• Journal of Chest Surgery
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• v.39 no.7 s.264
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• pp.534-543
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• 2006

Background: There are a lot of debates regarding the optimal timing of operation of acute myocardial infarction (AMI). Off pump coronary artery bypass grafting (OPCAB) has benefits by avoiding the adverse effects of the cardio-pulmonary bypass, but its efficacy in AMI has not been confirmed yet. The purpose of this study is to evaluate retrospectively early and mid-term results of OPCAB in patients with AMI according to transmurality and timing of operation. Material and Method: Data were collected in 126 AMI patients who underwent OPCAB between January 2002 and July 2005, Mean age of patients were 61.2 years. Male was 92 (73.0%) and female was 34 (27.2%). 106 patients (85.7%) had 3 vessel coronary artery disease or left main disease. Urgent or emergent operations were performed in 25 patients (19.8%). 72 patients (57.1%) had non-transmural myocardial infarction (group 1) and 52 patients (42.9%) had transmural myocardial infarction (group 2). The incidence of cardiogenic shock and insertion of intra-aortic balloon pump (IABP) was higher in group 2. The time between occurrence of AMI and operation was divided in 4 subgroups (<1 day, $1{\sim}3\;days,\;4{\sim}7\;days$, >8 days). OPCAB was performed a mean of $5.3{\pm}7.1$ days after AMI in total, which was $4.2{\pm}5.9$ days in group 1, and $6,6{\pm}8.3$ days in group 2. Result: Mean distal an-astomoses were 3.21 and postoperative IABP was inserted in 3 patients. There was 1 perioperative death in group 1 due to low cardiac output syndrome, but no perioperative new MI occurred in this study. There was no difference in postoperative major complication between two groups and according to the timing of operation. Mean follow-up time was 21.3 months ($4{\sim}42$ months). The 42 months actuarial survival rate was $94.9{\pm}2.4%$, which was $91.4{\pm}4.7%$ in group 1 and $98.0{\pm}2.0%$ in group 2 (p=0.26). The 42 months freedom rate from cardiac death was $97.6{\pm}1.4%$ which was $97.0{\pm}2.0%$ in group 1 and $98.0{\pm}2.0%$ in group 2 (p=0.74). The 42 months freedom rate from cardiac event was $95.4{\pm}2.0%$ which was $94.8{\pm}2.9%$ in group 1 and $95.9{\pm}2.9%$ in group 2 (p=0.89). Conclusion: OPCAB in AMI not only reduces morbidity but also favors hospital outcomes irrespective of timing of operation. The transmurality of myocardial infarction did not affect the surgical and midterm outcomes of OPCAB. Therefore, there may be no need to delay the surgical off-pump revascularization of the patients with AMI if surgical revascularization is indicated.

• Journal of Chest Surgery
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• v.35 no.7
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• pp.523-529
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• 2002

Background: Previous reports present that the early results of coronary artery bypass grafting (CABG) has been improving with the accumulation of surgical experience. We conducted a retrospective analysis of the patients who received CABG to evaluate the recent results of CABG. Material and Method: Between January 1996 and August 2001, 154 patients underwent CABG at Hanyang University Hospital. There were 47 patients(group I) who were operated between 1996 and 1998, and 107 patients(group II) who were operated thereafter. The preoperative diagnosis, operative procedure, mortality, and complications were analyzed retrospectively. Result: There were 35 males and 12 females in group I, and 78 males and 29 females in group II, which shows similar ratio of sexes between the two groups. The average age of patients for group I and group II was $55.9{\pm}6.2$ years and $61.0{\pm}8.0$ years, respectively, showing a significant increase in group II(p<0.05). The average left ventricular ejection fraction(LVEF) for group I and group II was $54.6{\pm}11.8$% and $56.9{\pm}13.0$%, respectively. The number of patients who had previous MI in group I and group II were 13 patients(27.7%) and 14 patients(13.1%), respectively, which shows a significant difference (p<0.05). All procedures were performed using the cardiopulmonary bypass(CPB) and moderate systemic hypothermia. Myocardial protection was achieved using intermittent hypothermic ischemia under ventricular fibrillation state or cold crystalloid cardioplegic solution for most of group I patients, whereas cold blood cardioplegic solution was used for group II patients. The mean CPB times for group I and group II were $149.2{\pm}48.7$ minutes and $113.1{\pm}30.6$ minutes, respectively. The mean aortic cross clamp times for group I and group II were $81.3{\pm}26.5$ minutes $72.2{\pm}23.9$ minutes, respectively. These figures show that CPB and aortic cross clamp times were significantly reduced in group II(p<0.05). The use of the left internal thoracic artery(LITA) was increased from 42%(20/47) for group I to 81% (87/107) for group II. The mean number of grafts also significantly increased from $2.5{\pm}0.6$ for group I to $3.0{\pm}1.1$ for group II(p<0.05). Intra-aortic balloon pump(IABP) was applied in 7 cases in group I and 17 cases in group II. Of these, 28.6%(2/7) and 52.9%(9/17) were broadly applied preoperatively in patients with LVEF<40% or congestive heart failure. The operative mortalities for group I and II were 10.6%(5/47) and 0.9%(1/107), respectively, which shows significant decrease for group II(p.0.05). Conclusion: This report suggest that CABG using CPB can recently be performed more safely in virtue of the accumulation of surgical experience with reduction in CPB and aortic cross clamp times and improved surgical techniques and myocardial protection. And we think that the optimal treatment of patients with left ventricular dysfunction associated with congestive heart failure and the extended application of IABP, especially have contributed to the reduction of operative mortality and morbidity.

