• 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 Chest Surgery
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• v.31 no.10
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• pp.924-927
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• 1998

Background: Myocardial cell death after myocardial infarction or reperfusion is classified into necrosis and apoptosis. Bcl-2 protein is a cytoplasmic protein, which inhibits apoptosis and is expressed in acute stage of myocardial infarction but not in normal heart. This study was performed to investigate whether Bcl-2 protein was expressed respectively to the reperfusion time. Materials and methods: Thirty nine New Zealand white rabbits weighing 1.5-4.8 kg (mean, 2.9kg) were alloted into 7 groups (n=5 in each group) which underwent left anterior descending coronary artery(LAD) occlusion for 30 minutes, followed by reperfusion. The animals were sacrificed at 1, 4, 8, 12, 24 hours, and 3, 7 days after occlusion. Ventricle was excised immediately after intervention. Tissues were fixed in 10% buffured formalin and embedded in paraffin. Bcl-2 protein was detected by immunohistochemical stain with using monoclonal antibody against Bcl-2 protein. Results: The positive immunohistochemical reactivity for Bcl-2 protein was observed in 12, 24 hours, and 3 days reperfusion groups. Bcl-2 protein was detected in salvaged myocytes surrounding the infarcted area. Conclusions: Bcl-2 protein is expressed at the late acute stage of infarct. Therefore, the expression of Bcl-2 protein may not protect acute cell death, but may play a role in the prevention of late cell death after myocardial is chemia-reperfusion.

• Journal of Chest Surgery
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• v.31 no.8
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• pp.739-748
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• 1998

Background: It has been well documented that transient occlusion of the coronary artery causes myocardial ischemia and finally cell death when ischemia is sustained for more than 20 minutes. Extensive studies have revealed that ischemic myocardium cannot recover without reperfusion by adequate restoration of blood flow, however, reperfusion can cause long-lasting cardiac dysfunction and aggravation of structural damage. The author therefore attempted to examine the effect of postischemic reperfusion on myocardial ultrastructure and to determine the rationales for recanalization therapy to salvage ischemic myocardium. Materials and methods: Young Holstein-Friesian cows(130∼140 Kg body weight; n=40) of both sexes, maintained with nutritionally balanced diet and under constant conditions, were used. The left anterior descending coronary artery(LAD) was occluded by ligation with 4-0 silk snare for 20 minutes and recanalized by release of the ligation under continuous intravenous drip anesthesia with sodium pentobarbital(0.15 mg/Kg/min). Drill biopsies of the risk area (antero-lateral wall) were performed at just on reperfusion(5 minutes), 1-, 2-, 3-, 6-, 12-hours after recanalization, and at 1-hour assist(only with mechanical respiration and fluid replacement) after 12-hour recanalization. The materials were subdivided into subepicardial and subendocardial tissues. Tissue samples were examined with a transmission electron microscope (Philips EM 300) at the accelerating voltage of 60 KeV. Results: After a 20-minute ligation of the LAD, myocytes showed slight to moderate degree of ultrastructural changes including subsarcolemmal bleb formation, loss of nuclear matrix, clumping of chromatin and margination, mitochondrial destruction, and contracture of sarcomeres. However, microvascular structures were relatively well preserved. After 1-hour reperfusion, nuclear and mitochondrial matrices reappeared and intravascular plugging by polymorphonuclear leukocytes or platelets was observed. However, nucleoli and intramitochondrial granules reappeared within 3 hours of reperfusion and a large number of myocytes were recovered progressively within 6 hours of reperfusion. Recovery was apparent in the subepicardial myocytes and there were no distinct changes in the ultrastructure except narrowed lumen of the microvessels in the later period of reperfusion. Conclusions: It is likely that the ischemic myocardium could not be salvaged without adequate restoration of coronary flow and that the microvasculature is more resistant to reversible period of ischemia than subendocardium and subepicardium. Therefore, thrombolysis and/or angioplasty may be a rational method of therapy for coronarogenic myocardial ischemia. However, it may take a relatively longer period of time to recover from ischemic insult and reperfusion injury should be considered.

• Journal of Chest Surgery
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• v.30 no.11
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• pp.1083-1091
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• 1997

