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Development of Porcine Pericardial Heterograft for Clinical Application (Microscopic Analysis of Various Fixation Methods) (돼지의 심낭, 판막을 이용한 이종이식 보철편의 개발(고정 방법에 따른 조직학적 분석))

  • Kim, Kwan-Chang;Choi, Chang-Hyu;Lee, Chang-Ha;Lee, Chul;Oh, Sam-Sae;Park, Seong-Sik;Kim, Woong-Han;Kim, Kyung-Hwan;Kim, Yong-Jiin
    • Journal of Chest Surgery
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    • v.41 no.3
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    • pp.295-304
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    • 2008
  • Background: Various experimental trials for the development of bioprosthetic devices are actively underway, secondary to the limited supply of autologous and homograft tissue to treat cardiac diseases. In this study, porcine bioprostheses that were treated with glutaraldehyde (GA), ethanol, or sodium dodecylsulfate (SDS) were examined with light microscopy and transmission electron microscopy for mechanical and physical imperfections before implantation, Material and Method: 1) Porcine pericardium, aortic valve, and pulmonary valve were examined using light microscopy and JEM-100CX II transmission electron microscopy, then compared with human pericardium and commercially produced heterografts. 2) Sections from six treated groups (GA-Ethanol, Ethanol-GA, SDS only, SDS-GA, Ethanol-SDS-GA and SDS-Ethanol-GA) were observed using the same methods. Result: 1) Porcine pericardium was composed of a serosal layer, fibrosa, and epicardial connective tissue. Treatment with GA, ethanol, or SDS had little influence on the collagen skeleton of porcine pericardium, except in the case of SDS pre-treatment. There was no alteration in the collagen skeleton of the porcine pericardium compared to commercially produced heterografts. 2) Porcine aortic valve was composed of lamina fibrosa, lamina spongiosa, and lamina ventricularis. Treatment with GA, ethanol, or SDS had little influence on these three layers and the collagen skeleton of porcine aortic valve, except in the case of SDS pre-treatment. There were no alterations in the three layers or the collagen. skeleton of porcine aortic valve compared to commercially produced heterografts. Conclusion: There was little physical and mechanical damage incurred in porcine bioprosthesis structures during various glutaraldehyde fixation processes combined with anti-calcification or decellularization treatments. However, SDS treatment preceding GA fixation changed the collagen fibers into a slightly condensed form, which degraded during transmission electron micrograph. The optimal methods and conditions for sodium dodecylsulfate (SDS) treatment need to be modified.

Outcomes of Combined Mitral Valve Repair and Aortic Valve Replacement (대동맥판막 치환술과 동반시행한 승모판막 성형술 결과)

  • Baek, Man-Jong;Na, Chan-Young;Oh, Sam-Se;Kim, Woong-Han;Whang, Sung-Wook;Lee, Cheol;Chang, Yun-Hee;Jo, Won-Min;Kim, Jae-Hyun;Seo, Hong-Ju;Kim, Soo-Cheol;Lim, Cheong;Kim, Wook-Sung;Lee, Young-Tak;Choi, Hyun-Seok;Moon, Hyun-Soo;Park, Young-Kwan;Kim, Chong-Whan
    • Journal of Chest Surgery
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    • v.36 no.7
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    • pp.463-471
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    • 2003
  • The long-term results of combined mitral valve repair and aortic valve replacement (AVR) have not been well evaluated. This study was performed to investigate the early and long-term results of mitral valve repair with AVR. Material and Method: We retrospectively reviewed 45 patients who underwent mitral valve repair and AVR between September 1990 and April 2002. The average age was 47 years: 28 were men and 17 women. Twelve patients had atrial fibrillation and three had a previous cardiac operation. The mitral valve disease consisted of pure insufficiency (MR) in 34 patients, mitral stenosis (MS) in 3, and mixed lesion in 8. Mitral valve disease was due to rheumatic origin in 24 patients, degenerative in 11, annular dilatation in 8, and ischemia or endocarditis in 2. The functional anatomy of mitral valve was annular dilatation in 31 patients, chordal elongation in 19, leaflet thickening in 19, commissural fusion in 13, chordal fusion in 10, chordal rupture in 6, and so on. Aortic prostheses used included mechanical valve in 32 patients, tissue valve in 12, and pulmonary autograft in one. The techniques of mitral valve repair included annuloplasty in 32 patients and various valvuloplasty of 54 techniques in 29 patients. Total cardiopulmonary bypass and aortic cross clamp time were 204$\pm$62 minute and 153$\pm$57 minutes, respectively. Result: Early death was in one patient due to low output syndrome (2.2%). After follow up of 57$\pm$37 months, late death was in one patient and the actuarial survival at 10 years was 96$\pm$4%. Recurrent MR developed grade II or III in 11 patients and moderate MS in 3. Three patients required reoperation for valve-related complications. The actuarial freedom from recurrent MR, MS, and reoperation were 64$\pm$11%, 86$\pm$8%, and 89$\pm$7% respectively. Conclusion: Combined mitral valve repair with AVR offers good early and long-term survival, and adequate techniques and selection of indication of mitral valve repair, especially in rheumatic disease, are prerequisites for better long-term results.