• Journal of Chest Surgery
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• v.40 no.4 s.273
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• pp.264-272
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• 2007

Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.

• Journal of Chest Surgery
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• v.40 no.4 s.273
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• pp.280-287
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• 2007

Background: We retrospectively evaluated the clinical results of surgically managing patients with Ebstein's anomaly. Material and Method: Between Feb. f 984 and June 2006, 50 patients who underwent surgical treatment for Ebstein's anomaly at Yonsei Cardiovascular Center were retrospectively reviewed. The mean age of the patients was 26.9 years and 19 patients were male, Associated anomalies included atrial septal defect (33), patent ductus arteriosus (2), ventricular septal defect (1), and pulmonary stenosis (4), and 90%, (45/50) of the patients had more than a moderate degree of tricuspid regurgitation. Carpentier type A was present in 6 patients, type B in 26, type C in 14 and type D in 4. Ten patients were associated with WPW syndrome. Conservative surgery was possible in 31 patients (tricuspid annuloplasty, plication of the atrialized RV), Fontan's operation was peformed in 4 patients, tricuspid valve replacement was done in 12 and palliative surgery was done in 2 patients. Thirteen patients were associated with hi-directional cavopulmonary shunt (BCPS: one and a half ventricular repairs): 10 patients with WPW syndrome and 4 patients with atrial fibrillation underwent concomitant ablation. Result: The postoperative median NYHA functional class $(3{\rightarrow}1)$ and the mean cardio-thoracic ratio $(0.65{\rightarrow}0.59)$ were decreased significantly (p<0.001, p=0.014). The mean oxygen saturation $(86.6{\rightarrow}94.1%)$, and median TR grade $(4{\rightarrow}1)$ were also significantly improved (p=0.004, p<0.001). For comparison of BCPS and conservative surgery, the preoperative right ventricular pressure (33.0 vs. 41.3 mmHg), the ICU stay (2.80 vs. 1.89 days), the hospital say (10.6 vs. 16.8 days), and the left ventricular ejection fraction (64.3 vs. 72.8%) were statistically different. Postoperative mortality occurred in 3 patients (6%) due to biventricular failure in 2 patients and sepsis in the other patient. The mean follow up duration was 101.5 months, and one patient died of Fontan failure and 6 patients required reoperation (bioprosthetic degenerative change (2) and Fontan conversion (4)). The overall survival rate at 10 years was 90.2%, the freedom from reoperation rate and rate of cardiac related events were 78.9% and 49.2%, respectively. Conclusion: Surgical management of Ebstein's anomaly can be performed safely, and the associated BCPS may be helpful for high-risk patients. Adequate application of surgical management may increase the long-term survival with a reduced rate of reoperation.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.624-629
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• 2009