This study was purposed to assess the result of coronary artery bypass graft surgery by analyzing and comparing the pre and postoperative myocardial perfusion state quantitatively by using myocardial SPECT. Twenty patients who received coronary artery bypass graft surgery since 1993 underwent both preoperative and postoperative myocardial SPECT and the result were analyzed. The mean age was 56.4$\pm$9.0 years, and the patients were composed of thirteen males and seven females. For quantitative analysis, we used polar maps of SPECT generated by Cedars-Sin i Medical Center program and we calculated perfusion scores, ischemic myocardial area ratios and reperfusion scores from polar maps. Preoperative mean stressfrest perfusion score was 7.3$\pm$ 1.117.7$\pm$ 1.0 and postoperative score was 8.1 $\pm$ 1 118.3$\pm$ 1.1. Preoperative mean stress ischemic myocardial area ratio was 0.32$\pm$0.2 and postoperative ratio was 0.15 $\pm$0.1. Postoperative mean perfusion score was significantly increased but, on the other hand, mean ischemic myocardial area ratio was significantly decreased as compared with preoperative values(p<0.01). Preoperative mean perfusion score of patients with postoperative roper(usion score more than 1.5 was significantly higher(p<0.01) than that of patients with postoperative reperfusion score less than 1.5. Preoperative perfusion scores of coronary artery territories that had fixed perfusion defect at myocardial SPECT were significantly low(4.3 $\pm$0.514.6$\pm$0.6, stresslrest), nevertheless it proved quantitatively that there was improvement in myocardial perfusion after surgery by showing improved perfusion scores postoperatively. In conclusion, myocardial SPECT is useful method for quantitative analysis of the myocardial perfusion state after coronary artery bypass grafting surgery.

• 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.29 no.10
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• pp.1076-1080
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• 1996

The results about the myocardial protection of recta of the nitric oxide precursor L-arginine upon reperrusion injury after ischemia are diverse. These diversities may be model dependent. Experiments were designed and performed to investigate myocardial protection effects according to the concentration of L-arginine. The Isolated rat hearts were subjected in a 30 minutes oi normothermic ischemia and reperfused for 30 minutes with reperfusate containing 0, 1, 2, 3, 4 moil L-arginine. After 30 minutes of reperfusion, group with 1 and 2 mM/L L-arginine showed a trend of better recovery in left ventricular systolic function(left ventricular developed pressure, positive maximum dpfdt), diastolic function(negative maximum dpfdt) and coronary flow compared to control group(reperfusate no L-arginine). Recovery was impaired with a higher concentration, and at 4 moil L-arginine r covery was worse than control(p (0, 05). These results suggest that optimal concentration of L-arginine Is Important or the recovery of myocardial and endothelial function after ischemia and reperfusion.

• The Korean Journal of Nuclear Medicine
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• v.32 no.3
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• pp.259-265
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• 1998

Purpose: We studied early rest/24 hour delay T1-201 perfusion SPECT for prediction of wall motion improvement after reperfusion in patients with acute myocardial infarction. Materials and Methods: Among 17 patients (male/female= 11/6, age: $59{\pm}13$) with acute myocardial infarction, 15 patients were treated with percutaneous transcoronary angioplasty (direct:2, delay: 11) and intravenous urokinase (2). Spontaneous resolution occurred in infarct-related arteries of 2 patients. We confirmed TIMI 3 flow of infarct-related artery after reperfusion in all patients with coronary angiography. We performed rest T1-201 perfusion SPECT less then 6 hours after reperfusion and delay T1-201 perfusion SPECT next day. T1-201 uptake was visually graded as 4 point score from normal (0) to severe defect (3). Rest T1-201 uptake ${\le}2$ or combination of rest T1-201 uptake ${\le}2$ or late reversibility were considered to be viable. Myocardial wall motion was graded as 5 point score from normal (1) to dyskinesia (5). Myocardial wall motion was considered to be improved when a segment showed an improvement ${\ge} 1$ grade in follow up echo compared with the baseline values. Results: Among 98 segments with wall motion abnormality, the severity of myocardial wall motion decrease was as follow: mild hypokinesia: 18/98 (18%), severe hypokinesia: 28/98 (29%), akinesia: 51/98 (52%), dyskinesia: 1/98 (1%). The wall motion improved in 85%. Redistribution (13%), and reverse redistribution (4%) were observed in 24 hour delay SPECT. Positive predictive value (PPV) and negative predictive value (NPV) of combination of late reversibility and rest T1-201 uptake were 99%, and 54%. PPV and NPV of rest T1-201 uptake were 100% and 52% respectively. Predictive values of combination of rest T1-201 uptake and late reversibility were not significantly different compared with predictive values of rest T1-201 uptake only. Conclusion: We conclude that early T1-201 perfusion SPECT predict myocardial wall motion improvement with excellent positive but relatively low negative predictive values in patients with acute myocardial infarction after reperfusion.

• Journal of Chest Surgery
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• v.31 no.2
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• pp.95-101
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• 1998

Ischemic preconditioning is known to have protective effect on myocardial function at prolonged ischemic insult but the mechanism of the effect is not clearly known. The effect of the preconditioning on the global ischemia using cardioplegic solution is not well known. To evaluate the effect of global myocardial preconditioning on the functional recovery after cardioplegic arrest and two hours of hypothermic storage, we used the isolated rat heart and two hours cardioplegic arrest time at $0^{\circ}C$. In the experimental group(n=10), after baseline functional data was obtained, ischemic preconditioning was induced with 1 min of global normothermic ischemia for three times before the arrest period. In the control group(n=10), hearts underwent no ischemic precondi- tioning. After 2 hrs of cardioplegic arrest and storage in the $0^{\circ}C$ cardioplegic solution reperfusion was done and hemodynamic data were collected at post-reperfusion 20 min. Heart with ischemic preconditioning showed improved functional recovery at post reperfusion 20 min in peak developed pressure and dP/dT. In percent change of the peak pressure, preconditioning group showed 93.20$\pm$15.7% recovery rate compared to baseline data, and control group showed 67.3$\pm$15.6% recovery rate. In percent change of the dP/dT, control group showed 54.7$\pm$18.2% recovery rate and preconditioning group showed 78.1$\pm$15.1% recovery rate. Percent changes in heart rate and coronary flow showed no significant difference between two groups and there was no significant differences in amount of cardioplegic delivery between groups. Our data suggest ischemic preconditioning may have protective effect on recovery state after cardioplegic arrest and 2 hr ischemic storage of isolated rat heart and its mechanism is not related to the amount of the cardioplegic delivery amount.

