• Toxicological Research
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• v.35 no.4
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• pp.343-351
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• 2019

Many in vitro developmental toxicity assays have been proposed over several decades. Since the late 1980s, we have made intermittent attempts to introduce in vitro assays as screening tests for developmental toxicity of inhouse candidate products. Two cell-based assays which were developed two decades apart were intensively studied. One was an assay of inhibitory effects on mouse ascites tumor cell attachment to a concanavalin A-coated plastic sheet surface (MOT assay), which we studied in the early days of assay development. The other was an assay of inhibitory effects on the differentiation of mouse embryonic stem cell to beating heart cells (EST assay), which we assessed more recently. We evaluated the suitability of the assays for screening in-house candidates. The concordance rates with in vivo developmental toxicity were at the 60% level. The EST assay classified chemicals that inhibited cell proliferation as embryo-toxic. Both assays had a significant false positive rate. The assays were generally considered unsuitable for screening the developmental toxicity of our candidate compounds. Recent test systems adopt advanced technologies. Despite such evolution of materials and methods, the concordance rates of the EST and MOT systems were similar. This may suggest that the fundamental predictivity of in vitro developmental toxicity assays has remained basically unchanged for decades. To improve their predictivity, in vitro developmental toxicity assays should be strictly based on elucidated pathogenetic mechanisms of developmental toxicity.

• Journal of Chest Surgery
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• v.39 no.8 s.265
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• pp.604-610
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• 2006

Background: Recent improvements in interventional procedure and medical therapy for congestive heart failure result in an increase of number of patients with ischemic cardiomyopathy considered for coronary artery bypass grafting. We retrospectively review the results of CABG in these patients with decreased LV function to know the early and mid-term follow-up results. Material and Method: Between January 2001 and June 2005, 1,143 patients underwent coronary artery bypass grafting and 144 of these patients had preoperative left ventricular function of equal to or less than 35% ${(LVEF{\leq}\;35%)}$. There were off-pump coronary artery bypass grafting (OPCAB) in 66 cases (45.8%), on-pump beating heart coronary artery bypass grafting in 34 cases (23.6%) and conventional coronary artery bypass grafting in 44 cases (30.6%). The combined operations including mitral annuloplasty were 48 cases in thirty five patients (24.3%). Result: The mean number of dstal anastomosis were $3.5{\pm}1.3$. The median postoperative duration of stay in intensive care unit and hospital was 2 days and 8 days, respectively. There were 6 early death (4.2%) and causes of deaths were ventricular tachycardia in 5 patients, small bowel infarction in one patient. Mean follow-up time was $21{\pm}14$ months $(4{\sim}54\;months)$. The 1-year was $95{\pm}2%$ and 3-year survival rate was $83{\pm}7%$, the 1-year and 3-year cardiac event-free survival were ${88{\pm}3%\;and\;69{\pm}7%}$, respectively. Conclusion: Based on satisfactory early and mid-term results in our study, CABG should be carried out as actively as possible in patients with ischemic cardiomyopathy. Postoperative aggressive management for ventricular arrhythmia would be helpful for better results.

• Journal of Chest Surgery
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• v.36 no.5
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• pp.329-334
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• 2003

Backgound: Cryoablation and radiofrequency ablation have been used to treat the atrial fibrillation. Some reports insisted that the microwave ablation Is a better method for a deep and extensive lesion. Material and Method: From December 2001 to July 2002, we peformed 8 microwave ablations in patients who needed mitral valve surgery (7 MVR, 1 MVR+AVR). There were 3 men and 5 women, and their mean age was 43.4$\pm$8.3 years and mean follow up period was 5.6$\pm$2.4 months respectively. The microwave was applied on endocardium or epicardium by Lynx (Afx, inc.) using a power of 45 watts for 25 seconds. We studied the left atrial dimension, the left atrial function and the sinus conversion with echocardiography and electro-cardiography at three times; 1) before the operation, 2) immediately after the operation, and 3) 6 months after the operation. Result: There was no complication and no mortality. The mean aortic clamping time was 104.6$\pm$25.0 minutes, and the mean total bypass time was 130.5$\pm$28.7 minutes. The rate of sinus conversion was 75%, A wave across the mitral valve was a mean of 77.0$\pm$24.8 cm/sec, and the AVE was a mean of 0.46$\pm$0.17 at 5.6 months postoperatively Conclusion: There was no difference in the early result of microwave ablation compared to other methods. The microwave ablation was an acceptable method due to its convenient application especially in beating heart.