Background: Making the histologic diagnosis of small pulmonary nodules and ground glass opacity (GGO) lesions is difficult. CT-guided percutaneous needle biopsies often fail to provide enough specimen for making the diagnosis. Video-assisted thoracoscopic surgery (VATS) can be inefficient for treating non-palpable lesions. Preoperative localization of small intrapulmonary lesions provides a more obvious target to facilitate performing intraoperative. resection. We evaluated the efficacy of CT-guided localization with using a hook wire and this was followed by VATS for making the histologic diagnosis of small intrapulmonary nodules and GGO lesions. Material and Method: Eighteen patients (13 males) were included in this study from August 2005 to March 2008. 18 intrapulmonary lesions underwent preoperative localization by using a CT-guided a hook wire system prior to performing VATS resection for intrapulmonary lesions and GGO lesions. The clinical data such as the accuracy of localization, the rate of conversion-to-thoracotomy, the operation time, the postoperative complications and the histology of the pulmonary lesion were retrospectively collected. Result: Eighteen VATS resections were performed in 18 patients. Preoperative CT-guided localization with a hook-wire was successful in all the patients. Dislodgement of a hook wire was observed in one case. There was no conversion to thoracotomy, The median diameter of lesions was 8 mm (range: $3{\sim}15\;mm$). The median depth of the lesions from the pleural surfaces was 5.5 mm (range: $1{\sim}30\;mm$). The median interval between preoperative CT-guided with a hook-wire and VATS was 34.5 min (range: ($10{\sim}226$ min). The median operative time was 43.5.min (range: $26{\sim}83$ min). In two patients, clinically insignificant pneumothorax developed after CT-guided localization with a hook-wire and there were no other complications. Histological examinations confirmed 8 primary lung cancers, 3 cases of metastases, 3 cases of inflammation, 2 intrapulmonary lymph nodes and 2 other benign lesions. Conclusion: CT-guided localization with a hook-wire followed by VATS for treating small intrapulmonary nodules and GGO lesions provided a low conversion thoracotomy rate, a short operation time and few localization-related or postoperative complications. This procedure was efficient to confirm intrapulmonary lesions and GGO lesions.

• Journal of Food Hygiene and Safety
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• v.20 no.2
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• pp.118-122
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• 2005

Immu-Forte (Dong-Ahm Bio's. Corp., Korea) was evaluated fir its effectiveness as a nonspecific immunostimulator in mice. The effects of Immu-Forte were determined by analysis of cytokines using ELISh and phenotype of leukocyte subpopulations using monoclonal antibodies specific to mouse leukocyte differentiation antigens and flow cytometry. CD4 T cells, CD8 T cells, macrophages, IL-12 and IFN-r in Immu-Forte EX-treated middle dose group increased in 3 months posttreatment and were significantly higher (p<0.05) than that of control at 3 months posttreatment. All T cells, all B cells, macrophages, IL-2, IL-4 and IL-12 in Immu-Forte EX-treated low dose uoup increased in 3 months posttreatment and were significantly higher (p<0.05) than that of control at 3 months posttreatment. In the Immu-Forte soy-treated group, CD4 T cells, IL-2, IL-4 and IL-12 were significantly higher in high dose-treated group, and CD 4 T cell, macrophages, IL-2, IL-4 and IL-12 were significantly higher in middle dose-treated group, and all T cell, IL-2, IL-4 and IL-12 were significantly higher in low dose-treated group. In the Itnmu-Forte A-treated group, macrophages, m cells and IL-12 in high dose-treated group and all T cells, macrophages, NK cells, IL-2, IL-4 and IL-12 in middle dose-treated group and NK cells in low dose-treated group were significantly higher (p<0.05) than that of control at 3 months posttreatment. In the Immu-Forte F-treated Group, all B cells, IL-4 and IL-12 in high dose-treated group and all T cells, aBl B cells, CD 4 T cells, CD8 T cells, macrophage, IL-2, IL-4, IL-12 and IFN-r in middle dose-treated group and NK cells and IL-12 in low dose-treated group were significantly higher (p<0.05) than that of control at 3 months posttreatment. In conclusion, the study has demonstrated that Immu-Forte had an immunostimulatory effect on mice through proliferation and activation of mouse immune cells.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.486-494
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• 2000