Tracheal gas insufflation (TGI) in patients with increased deadspace fraction: the effect and its determining factors (사강호흡율이 증가된 환자에서 기관내 가스주입법(Tracheal Gas Imsufflation)이 가스교환에 미치는 효과와 그 결정인자)

  • Lim, Chae Man;Jung, Bok Hyun;Koh, Youn Suck;Lee, Sang Do;Kim, Woo Sung;Park, Pyung Hwan;Kim, Dong Soon;Kim, Won Dong
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.1
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    • pp.136-145
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    • 1997
  • Background : Tracheal Gas Insufflation (TGI) is one of the newer ancillary measures in mechanical ventilation employed to enhance carbon dioxide elimination. TGI exerts its effect through reduction of deadspace ventilation, but the factors determining its effect are not well studied yet. Method : The subjects were seven mechanically-ventilated patients ($58.8{\pm}10.6$ yrs) who showed increased physiologic deadspace greater than 60%. After 30 nun of stabilization with 100% oxygen on pressure control ventilation, continuous flow TGI was administered via the insufflation lumen of Hi-Lo Jet Tracheal Tube (Mallincrodt, USA) for 15 min at 3 L/min and 5 L/min each. Results : $PaCO_2$ was decreased ($51.4{\pm}17.6$ at baseline, $49.1{\pm}18.9$ at TGJ 3 L/min $45.0{\pm}14.9$ mm Hg at TGI 5 L/min, p=0.050), and pH was increased ($7.37{\pm}0.12$, $7.38{\pm}0.13$, $7.39{\pm}0.12$, respectively, p=0.037) while mixed expired $CO_2$ ($P_ECO_2$) was not changed significantly from baseline (p=0.336) by TGI. Physiologic deadspace(Vdphy) was decreased ($73.0{\pm}7.9$% at baseline, $69.8{\pm}10.0$% at TGI 3 L/min, and $67.1{\pm}10.1$% at TGI 5 L/min, p=0.015). $AaDO_2$(p=0.147), Vt(p=0.2140), Pmean(p=0.7788) and mean arterial pressure(p=0.4169) were not changed. The correlation between % maximal decrease of Vdphy were r=0.790 with the ratio of baseline Vdana/Vdphy(p=0.035) and r=-0.754 with baseline Vdalv(p=0.050). Conclusion: TGI was effective in reducing $PaCO_2$ and deadspace, and the deadspace-reducing effect was best correlated with baseline anatomic/physiologic deadspace ratio.

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Diffuse Panbronchiolitis : Clinical Significance of High-resolution CT and Radioaerosol Scan Manifestations (미만성 범세기관지염에서 흉부 고해상도 전산화 단층촬영의 임상적의의 및 폐환기주사 소견)

  • Song, So Hyang;Kim, Hui Jung;Kim, Young Kyoon;Moon, Hwa Sik;Song, Jeong Sup;Park, Sung Hak;Kim, Hak Hee;Chung, Soo Kyo
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.1
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    • pp.124-135
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    • 1997
  • Background : Diffuse panbronchiolitis(DPB) is a disease characterized clinically by chronic cough, expectoration and dyspnea; and histologically by chronic inflammation localized mainly in the region of the respiratory bronchiole. It is prevalent in Japanese, but is known to be rare in Americans and Europians. Only a few cases in Chinese, Italians, North Americans and Koreans have been reported. It is diagnosed by characteristic clinical, radiological and pathologic features. High-resolution CT(HRCT) is known to be valuable in the study of the disease process and response to therapy in DPB. To our knowledge, there has been no correlation of its appearance on HRCT with the severity of the disease process, and radioaerosol scan(RAS) of the lung has not previously been used for the diagnosis of DPB. Method : During recent two years we have found 12 cases of DPB in Kangnam St. Mary's Hospital, Catholic University Medical College. We analysed the clinical characteristics, compared HRCT classifications with clinical stages of DPB, and determined characteristic RAS manifestations of DPB. Results : 1. The ages ranged from 31 to 83 years old(mean 54.5 years old), and male female ratio was 4:8. 75%(9/12) of patients had paranasal sinusitis, and only one patient was a smoker. 2. The patients were assigned to one of three clinical stages of DPB on the basis of clinical findings, sputum bacterology and arterial blood gas analysis. of 12 cases, 5 were in the first stage, 4 were in the second stage, and 3 were in the third stage. In most of the patients, pulmonary function tests showed marked obstructive and slight restrictive impairments. Sputum culture yielded P.aeruginosa in 3 cases of our 12 cases, K.pneumoniae in 2 cases, H.influenzae in 2 cases, and S.aureus in 2 cases. 3. Of 12 patients, none had stage I characteristics as classified on HRCT scans, 4 had slage II findings, 5 had stage III findings, and 3 had stage IV characteristics. 4. We peformed RAS in 7 of 12 patients With DPB. In 71.4% (5/7) of the patients, RAS showed mottled aerosol deposits characteristically in the transitional and intermediary airways with peripheral airspace defects, which contrasted sharply with central aerosol deposition of COPD. 5. There were significant correlations between HRCT stages and clinical stages(r= 0.614, P < 0.05), between HRCT types and Pa02(r= -0.614, P < 0.05), and between HRCT types and ESR(r= 0.618, P < 0.01). Conclusion : The HRCT classifications correspond well to the clinical stage. Therfore in the examination of patients with DPB, HRCT is useful in the evaluation of both the location and severity of the lesions. Also, RAS apears to be a convenient, noninvasive and useful diagnostic method of DPB.