• Journal of Chest Surgery
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• v.41 no.6
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• pp.710-717
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• 2008

Background: Atrial fibrillation is associated with several complications such as cerebro-vascular accidents and peripheral arterial embolism. Most of the patients who have this arrhythmia chronically feel their heart beating and so they are frightened; therefore, the quality of a patient's life is decreased. The purpose of this article is to determine the long term results of a modified Maze procedure and the factors that influence the success of the procedure. Material and Method: This study enrolled 88 patients who underwent the modified Maze with using cryoablation between June, 2001 and February, 2007. The 88 consecutive patients were divided into two groups ac cording to how the pulmonary veins were isolated, that is, with or without cryoablation. There were 58 patients who were isolated by cutting and sewing in the right pulmonary veins and by cyroablation in the left pulmonary veins in group 1 (group 1, n=58), and 30 patients who underwent isolation by cryoablation in the right & left pulmonary veins were placed in group 2 (group 2, n=30). The ECG was checked at discharge to determine the sinus conversion rate and we followed up the patients to determine whether or not the patients maintained sinus rhythm. We also checked the ECG at the last visit to determine the patients' heart rhythm. Result: The mean follow up time was $44.3{\pm}19.2$ months. At discharge, 72.4% of the patients in group 1 were in proper sinus rhythm and 66.7% of the patients in group 2 were in proper sinus rhythm. At the last follow up, 81% of the patients in group 1 were in normal sinus rhythm and 60% of the patients in group 2 were in normal sinus rhythm. When we analyzed the data via the Kaplan-Meier method, 86.5% of the patients were free from atrial fibrillation (% free from AF) at 1 year, 80% of the patients were free from atrial fibrillation at 5 year in group 1 and 70% of the patients were free from atrial fibrillation at 1 year and 51 % of the patients in group 2 were free from atrial fibrillation at 5 year. Conclusion: The modified Maze technique using cryoablation was a simple and effective procedure. But the success rate of the Maze technique using cryoblation is lower than that of the standard Maze III. The method using cryoablation shorten the operation time, but we must conduct more studies to get a better result of the modified Maze technique with using cryoablation.

• Journal of Chest Surgery
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• v.37 no.2
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• pp.131-138
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• 2004

High-flow gas insufflation to get a bloodless field during off-pump coronary artery bypass may have adverse effects on the coronary endothelium. This study was designed (1) to elucidate the effect of carbon dioxide gas insufflations on the coronary endothelium at different flow rates and (2) to assess the protective effect of humidifcation against the coronary endothelial damage. Material and Method: In nine pigs, the left anterior descending coronary artery (LAD) was exposed after a median sternotomy. The LAD was divided into 4 segments and a coronary arteriotomy was made in each LAD segment in the beating heart. The far distal arteriotomy was exposed to room air for 10 minutes and was harvested as a control. Non-humidified carbon dioxide gas at a continuous flow rate of 5 L/min (Group I), humidified carbon dioxide gas at a continuous flow rate of 5 L/min (Group II), and humidified carbon dioxide gas at a continuous flow rate of 10 L/min (Group III) were insufflated for 10 minutes on each coronary arteriotomy site, respectively. After harvesting the coronary segments, hematoxylin-eosin staining, elastic fiber staining, and immunostaining with a CD34 monoclonal antibody were performed to evaluate the depth of endothelial damage and to count the residual endothelial cells, Result: In all three groups (Group I, II, and III), internal elastic laminae were preserved, however, the endothelial layers were significantly damaged by carbon dioxide gas insufflation. The mean percentages of remaining endothelial cells were 20,9$\pm$16.7%, 39.3$\pm$19.6%, and 6.8$\pm$5.3%, in groups I, II, and III, respectively. The percentages of remaining cells were significantly higher in group II than in groups I and III (p=0.008). The percentages of remaining cells were significantly higher in group I than in group III (p=0.008). Conclusions: The harmful effect of carbon dioxide gas insufflation on the coronary endothelium was dependent on the flow rate. The addition of humidification did not protect the coronary endothelium from denudation injury caused by high flow carbon dioxide gas insufflations.

• Journal of Chest Surgery
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• v.39 no.5 s.262
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• pp.354-358
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• 2006

