• Journal of Chest Surgery
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• v.36 no.11
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• pp.799-811
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• 2003

Background: The aim of this study is to define the cardioprotective effects (hemodynamic, cytochemical and ultrastructural of the newly developed Histidine-Tryptophan-Ketoglutarate (HTK) cardioplegia compared to DelNido cardioplegia. Material and Method: Seventy-nine isolated rat hearts were divided into three groups on the basis of techniques of cardioplegia infusion. Twenty-eight hearts (Group 1) were flushed with cold DelNido cardioplegia with every 40 minutes for 2 hours. Twenty-seven hearts (Group 2) were flushed with cold HTK cardioplegia for once during the 2 hours. Twenty-four hearts (Group 3) were flushed with cold HTK cardioplegia with every 40 minutes for 2 hours. Heart rate, left ventricular developed pressure (LVDP), changes of + dp/dt max, coronary flow, and rate-pressure product value were measured at pre-ischemic, post-reperfusion 15 minutes, 30 minutes, and 45 minutes for hemodynamic study. Aspartate aminotransferase (AST), lactate dehydrogenase (LD), creatine kinase (CK), CK-MB, troponin-I, myoglobin, and lactate were measured at pre-ischemic and post-reperfusion 45 minutes for cytochemical parameters. Mitochondrial scores were counted in 3 cases from each group for ultrastructural assessment. Result: In hemodynamic study, there were no significant differences among group 1, group 2, and group 3. However, the decrease values of heart rate in group 2 and 3 exhibited significantly lower values than in group 1. In cytochemical study, there were no significant differences among group 1, group 2, and group 3. However, the increase values of lactate in group 2 and 3 exhibited significantly lower values than in group 1. In ultrastructural assessment, the mean myocardial mitochondria scores in group 1, group 2, and group 3 were 2.14$\pm$0.10, 1.52$\pm$0.57, and 2.10$\pm$0.16. Conclusion: HTK solution provides adequate myocardial protection with some advantages over DelNido solution in isolated rat hearts.

• Journal of Chest Surgery
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• v.31 no.9
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• pp.837-844
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• 1998

Background: Adenosine is secreted by myocardial cells during myocardial ischemia or hypoxia. It has many beneficial effects on arrhythmias, myocardial ischemia, and reperfusion ischemia. Although many investigators have demonstrated that cardioplegia that includes adenosine shows protective effects in myocardial ischemia or reperfusion injury, reports of the optimal dose of adenosine in cardioplegic solutions vary. We reported the results of beneficial effects of single dosage(0.75 mg/Kg/min) adenosine by use of self-made Langendorff system. But it is uncertain that dosage was optimal. The objective of this study is to determine the optimal dose of adenosine in cardioplegic solutions. Material and Method: We used a self-made Langendorff system to evaluate the myocardial protective effect. Isolated rat hearts were subjected to 90 minutes of deep hypothermic arrest(15$^{\circ}C$) with modified St. Thomas' Hospital cardioplegia including adenosine. Myocardial adenosine levels were augmented during ischemia by providing exogenous adenosine in the cardioplegia. Three groups of hearts were studied: (1) group 1 (n=10) : adenosine - 0.5 mg/Kg/min, (2) group 2(n=10): adenosine -0.75 mg/Kg/min, (3) group 3 (n=10) : adenosine -1 mg/Kg/min. Result: Group 3 resulted in a significantly rapid arrest time of the heart beat(p<0.05) but significantly slow recovery time of the heart beat after reperfusion(p<0.05) compared to groups 1 and 2. Group 2 showed a better percentage of recovery(p<0.05) in systolic aortic pressure, aortic overflow volume, coronary flow volume, and cardiac output compared to groups 1 and 3. Group 1 showed a a better percentage of recovery(p<0.05) in the heart rate compared to the others. In biochemical study of drained reperfusates, CPK and lactic acid levels did not show significant differences in all of the groups. Conclusion: We concluded that group 2 [adenosine(0.75 mg/Kg/min) added to cardioplegia] has better recovery effects after reperfusion in myocardial ischemia and is the most appropriate dosage compared to group 1 and 3.

• 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.