Background : The dominant innervation of airway smooth muscle is parasympathetic fibers which are carried in the vagus nerve. Activation of these cholinergic nerves releases acetylcholine which binds to $M_3$ muscarinic receptors on the smooth muscle causing bronchocontraction. Acetylcholine also feeds back onto neuronal $M_2$ muscarinic receptors located on the postganglionic cholinergic nerves. Stimulation of these receptors further inhibits acetylcholine release, so these $M_2$, muscarinic receptors act as autoreceptors. Loss of function of these $M_2$ receptors, as it occurs in animal models of hyperresponsiveness, leads to an increase in vagally mediated hyperresponsiveness. However, there are limited data pertaining to whether there are dysfunctions of these receptors in patients with asthma. The aim of this study is to determine whether there are dysfunction of $M_2$ muscarinic receptors in asthmatic patients and difference of function of these receptors according to severity of asthma. Method : We studied twenty-seven patients with asthma who were registered at Pulmonology Division of Korea University Hospital. They all met asthma criteria of ATS. Of these patients, eleven patients were categorized as having mild asthma, eight patients moderate asthma and eight patients severe asthma according to severity by NAEPP Expert Panel Report 2(1997). All subjects were free of recent upper respiratory tract infection within 2 weeks and showed positive methacholine challenge test ($PC_{20}$<16mg/ml). Methacholine provocation tests were performed twice on separate days allowing for an interval of one week. In the second test, pretreatment with the $M_2$ muscarinic receptor agonist pilocarpine($180{\mu}g$) through inhalation was performed be fore the routine procedures. Results : Eleven subjects with mild asthma and eight subjects with moderate asthma showed significant increase of $PC_{20}$ from 5.30$\pm$5.23mg/ml(mean$\pm$SD) to 20.82$\pm$22.56mg/ml(p=0.004) and from 2.79$\pm$1.51mg/ml to 4.67$\pm$3.53mg/ml(p=0.012) after pilocarpine inhalation, respectively. However, in the eight subjects with severe asthma significant increase of $PC_{20}$ from l.76$\pm$1.50mg/ml to 3.18$\pm$4.03mg/ml(p=0.161) after pilocarpine inhalation was not found. Conclusion : In subjects with mild and moderate asthma, function of $M_2$ muscarinic receptors was normal, but there was a dysfunction of these receptors in subjects with severe asthma. ηlese results suggest that function of $M_2$ muscarinic receptors is different according to severity of asthma.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.332-342
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• 2000

Background : The importance of pro-inflammatory cytokines, especially tumor necrosis factor $\alpha$ (INF-$\alpha$) and interleukin-1$\beta$ (IL-1$\beta$), have been extensively documented in the generation of inflammatory lung disease. Lung epithelial cells are also actively involved in initiating and maintaining inflammation by producing pro-inflammatory mediators. Understanding the mechanism of pro-inflammatory cytokine expression in lung epithelial cells is crucial to the development of new therapeutic modalities for inflammatory lung disease. Transcription of most pro-inflammatory cytokines is dependent on the activation of NF-${\kappa}B$. However, the relationship between pro-inflammatory cytokine expression and NF-${\kappa}B/I{\kappa}B$ pathway in lung epithelial cells is not clear. Methods : BEAS-2B, A549, Na-H157, NCI-H719 cells were stimulated with IL-$1{\beta}$ or TNF-$\alpha$ at various times, and then IL-8 and TNF-$\alpha$mRNA expressions were assayed by Northern blot analysis. IL-$1{\beta}$ or TNF-$\alpha$-induced NF-${\kappa}B$ activation was assessed by the nuclear translocation of p65 NF-${\kappa}B$ subunit. The degradation of $I{\kappa}B{\alpha}$ and $I{\kappa}B{\beta}$ by IL-$1{\beta}$ or TNF-$\alpha$stimulation was assayed by Western blot analysis. The phosphorylation of $I{\kappa}B{\alpha}$ was evaluated by Western blot analysis after pre-treating cells with proteasome inhibitor followed by IL-$1{\beta}$ or TNF-$\alpha$ stimulation. The basal level of IKK $\alpha$ expression was evaluated by Western blot analysis. Results: $I{\kappa}B{\alpha}$ and $I{\kappa}B{\alpha}$ was rapidly degraded after 5 minutes of incubation with IL-$1{\beta}$ or TNF-$\alpha$ in BEAS-2B, A549, and NCI-H157 cells. The activation of NF-${\kappa}B{\alpha}$ and the induction of IL-8 and TNF-$\alpha$ mRNA expression were observed by IL-$1{\beta}$ or TNF-$\alpha$ stimulation in these cells. In contrast, neither the changes in NF-${\kappa}B/I{\kappa}B$ pathway nor IL-8 and TNF-$\alpha$mRNA expression was induced by IL-$1{\beta}$ or TNF-$\alpha$ stimulation in NCI-H719 cells. IL-$1{\beta}$ and TNF-$\alpha$-induced $I{\kappa}B$ phosphorylation was observed in BEAS-2B, A549, and NCI-H157 cells, but not in NCI-H719 cells. The basal level of IKK$\alpha$ expression was not different between cell. Conclusion : NF-${\kappa}B/I{\kappa}B$ pathway plays an important role in the expression of pro-inflammatory cytokine in most lung epithelial cells. The absence of the effect on NF-${\kappa}B/I{\kappa}B$ pathway in NCI-H719 cells sæms to be due to the defect in the intracellular signal transduction pathway upstream to IKK.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.441-452
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• 2000

