• 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.

• 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.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.57 no.6
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• pp.557-566
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• 2004

Background : To find out effectiveness of multimodality treatments based on induction chemotherapy(CTx) in patients with clinical stage IIIA NSCLC Methods : From 1997 to 2002, 74 patients with clinical stage IIIA NSCLC underwent induction CTx at the hospital of Chungnam National University. Induction CTx included above two cycles of cisplatin-based regimens(ectoposide, gemcitabine, vinorelbine, or taxol) followed by tumor evaluation. In 30 complete resection group, additional 4500-5000cGy radiotherapy(RTx) was delivered in 15 patients with pathologic nodal metastasis. 29 out of 44 patients who were unresectable disease, refusal of operation, and incomplete resection were followed by 60-70Gy RTx in local treatment. Additional 1-3 cycle CTx were done in case of induction CTx responders in both local treatment groups. Results : Induction CTx response rate were 44.6%(complete remission 1.4% & partial response 43.2%) and there was no difference of response rate by regimens(p=0.506). After induction chemotherapy, only 33 out of resectable 55 ones(including initial resectable 37 patients) were performed by surgical treatment because of 13 refusal of surgery by themselves and 9 poor predicted reserve lung function. There were 30(40.5%) patients with complete resection, 2(2.6%) persons with incomplete resection, and 1(1.3%) person with open & closure. Response rate in 27 ones with chest RTx out of non-operation group was 4.8% CR and 11.9% PR. In complete resection group, relapse free interval was 13.6 months and 2 year recur rate was 52%. In non-complete resection(incomplete resection or non-operation) group, disease progression free interval was 11.2 months and 2 year disease progression rate was 66.7%. Median survival time of induction CTx 74 patients with IIIA NSCLC was 25.1months. When compared complete resection group with non-complete resection group, the median survival time was 31.7 and 23.4months(p=0.024) and the 2-year overall survival rate was 80% and 41%. In the complete resection group, adjuvant postoperative RTx subgroup significantly improved the 2-year local control rate(0% vs. 40%, p= 0.007) but did not significantly improve overall survival(32.2months vs. 34.9months, p=0.48). Conculusion : Induction CTx is a possible method in the multimodality treatments, especially followed by complete resection, but overall survival by any local treatment(surgical resection or RTx) was low. Additional studies should be needed to analysis data for appropriate patient selection, new chemotherapy regimens and the time when should RTx be initiated.

• Journal of Chest Surgery
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• v.39 no.10 s.267
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• pp.739-748
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• 2006

Background: The purpose of this study is to ascertain the neuroprotective effect of cyclosporin A on the 25-min surgical ischemia model in the spinal cords of rabbits with neuropathological correlation and histoimmunochemical analyses, Material and Method: Thirty-two New Zealand white rabbits were randomly divided into four groups: Rabbits were randomly divided into four groups: the control 12 group (n=8), the control 17 group (n=8), the cyclosporin Cs2 group (n=8), and the cyclosporin Cs7 group (n=8). The 12 group underwent a 25-min aortic cross- clamp without intervention and were sacrificed on the 2nd day postoperatively, while the 17 group underwent a 25- min of aortic cross-clamp without intervention and were sacrificed on the 7th day postoperatively. The Cs2 group received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed on the End day postoperatively, while the Cs7 group received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed on the 7th day postoperatively. The rabbits underwent 25-min surgical aortic cross-clamp. Neurologic functions were evaluated on the 2nd day and 7th postoperative day using Tarlov scoring system. After scoring neurologic function, all rabbits were sacrificed for histopathologic observation. Result: All rabbits survived the experimental procedure. The values of Tarlov score did not show any differences between the control and cyclosporin groups on the 2nd day. The scores of group Cs7 ($2.75{\pm}0.89$) were significantly higher than those of group 17 ($1.25{\pm}1.39$) on the 7th day (p<0,05). On the histologic exanminations, specimens of the spinal cord showed necrosis and apoptosis. The pathologic scores of group Cs7 ($1,0{\pm}0.53$) was less than those of group 17 ($2.13{\pm}1.36$, p<0.05). TUNEL staing showed apoptosis of the specimen in group 12 and Cs2 but there was no stastically significant difference between groups on the score. There were more overexpression of HSP70 and nNOS in cyclosporine group than in control group. Conclusion: We think that cyclosporin A may decrease neuronal cell death with induced upregulation of HSP70 against 25-min ischemia of the spiral cord in the rabbit.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.632-643
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• 2004