• Journal of Chest Surgery
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• v.32 no.9
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• pp.773-780
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• 1999

Background: It has been demonstrated that brief periods of calcium depletion and repletion (calcium-free preconditioning, CP) have cardioprotective effects as seen in ischemic preconditioning(IP) which enhances the recovery of post-ischemic contractile dysfunction and reduces the incidence of reperfusion-induced arrhythmia or infarct size after a prolonged ischemia. In the present study, we tested this paradoxical phenomenon in isolated rabbit hearts. Material and Method: Hearts isolated from New Zealand white rabbits(1.5∼2.0 Kg body weight) were perfused with Tyrode solution using the Langendorff technique. After stabilizing the baseline hemodynamics, the hearts were subjected to 45 minutes of global ischemia followed by 120 minutes of reperfusion with IP(IP group, n=7) or without IP (ischemic control group, n=7). IP was induced by a single episode of 5 minutes global ischemia and 10 minutes reperfusion. In the CP group(n=7), the hearts were subjected to perfusion with Tyrode solution with calcium depletion for 5 minutes and repletion for 10 minutes, and 45 minutes of ischemia and 120 minutes of reperfusion. Left ventricular function including developed pressure, dP/dt, heart rate, left ventricular end-diastolic pressure and coronary flow was measured. Infarct size was determined by staining with 1% triphenyltetrazolium chloride and planimetry. Data were analyzed by a one-way analysis of variance and Tukey's post-hoc test. Result: In comparison with the ischemic control group, IP significantly enhanced the recovery of the left ventricular function including the left ventricular developed pressure, contractility, and coronary flow; in contrast, these functional parameters of the CP group tended to be lower than those of the ischemic control group. However, the infarct size was significantly reduced by IP or CP(p<0.05). Conclusion: These results suggest that in isolated Langendorff-perfused rabbit heart model, CP(induced by single episode of 5 minutes calcium depletion and 10 minutes repletion) could not improve the post-ischemic contractile dysfunction(after a 45-minute global ischemia) but it has an infarct size-limiting effect.

• Journal of Chest Surgery
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• v.40 no.1 s.270
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• pp.8-16
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• 2007

Background: We performed a prospective clinical study to evaluate the ultrastructural integrity of the myocardium after using Histidine-Tryptophan-Ketoglutarate (HTK) solution in comparison with blood cardioplegic solution during congenital heart surgery. Material and Method: Twenty two patients with acyanotic heart disease, who were scheduled for elective open heart surgery, were randomized into two groups. The HTK Group (n=11) received HTK cardioplegic solution; the blood group (n=11) received conventional blood cardioplegic solution during surgery. The preoperative diagnoses included ventricular septal defect (n=9) and atrial septal defect (n=2) in each group. A small biopsy specimen was taken from the right ventricle's myocardium, and this was processed for ultrastructural examination at the end of 30 minutes of reperfusion. Semiquantitative electron microscopy was carried out 'blindly' in 4 areas per specimen and in 5 test fields per area by 'random systematic sampling' and 'point and intersection counting'. The morphology of the mitochondrial membrane and cristae were then scored. The interstitial edema of the myocardium was also graded. Result: The semiquantitative score of the mitochondrial morphology was $19.65{\pm}4.75$ in the blood group and $25.25{\pm}5.85$ in the HTK group (p=0.03). 6 patients (54.5%) in the blood group and 3 patients (27.3%) in the HTK group were grade 3 or more for the interstitial edema of the myocardium. Conclusion: The ultrastructural integrity was preserved even better with HTK solution than with conventional blood cardioplegic solution.

• Journal of Chest Surgery
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• v.29 no.2
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• pp.199-207
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• 1996