Background: Pulsatile pumps for extracorporeal circulation have been known to be better for tissue perfusion than non-pulsatile pumps but be detrimental to blood corpuscles. This study is intended to examine the risks and benefits of $T-PLS^{TM}$ through the comparison of clinical effects of $T-PLS^{TM}$ (pulsatile pump) and $Bio-pump^{TM}$ (non-pulsatile pump) used for coronary bypass surgery. Material and Method: The comparison was made on 40 patients who had coronary bypass using $T-PLS^{TM}\;and\;Bio-pump^{TM}$ (20 patients for each) from April 2003 to June 2005. All of the surgeries were operated on pump beating coronary artery bypass graft using cardiopulmonary extra-corporeal circulation. Risk factors before surgery and the condition during surgery and the results were compared. Result: There was no significant difference in age, gender ratio, and risk factors before surgery such as history of diabetes, hypertension, smoking, obstructive pulmonary disease, coronary infarction, and renal failure between the two groups. Surgery duration, hours of heart-lung machine operation, used shunt and grafted coronary branch were little different between the two groups. The two groups had a similar level of systolic arterial pressure, diastolic arterial pressure and mean arterial pressure, but pulse pressure was measured higher in the group with $T-PLS^{TM}\;(46{\pm}15\;mmHg\;in\;T-PLS^{TM}\;vs\;35{\pm}13\;mmHg\;in\;Bio-pump^{TM},\;p<0.05)$. The $T-PLS^{TM}$-operated patients tended to produce more urine volume during surgery, but the difference was not statistically significant $(9.7{\pm}3.9\;cc/min\;in\;T-PLS^{TM}\;vs\;8.9{\pm}3.6\;cc/min\;in\;Bio-pump^{TM},\;p=0.20)$. There was no significant difference in mean duration of respirator usage and 24-hour blood loss after surgery between the two groups. Plasma free Hb was measured lower in the group with $T-PLS^{TM}\;(24.5{\pm}21.7\;mg/dL\;in\;T-PLS^{TM}\;versus\;46.8{\pm}23.0mg/dL\;in\;Bio-pump^{TM},\;p<0.05)$. There was no significant difference in coronary infarction, arrhythmia, renal failure and morbidity rate of cerebrovascular disease. There was a case of death after surgery (death rate of 5%) in the group tested with $T-PLS^{TM}$, but the death rate was not statistically significant. Conclusion: Coronary bypass was operated with $T-PLS^{TM}$ (Pulsatile flow pump) using a heart-lung machine. There was no unexpected event caused by mechanical error during surgery, and the clinical process of the surgery was the same as the surgery for which $Bio-pump^{TM}$ was used. In addition, $T-PLS^{TM}$ used surgery was found to be less detrimental to blood corpuscles than the pulsatile flow has been known to be. Authors of this study could confirm the safety of $T-PLS^{TM}$.

• Journal of Chest Surgery
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• v.30 no.5
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• pp.471-478
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• 1997

Introduction: The use of rabbits as a cardiopulmonary bypass(CPB) animal model is extremely dif%cult mainly due to technical problems. On the other hand, deep hypothermic circulatory arrest(CA) is used to facilitate surgical repair in a variety of cardiac diseases. Although steroids are generally known to be effective in the treatment of cerebral edema, the protective effects of steroids on the brain during CA are not conclusively established. Objectives of this study are twofold: the establishment of CPB technique in rabbits and the evaluation of preventive effect of steroid on the development of brain edema during CA. Material '||'&'||' Methods: Fifteen New Zealan white rabbits(average body weight 3.5kg) were divided into three experimental groups; control CA group(n=5), CA with Trendelenberg position group(n=5), and CA with Trendelenberg position + steroid(methylprednisolone 30 mglkg) administration group(n=5). After anesthetic induction and tracheostomy, a median sternotomy was performed. An aortic cannula(3.3mm) and a venous ncannula(14 Fr) were inserted, respectively in the ascending aorta and the right atrium. The CPB circuit consisted of a roller pump and a bubble oxygenator. Priming volume of the circuit was approximately 450m1 with 120" 150ml of blood. CPB was initiated at a flow rate of 80~85ml/kg/min, Ten min after the start of CPB, CA was established with duration of 40min at $20^{\circ}C$ of rectal temperature. After CA, CPB was restarted with 20min period of rewarming. Ten min after weaning, the animal was sacrif;cod. One-to-2g portions of the following tissues were rapidly d:ssected and water contents were examined and compared among gr ups: brain, cervical spinal cord, kidney, duodenum, lung, heart, liver, spleen, pancreas. stomach. Statistical significances were analyzed by Kruskal-Wallis nonparametric test. Results: CPB with CA was successfully performed in all cases. Flow rate of 60-100 mlfkgfmin was able to be maintained throughout CPB. During CPB, no significant metabolic acidosis was detected and aortic pressure ranged between 35-55 mmHg. After weaning from CPB, all hearts resumed normal beating spontaneously. There were no statistically significant differences in the water contents of tissues including brain among the three experimental groups. Conclusion: These results indicate (1) CPB can be reliably administered in rabbits if proper technique is used, (2) the effect of steroid on the protection of brain edema related to Trendelenburg position during CA is not established within the scope of this experiment.