Background: The Histidine-Tryptophan-Ketoglutarate (HTK) solution has been shown to provide the excellent myocardial protection as a cardioplegia. The HTK solution has relatively low potassium as an arresting agent of myocardium, and low sodium content, and high. concentration of histidine biological buffer which confer a buffering capacity superior to that of blood.. Since HTK solution has an excellent myocardial protective ability, it is reported to protect myocardium from ischemia for a considerable time (120 minutes) with the single infusion of HTK solution as a cardioplegia. The purpose of this study is to evaluate the cardioprotective effect of HTK solution on myocardium when the ischemia is. exceeding 120 minutes at two different temperature (10 to 12$^{\circ}C$, 22 to 24$^{\circ}C$) using the Langendorff apparatus, Material and Method: Hearts from Sprague-Dawley rat, weighing 300 to 340 g, were perfused with Krebs-Henseleit solution at a perfusion pressure of 100 cm $H_2O$. After the stabilization, the heart rate, left ventricular developed pressure (LVDP), and coronary flow were measured. Single dose of HTK solution was infused into the ascending aorta of isolated rat heart and hearts were preserved at four different conditions. In group 1 (n=10), hearts were preserved at deep hypothermia (10∼12$^{\circ}C$) for 2 hours, in group 2 (n=10), hearts were preserved at moderate hypothermia (22∼24$^{\circ}C$) for 2 hours, in group 3 (n=10), hearts were preserved at deep hypothermia for 3 hours, and in group 4 (n=10), hearts were preserved at moderate hypothermia for 3 hours. After the completion of the preservation, the heart rate, left ventricular developed pressure, and coronary flow were measured at 15 minutes, 30 minutes, and 45 minutes after the initiation of reperfusion to assess the cardiac function. Biopsies were also done and mitochondrial scores were counted in two cases of each group for ultrastructural assessment. Result: The present study showed that the change of heart rate was not different between group 1 and group 2, and group 1 and group 3. The heart rate was significantly decreased at 15 minutes in group 4 compared to that of group 1 (p<0.05 by ANCOVA). The heart rate was recovered at 30 minutes and 45 minutes in group 4 with no significant difference compared to that of group 1. The decrease of LVDP was significant at 15 minutes, 30 minutes and 45 minutes in group 4 compared to that of group 1 (p < 0.001 by ANCOVA). Coronary flow was significantly decreased at 15 minutes, 30 minutes, and 45 minutes in group 4 compared to that of group 1 (p < 0.001 by ANCOVA). In ultrastructural assessment, the mean myocardial mitochondrial scores in group 1, group 2, group 3, and group 4 were 1.02$\pm$0.29, 1.52$\pm$0.26, 1.56$\pm$0.45, 2.22$\pm$0.44 respectively. Conclusion: The HTK solution provided excellent myocardial protection regardless of myocardial temperature for 2 hours. But, when ischemic time exceeded 2 hours, the myocardial hemodynamic function and ultrastructural changes were significantly deteriorated at moderate hypotherma (22∼ 24$^{\circ}C$). This indicates that it is recommended to decrease myocardial temperature when myocardial ischemic time exceeds 2 hours with single infusion of HTK solution as a cardioplegia.

• Journal of Chest Surgery
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• v.41 no.2
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• pp.202-209
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• 2008