Ischemic myocardial damage is inevitable to cardiac surgery. Myocardial damage after initiation of reperfusion through the coronary arteries is one of the most important determinants of a successful surgery. Adenosine is a potent vasodilator, and is also known to induce rapid cardioplegic arrest by its property of antagonizing cardiac calcium channels and activating the potassium channel. Thus, we initiated this study with adenosine to improve postischemic recovery in the isolated rat heart. We tested the hypothesis that adenosine could be more effective than potassium in inducing rapid cardiac arrest and enhancing postischemlc hemodynamic recovery. Isolated rat hearts, connected to the Langendorff appratus, were perfused with Krebs-Henseleit buffer and all hearts were subjected to arrest for 60 minutes. Three groups of hearts were studied according to the composition of cardioplegic solutions : Group A (n=10), adenosine 10mmo1/L+potassium free modified St. Thomas cardioplegia : Group B (n=10), adenosine 400mo1/L+S1. Thomas cardioplegia:Group C(control, n=10), St. Thomas cardioplegia. Adenosine-treated groups (group A & B) resulted in more rapid cardiac arrest than control group (C) (p< 0.01). There was greater improvement in recovery of coronary blood flow at 20 and 30 minutes of reperfusion in group A and at 20 minutes in group B when compared with control group(p<0.01). Recovery of systolic blood pressure at 10 minutes after reperfusion in group A and B was significantly superior to that in group C (p<0.01). Recovery of dp/dt at 10 minute after reperfusion in group A was also significantly superior to group C (p<0.05). Group A and B showed better recovery rates than control group in aortic blood flow, cardiac output, and heart rate, but there were no statistical differences. CPK levels of coronary flow in group A were significantly low (p< 0.01). We concluded that adenosine-enriched cardioplegic solutions have better effects on rapid cardiac arrest and postischemic recovery when compared with potassium cardioplegia.

• Journal of Chest Surgery
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• v.24 no.7
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• pp.669-673
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• 1991

Fructose-l, 6-diphosphate as an additive to cold crystalloid cardioplegia [St. Thomas sol.] was studied prospectively in 60 patients undergoing open heart surgery from January 1, 1991, to June 30, 1991. Thirty patients received cardioplegia with FDP[group I ] and 30 patients received cardioplegia without FDP [group II ]. There were no differences between two groups pre-operatively with regard to age, heart disease, cross-clamp time, cardiac enzymes, or hemodynamic measurements [p>0.05]. Cardiopulmonary bypass was established using ascending aorta and vena cava cannulation employing moderate systemic hypothermia [30oC nasopharyngeal temperature] and hemodilution All patients received cardioplegia through the aortic root at aortic root pressure of 80mm Hg. The composition of the cardioplegic solution and its delivery were identical in both groups except for the addition of FDP[1.5 mg/mL] in group I. The cardioplegic infusate consisted of St. Thomas Hospital solution. The initial dose was infused through the aortic root. Topical myocardial cooling with saline slush was employed in all patients. Recorded operative data were cardiopulmonary bypass and cross-clamp times, amount of cardioplegic infusate. Blood samples for assessment of lactate dehydrogenase [LDH], creatine kinase [CK] and transaminases [GOT, GPT] were obtained before and at 1,2,3,7th postoperative period. Better myocardial protection effect was noted in group I than group II with respect to the % change of cardiac enzymes, although the differences were not significant. We conclude that FDP is a safe additive to crystalloid cardioplegia and may be beneficial in open heart surgery patients.

• Journal of Chest Surgery
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• v.35 no.5
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• pp.387-391
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• 2002

Background: Postoperative morbidity and mortality in destroyed lung are relatively high. We tried to identify the prognostic factors affecting postoperative morbidity and mortality in destroyed lung through a retrospective study. Material and method: The retrospective study was undertaken in 112 patients who had undergone pneumonectomy or pleuropneumonectomy for destroyed lung at Severance Hospital from 1970 to 2000. We analyzed the correlation between postoperative morbidity and mortality and etiology, duration of disease, preoperative FEV1, presence or absence of peroperative empyema, operation timing, the side of operation, duration of operation, and operation type. Result: There were 55 men and 57 women, aged 20 to 81 years (mean 44 years). Etiologic diseases were tuberculosis in 86 patients(76.8%) including tuberculos empyema in 20 and tuberculous bronchiectasis in 4, pyogenic empyema in 12(10,7%), bronchiectasis in 12(10.7%), and lung abscess in 2(1.8%). Postoperative morbidity were 25%(n=28) and postoperative mortality was 6%(n=7). The presence of preoperative empyema(p=0.016), pleuropneumonectomy(p=0.037) and preoperative FEV1 of less than 1.75 L(P=0.048) significantly increased the postoperative morbidity, If operation time was less than 300min, postoperative morbidity(p=0.002) and mortality(p=0.03) were significantly low. Conclusion: Postoperative morbidity and mortality in destroyed lung were acceptable. Postoperative morbidity and mortality were significantly low when operation time was less than 300 min. Preoperative existence of empyema, pleuropneumonectomy and preoperative FEV1 of less than 1.75 L significantly increased postoperative morbidity.