• The Korean Journal of Nuclear Medicine
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• v.34 no.1
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• pp.30-38
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• 2000

Purpose: We investigated the role of myocardial perfusion SPECT in prediction of ventricular dilatation and the role of revascularization including thrombolytic therapy and PTCA in prevention of ventricular dilatation after an acute myocardial infarction (AMI). Materials and Methods: We performed dipyridamole stress, 4 hour redistribution, and 24 hour reinjection Tl-201 SPECT in 16 patients with AMI two to nine days after attack. Perfusion and wall motion abnormalities were quantified by perfusion index (PI) and wall motion index (WMI). Left ventricular ejection fraction (LVEF), WMI and ventricular volume were measured within 1 week of AMI and after average of 6 months. According to serial changes of left ventricular end-diastolic volume (LVEDV), patients were divided into two groups. We compared WMI, PI and LVEF between the two groups. Relationships among degree of volume, stress-rest PI, WMI, CKMB, Q wave, LVEF and revascularization were analysed using multivariate analysis. Results: Only initial rest perfusion index was significantly different between the two groups (p<0.05). While initial LVEF, stress PI, CKMB, trial of revascularization procedure, presence of Q wave and WMI were not significantly different between the two groups. Eight of 16 patients (50%) showed LV dilatation on follow-up echocardiography. Three of 3 patients (100%) who did not undergo revascualrization procedure documented LV dilatation. And only 5 (38%) of the remaining 13 patients who underwent revascularization revealed LV dilatation. There was no difference in infarct location between the two groups. By multivariate linear regression analysis in patients only undergoing revascularization, rest perfusion index was the only significant factor. Conclusion: Myocardial perfusion SPECT performed prior to revascularization was useful in prediction of LV dilatation after an AMI. Rest perfusion index on myocardial perfusion plays as a significant predictor of left ventricular dilatation after AMI. And revascularization appears to be a valuable procedure in alleviating LV dilatation after AMI with or without viable myocardium in a limited number of patients studied retrospectively.

• Journal of Chest Surgery
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• v.36 no.4
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• pp.242-254
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• 2003

Most of the studies conducted have investigated the beneficial effects of ischemic preconditioning on normothermic myocardial ischemia. However, the effect of preconditioning could be attenuated through the use of multidose cold cardioplegia as practiced in contemporary clinical heart surgical procedures. The purpose of this study was to investigate whether preconditioning improves postischemic cardiac function in a model of 25℃ moderate hypothermic ischemic heart induced by cold cardioplegia in isolated rat hearts. Material and Method: The isolated Sprague-Dawley rat hearts were randomly assigned to four groups. All hearts were perfused at 37℃ for 20 minutes with Krebs-Henseleit solution before the baseline hemodynamic data were obtained. Group 1 consisted of preconditioned hearts that received 3 minutes of global ischemic preconditioning at 37℃, followed by 5 minutes of reperfusion before 120 minutes of cardioplegic arrest (n=6). Cold (4℃) St. Thomas Hospital cardioplegia solution was infused to induce cardioplegic arrest. Maintaining the heart at 25℃, infusion of the cardioplegia solution was repeated every 20 minutes throughout the 120 minutes of ischemic period. Group 2 consisted of control hearts that underwent no manipulations between the periods of equilibrium and 120 minutes of cardioplegic arrest (n=6). After 2 hours of cardioplegic arrest, Krebs solution was infused and hemodynamic data were obtained for 30 minutes (group 1, 2: cold cardioplegia group). Group 3 received two episodes of ischemic preconditioning before 30 min of 37℃ normothermic ischemia and 30 minutes of reperfusion (n=6). Group 4 served as ischemic controls for group 3 (group 3, 4: warm ischemia group). Result: Preconditioning did not influence parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), rate-pressure product (RPP) and left ventricular dp/dt (LV dp/dt) in the cold cardioplegia group. (p=NS) However, preconditioning before warm ischemia attenuated the ischemia induced cardiac dysfunction, improving the LVSP, LVEDP, RPP, and LVdp/dt. Less leakage of CPK and LDH were observed in the ischemic preconditioning group compared to the control group (p<0.05). Conclusion: Ischemic preconditioning improved postischemic cardiac function after warm ischemia, but did not protect cold cardioplegic hearts.