Background: The introduction of Drug Eluting Stents (DES) decreased the number of patients referred for coronary artery bypass grafting (CABG). The impact of DES on CABG (Step 1) was studied and compared with the 1-year outcome after CABG with DES (Step 2). Material and Method: Surgical results for patients who underwent off-pump CABG (OPCAB) before the introduction of DES(n=298) were compared with those who underwent OPCAB after the introduction of DES (n=288) (Step 1). Postoperative 30-day and 1-year results were also compared between the patients who underwent percutaneous coronary intervention (PCI) using DES (n=220) and those who underwent OPCAB (n=255) (Step 2). Result: Since the introduction of DES, the ratio of CABG versus PCI decreased. In the CABG group, the number of high risk patients such as elderly patients (age 62 vs. 64, p=0.023), those with chronic renal failure (4% vs. 9%, p=0.021), calcification of the ascending aorta (9% vs. 15%, p=0.043), or frequency of urgent or emergent operations (12% vs. 22%, p=0.002) increased. However, there were no differences in the cardiac death and graft patency rates between the two groups (step 1). During the one-year follow up period, the rate of target vessel revascularization (12.3% vs. 2.4%, p<0.001) and major adverse cardiac events (MACE: death, myocardial infarct, TVR) were higher in the DES than the CABG group (13.6% vs 4.3%) (stage 2). Conclusion: Introduction of DES decreased the number of patients referred for surgery, and increased the comorbidity in patients who underwent CABG. DES increased the rate of target vessel revascularization, and the occurrence of MACE during the 1-year follow-up. However, there was no difference in the incidence of myocardial infarction and cardiac death between the two groups.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.478-486
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• 2000

Background : In acute lung injury, alveolar macrophages play a pivotal role in the inflammatory process during the initiation phase and in the reconstruction and fibrosis process during the later phase. Recently, it has been proven that alveolar macrophages are constituted by morphologically, biochemically and immunologically heterogenous cell subpopulations. The possibility of alterations to these characteristics of the alveolar macrophage population during lung disease has been raised. To investigate such a possibility a hyperoxic rat lung model was made to check the distributional and morphological changes of rat alveolar macrophage subpopulation in acute hyperoxic lung injury. Method : Alveolar macrophage were lavaged from normal and hyperoxic lung injury rats and separated by discontinuous gradients of percoll. After cell counts of each density fraction were accessed, the morphomeric analysis of alveolar macrophages was performed on cytocentrifuged preparations by transmission electron micrograph. Result : 1. The total alveolar macrophage cell count significantly increased up to 24 hours after hyperoxic challenge (normal control group $171.6{\pm}24.1{\times}10^5$, 12 hour group $194.8{\pm}17.9{\times}10^5$, 24 hour group $207.6{\pm}27.1{\times}10^5$, p<0.05). oHoHH However the 48 hour group ($200.0{\pm}77.8{\times}10^5$) did not show a significant difference. 2. Alveolar septal thickness significantly increased up to 24 hours after hyperoxic challenge(normal control group $0.7{\pm}0.2{\mu}m$, 12 hour group $1.5{\pm}0.4{\mu}m$, 24 hour group $2.3{\pm}0.4{\mu}m$, p<0.05). However the 48 hour group did not show further change ($2.5{\pm}0.4{\mu}m$). Number of interstitial macrophage markedly increased at 24 hour group. 3. Hypodense fraction(fraction 1 and fraction 2) of alveolar macrophage showed a significant increase following hyperoxic challenge ($\beta=0.379$.$\beta=0.694$. p<0.05) ; however, fraction 3 was rather decreased following the hyperoxic challenge($\beta=0.815$. p<0.05), and fraction 4 showed an irregular pattern. 4. Electron microscopic observation of alveolar macrophage from each fraction revealed considerable morphologic heterogeneity. Cells of the most dense subfraction(fraction 4) were small, round, and typically highly ruffled with small membrane pseudopods. Cells of the least dense fraction (fraction 1) were large and showed irregular eccentric nucleus and high number of heterogenous inclusions. Conclusion : In conclusion, these results suggest that specific hypodense alveolar macrophage subpopulation may play a an important role in an acute hyperoxic lung injury model But further study, including biochemical and immunological function of these subpopulations, is needed.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.391-400
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• 1997