• Journal of Chest Surgery
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• v.32 no.7
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• pp.603-612
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• 1999

Background : It has been documented that brief repetitive periods of ischemia and reperfusion (ischemic preconditioning, IP) enhances the recovery of post-ischemic contractile function and reduces infarct size after a longer period of ischemia. Many mechanisms have been proposed to explain this process. Recent studies have suggested that transient increase in the intracellular calcium may have triggered the activation of protein kinase C(PKC); however, there are still many controversies. Accordingly, the author performed the present study to test the hypothesis that preconditioning with high concentration of calcium before sustained subsequent ischemia(calcium preconditioning) mimics IP by PKC activation. Material and Method : The isolated hearts from the New Zealand White rabbits(1.5∼2.0 kg body weight) Method: The isolated hearts from the New Zealand White rabbits(1.5∼2.0 kg body weight) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to 45-minute global ischemia followed by a 120-minute reperfusion with IP(IP group, n=13) or without IP(ischemic control, n=10). IP was induced by single episode of 5-minute global ischemia and 10-minute reperfusion. In the Ca2+ preconditioned group, perfusate containing 10(n=10) or 20 mM(n=11) CaCl2 was perfused for 10 minutes after 5-minute ischemia followed by a 45-minute global ischemia and a 120-minute reperfusion. Baseline PKC was measured after 50-minute perfusion without any treatment(n=5). Left ventricular function including developed pressure(LVDP), dP/dt, heart rate, left ventricular end-diastolic pressure(LVEDP) and coronary flow(CF) was measured. Myo car ial cytosolic and membrane PKC activities were measured by 32P-${\gamma}$-ATP incorporation into PKC-specific pepetide. The infarct size was determined using the TTC (tetrazolium salt) staining and planimetry. Data were analyzed using one-way analysis of variance(ANOVA) variance(ANOVA) and Tukey's post-hoc test. Result: IP increased the functional recovery including LVDP, dP/dt and CF(p<0.05) and lowered the ascending range of LVEDP(p<0.05); it also reduced the infarct size from 38% to 20%(p<0.05). In both of the Ca2+ preconditioned group, functional recovery was not significantly different in comparison with the ischemic control, however, the infarct size was reduced to 19∼23%(p<0.05). In comparison with the baseline(7.31 0.31 nmol/g tissue), the activities of the cytosolic PKC tended to decrease in both the IP and Ca2+ preconditioned groups, particularly in the 10 mM Ca2+ preconditioned group(4.19 0.39 nmol/g tissue, p<0.01); the activity of membrane PKC was significantly increased in both IP and 10 mM Ca2+ preconditioned group (p<0.05; 1.84 0.21, 4.00 0.14, and 4.02 0.70 nmol/g tissue in the baseline, IP, and 10 mM Ca2+ preconditioned group, respectively). However, the activity of both PKC fractions were not significantly different between the baseline and the ischemic control. Conclusion: These results indicate that in isolated Langendorff-perfused rabbit heart model, calcium preconditioning with high concentration of calcium does not improve post-ischemic functional recovery. However, it does have an effect of limiting(reducing) the infart size by ischemic preconditioning, and this cardioprotective effect, at least in part, may have resulted from the activation of PKC by calcium which acts as a messenger(or trigger) to activate membrane PKC.

• Journal of Distribution Research
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• v.5 no.2
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• pp.49-68
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• 2001

In this chapter, we summarize the results on the optimal location selection and present limitation and direction of research. In order to reach the objective, this study selected and tested the interaction model which obtains the value of co-ordinates on location selection through the optimization technique. This study used the original variables in the model, but the results indicated that there is difference in reality. In order to overcome this difference, this study peformed market survey and found the new variables (first data such as price, quality and assortment of goods, and the second data such as aggregate area, and area of shop, and the number of cars in the parking lot). Then this study determined an optimal variable by empirical analysis which compares an actual value of market share in 1988 with the market share yielded in the model. However, this study found the market share in each variables does not reflect a reality due to an assumption of λ-value in the model. In order to improve this, this study performed a sensitivity analysis which adds the λ value from 1.0 to 2.9 marginally. The analyzed result indicated the highest significance with the market share ratio in 1998 at λ of 1.0. Applying the weighted value to a variable from each of the first data and second data yielded the results that more variables from the first data coincided with the realistic rank on sales. Although this study have some limits and improvements, if a marketer uses this extended model, more significant results will be produced.