiment, this data was evaluated and the following results were obtained. 1. Heart rates showed an increase in both ischemic and normothermic experimental groups, but statistically significant differences were not identified. 2. LVP(Left Ventricular Pressure) showed statistically significant differences in both ischemic and normothermic experimental groups(p<0.005, p<0.01). 3. +dp/dt max showed statistically significant differences in both ischemic and normothermic experimental groups(p<0.01, p<0.01). 4. There were no statistically significant differences in coronary blood flow and cardiac cenzymes in all groups, but experimental groups seemed to have better protection and recovery. These results suggest that ginsenoside Rg1 mixtures has a protective effect on the myocardial injury after ischemia and reperfusion.

• Proceedings of the KTCVS Conference
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• 1995.10a
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• pp.1-1
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• 1995

• Applied Microscopy
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• v.19 no.1
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• pp.1-18
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• 1989

It has been debated whether postischemic reperfusion is necessarily beneficial to salvage the myocardium after ischemic insult or not. Therefore, this study was undertaken to compare the ultrastructural changes as well as the distribution of $Ca^{2+}$ in the ventricular myocardial cells after transient ischemia and after postischemic reperfusion, and to suspect to what extent the postischemic reperfusion is beneficial. After 10 minutes of ischemia, the heart developed wide I bands, glycogen depletion, intramyofibrillar edema, mitochondrial swelling, clumping and migration of chromatin, ghosts of lipid droplets, disintegration of cell junctions, sarcolemmal disruption, and loss of $Ca^{2+}$ binding capacity of the sarcolemma and the mitochondria. In spite of reperfusion, in a large number of cells, the ultrastructure was more severely damaged, however, $Ca^{2+}$ binding capacity of the sarcolemma and the mitochondria restored. These results suggest that postischemic reperfusion may help the myocardial cells to restore their function to control $Ca^{2+}$ to a certain extent, but that it could aggravate the ischemic insult.

• Journal of Sasang Constitutional Medicine
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• v.13 no.1
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• pp.70-78
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• 2001

ADR유발성 심근독성에 대한 심근세포의 손상기전을 규명하기 위해 ADR의 독성을 MTT정량, NR정량, LDH활성도 및 심박동을 측정하였다. 배양된 심근세포에서 청심연자탕 전탕액의 심근세포 보호효과는 LDH활성도 측정과 심박동 측정을 통해 관찰할 수 있었다. 이 실험을 통해 다음과 같은 결과를 얻을 수 있었다. 1. ADR은 배양심근세포에서 세포의 생존능력을 떨어뜨렸고, LDH의 활성도를 높였으며, 심박동수를 감소시켰다. 2. 청심연자탕 전탕액은 배양심근세포에서 ADR에 의해 증가된 LDH 활성도를 유의하게 감소시켰다. 3. 청심연자탕 전탕액은 배양심근세포에서 ADR에 의해 감소된 심박동을 유의하게 증가시켰다. 이상의 결과를 통해 ADR은 신생 마우스에서 적출해낸 배양 심근세포에서 독성효과를 나타냈음을 알 수 있었으며, 청심연자탕 전탕액은 ADR에 의해 유발된 심근세포독성에 매우 효과적으로 방어효과를 나타냄을 알 수 있었다.

• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.53-61
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• 1988

The effect of antioxidants on the myocardial cellular damage which occurs during reoxygenation of hypoxic myocardium was examined in isolated rat hearts. The roles of oxygen free radical and lipid peroxidation in reoxygenation injury of myocardium were also investigated. In Langenorff preparation of isolated rat heart, which was made hypoxic by perfusion with the substrate free, hypoxic cardioplegic solution ($37^{\circ}C$, 90 min), the release of cytosolic enzymes (creatine phosphokinase, lactic dehydrogenase) and a lipid peroxidation product, malondialdehyde into the coronary effluent were abruptly increased by reoxygenation. The release of enzymes was closely parallel to that of MDA. These increases of enzymes and lipid peroxidation product were suppressed to various degrees in the presence of scavengers of superoxide anion (superoxide dismutase, 10,000 U), hydrogen peroxide (catalase, 25,000 U) and hydroxyl radical (dimethyl sulfoxide, 10%). A natural antioxidant, ${\alpha}-tocopherol$(4.5 uM) and a synthetic one, butylated hydroxytoluene (2 uM) suppressed the release of cytosolic enzymes with the concomittent reduction of lipid peroxidation as measured by malondialdehyde release into the coronary effluent. These effects of antioxidants were dose dependent, and were more pronounced when the antioxidants were administered throughout hypoxic and reoxygenation periods than given during reoxygenation period only. These results suggest that cytotoxic oxygen free radicals produced in the myocardium during reoxygenation may be responsible fur the myocardial cellular injury by enhancing the lipid peroxidation of cellular membranes. Furthermore, the antioxidants may exert protective effect against reoxygenation damage of hypoxic myocardium through the inhibition of lipid peroxidation reaction.