Background : Bronchoscopy is an essential procedure for identifying the bleeding site and evaluating cause of hemoptysis. However, it is controversial regarding to the timing of bronchoscopy in patients with hemoptysis. Early bronchoscopy, which was performed during hemoptysis or with 48hour after cessation of bleeding, was better for identifying the site of bleeding compared with delayed bronchoscopy, which was performed 48 hours after cessation of bleeding. The diagnostic yield of identifying the bleeding site by bronchoscopy was variable in reported literature and the safety of early bronchoscopy was not mentioned in previous literature. Therefore, we evaluated the efficacy and safety of early bronchoscopy in patients with hemoptysis. Method : From October 1994 to August 1996 in Samsung Medical Center, bronchoscopy was performed in patients with hemoptysis. Early bronchoscopy was performed prospectively during hemoptysis or within 48 hours after cessation of bleeding from May 1995 to August 1996. Delayed bronchoscopy group included patients who did not received early bronchoscopy at the same period or in whom bronchoscopy was performed 48 hour after cessation of bleeding from October 1994 to May 1995. Results : Early bronchoscopy group was performed 73 times in 71 patients. Delayed bronchoscopy was performed in 57 times in 55 patients. There was no difference as to amount and underlying cause of hemoptysis between both groups. Indentification of bleeding site by visualizing active bleeding was significantly higher in early bronchoscopy (38.3%) than delayed bronchoscopy group (8.7%)(p < 0.05). Indentification of bleeding site by bleeding after clot removal was 8 in early and 10 in delayed bronchoscopy. Indentification of bleeding site by visualizing active bleeding and bleeding after clot removal was 36 in early and 15 patients in delayed bronchoscopy(p > 0.05). Causes of hemoptysis was found in 18 patients in early and 16 patients in delayed bronchoscopy group. patients who had early bronchoscopy underwent surgery. We diagnosed the site of bleeding in 4 patients preoperatively. In 3 patients we made a treatment plan promptly right after bronchoscopy. Among early bronchoscopy group, bleeding over 100cc during bronchoscopy occurred in 2 patients. In early bronchoscopy group there was no other major complication during bronchoscopy. Conclusion : In patients with hemoptysis, early bronchoscopy which performed within 48 hours after cessation of bleeding was more effective procedure for identifying the bleeding site than delayed bronchoscopy which was performed after 48 hour cessation of bleeding.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.945-953
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• 1996

Background : Many acute and chronic lung diseases including pneumoconiosis are characterized by the presence of increased numbers of activated macrophages. These macrophages generate several inflammatory cell chemoattractants, by which neutrophil migrate from vascular compartment to the alveolar space. Recruited neutrophils secrete toxic oxygen radicals or proteolytic enzymes and induce inflammatory response. Continuing inflammatory response results in alteration of the pulmonary structure and irreversible fibrosis. Recently, a polypeptide with specific neutrophil chemotactic activity, interleukin-8(IL-8), has been cloned and isolated from a number of cells including : monocytes, macrophages and fibroblasts. IL-1 and/or TNF-${\alpha}$ preceded for the synthesis of IL-8, and we already observed high level of IL-1 and TNF-${\alpha}$ in the pneumoconioses. So we hypothesized that IL-8 may be a central role in the pathogenesis of pneumoconiosis. In order to evaluate the clinical utility of IL-8 as a biomarker in the early diagnosis of pneumoconiosis, we investigated the increase of IL-8 in the pneumoconiotic patient and the correlation between IL-8 level and progression of pneumoconiosis. Method : We measured IL-8 in the serum of 48 patients with pneumoconiosis and 16 persons without dust exposure history as a control group. Pneumoconiotic cases were divided into 3 groups according to ILO Classification : suspicious group(n=16), small opacity group(n=16) and large opacity group(n=16). IL-8 was measured by a sandwich enzytne immunoassay technique. All data were expressed as the $mean{\pm}standard$ deviation. Results: 1) The mean value of age was higher in the small opacity and large opacity group than comparison group, but smoking history was even. Duration of dust exposure was not different among 3 pneumoconiosis groups. 2) IL-8 level was $70.50{\pm}53.63pg/m{\ell}$ in the suspicious group, $107.50{\pm}45.88pg/m{\ell}$ in the small opacity group, $132.50{\pm}73.47pg/m{\ell}$ in the large opacity group and $17.85{\pm}33.85pg/m{\ell}$ in the comparison group. IL-8 concentration in all pneumoconiosis group was significant higher than that in the comparison group(p<0.001). 3) IL-8 level tended to increase with the progression of pneumoconiosis. Multiple comparison test using Anova/Scheffe analysis showed a significant difference between suspicious group and large opacity group(p<0.05). 4) The level of IL-8 was correlated with the progression of pneumoconiosis(r=0.4199, p<0.05). Conclusion : IL-8 is thought to be a good biomarker for the early diagnosis of pneumoconiosis.