Background : It is well known that the prevalence of lung cancer is higher in idiopathic pulmonary fibrosis (IPF) patients than in the general population. This high prevalence is explained by the concept of 'scar carcinoma'. There have been several reports on the prevalence of histologic typo of lung cancer in IPF with conflicting results. Despite of the high smoker rate in almost all previous reports, none considered the smoking history of patients. Therefore we performed a separate studies on fibrosis associated lung cancer and smoking associated lung cancer. The purpose of this study is to investigate the proportion of lung cancer in IPF that is fibrosis associated and to determine the most common histologic type in fibrosis associated lung cancer in IPF. Method : A retrospective review of medical records and radiologic studies was performed for cases of lung cancer with IPF. We investigated smoking history, sequence of diagnosis of lung cancer and IPF, histologic type of lung cancer and the cancer location, especially whether the location is associated with fibrosis. To evaluate the proportion of fibrous associated lung cancer, the lung cancer in IPF were categorized according to the presence of fibrosis at cancer location. Results : Fifty seven patients were subjects for this analysis. Six (11%) cases were diagnosed as lung cancer during follow-up for IPF, and both diseases were diagnosed simultaneously in the others. Ninety four percent of patients were smokers and the average smoking amount was 47.1$\pm$21.9 pack-year. Among the patients with IPF and lung cancer, 42(80.8%) cases were considered as "fibrosis associated". The remainder was "not fibrosis associated" and probably was due to smoking etc. Although the most frequent histologic type was squamous cell carcinoma as a whole, adenocarcinoma was the prominent histologic type in "fibrosis associated lung cancer." Conclusion : Considering the proportion of "fibrosis not associated lung cancer" in the patients with IPF and lung cancer, significant proportion of lung cancer in IPF may not be fibrosis induced. This may influence the distribution of histologic type of lung cancer in IPF.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.87-96
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• 1994

Background : Since tumor necrosis factor was discovered in 1975, TNF has been well known about its cytotoxic effect on tumor cells in vivo and in vitro. According to the recent improvement of molecular biological techinques, it is possible that exogenous TNF gene is transferred to tumor cells and is expressed in theirs. By virtue of TNF gene transfer, we have expected that TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells in vivo without systemic side effect. The expected mechanisms in which antitumor effects of TNF expressed in TNF-gene-transferred tumor cells are working would be as followings. In the first mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells around(like homicide). In the second mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill themselves(like suicide). In the third mechanism, TNF expressed in TNF-gene-transferred tumor cells would recruit immune effector cells and kill tumor cells indirectly. In the last mechanism, TNF expressed in TNF-gene-transferred tumor cells would augment cytokine such as interferon-$\gamma$ to kill tumor cells. Among these four mechanisms of antitumor effect, only the second mechanism has not been established yet. Therefore, to elucidate the second mechanism, We performed this study. Method : We transferred TNF-$\alpha$ gene to NCI-H2058, a human mesothelioma cell line and WEHI164, a murine fibrosarcoma cell line by using retroviral vector(pLT12SNTNF). And, We determined by using MTT assay whether TNF expressed in TNF-gene-transferred tumor cell lines would kill themselves like suicide or not. Then, if TNF-gene-transferred tumor cell lines would not suicide themselves, I would know more about the TNF sensitivity of TNF-gene-transferred tumor cell lines to exogenous TNF also by MTT assay. Result : NCI-H2058 and WEHI164 which were sensitive to TNF, became far less sensitive to endogenous and exogenous TNF after being transferred TNF-$\alpha$ gene to. Conclusion : TNF-gene-transfer to NCI-H2058 and WEHI164 gave them resistance to TNF.