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F-18 FDG PET Scan findings in Patients with Pulmonary Involvement in the Hypereosinophilic Syndrome (원발성 과호산구증가 증후군 환자들 중 폐침범을 보이는 환자군의 F-18 FDG PET 소견)

  • Lee, Jae-Hoon;Kim, Tae-Hoon;Yun, Mi-Jin;Hur, Jin;Kim, Tae-Sung;Kim, Sang-Jin;Kim, Hyung-Joong;Pai, Moon-Sun;Ryu, Young-Hoon;Lee, Jong-Doo
    • The Korean Journal of Nuclear Medicine
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    • v.39 no.4
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    • pp.239-245
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    • 2005
  • Purpose: Hypereosinophilic syndrome (HES) is an infiltrative disease of eosinophils affecting multiple organs including the iung. F-18 2-fluoro-2-deoxyglucose (F-18 FDG) may accumulate at sites of inflammation or injection, making interpretation of whole body PET scan difficult in patients with cancer. This study was to evaluate the PET findings of HES with lung involvement and to find out differential PET features between lung malignancy and HES with lung involvement. Material and Methods: F-18 FDG PET and low dose chest CT scan was performed for screening of lung cancer. light patients who showed ground-glass attenuation (GGA) and consolidation on chest CT scan with peripheral blood eosinophilia werr included in this study. The patients with history of parasite infection, allergy and collagen vascular disease were excluded. CT features and FDG PET findings were meticulously evaluated for the distribution of GGA and consolidation and nodules on CT scan and mean and maximal SUV of abnormalities depicted on F-18 FDG PET scan. In eight patients, follow-up chest CT scan and FDG PET scan were done one or two weeks after initial study. Results: F-18 FDG PET scan identified metabolically active lesions in seven out of eight patients. Maximal SUV was ranged from 2.8 to 10.6 and mean SUV was ranged from 2.2 to 7.2. Remaining one patient had maximal SUV of 1.3. On follow-up FDG PET scan taken on from one to four weeks later showed decreased degree of initially noted FDG uptakes or migration of previously noted abnormal FDG uptakes. Conclusions: Lung involvement in the HES might be identified as abnormal uptake foci on FDG PET scan mimicking lung cancer. Follow-up FDG PET and CT scan for the identification of migration or resolution of abnormalities and decrement of SUV would be of help for the differentiation between lung cancer and HES with lung involvement.

The Lung Expression of Proinflammatory Cytokines, TNF-$\alpha$ and Interleukin 6, in Early Periods of Endotoxemia (내독소혈증 유발 급성폐손상에서 폐장내 Proinflammatory Cytokines 발현에 관한 고찰)

  • Moon, Seung-Hyug;Kim, Yong-Hoon;Park, Choon-Sik;Lee, Shin-Je
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.3
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    • pp.553-564
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    • 1998
  • Background: The immediate hoot response to LPS is the production of proinflammatory cytokines that act as intercellular mediators in inflammatory reactions, including acute lung injury. These "early response" cytokines transmit signals from recognition cells to target or effector cells. This host response is further amplified by the expression of leukocyte chemoattractants, growth factors, and adhesion molecules, resulting in an array of proinflammatory events. This experiment was performed to define the lung origin of proinflammatory cytokines, such as TNF-$\alpha$, IL 6 in early periods of endotoxin induced acute lung injury (ALI). Method: The healthy male Sprague-Dawley, weighted 150 - 250g, were divided into saline control (NC) and endotoxemia-induced ALI (ETX-), and leukopenic endotoxemia-induced ALI (CPA-ETX-Group) which was induced by cyclophosphamide, 70 mg/kg i.p. injection. Acute lung injury was evoked by LPS, 5 mg/kg, intravenously administered. Bronchoalveolar lavage was performed at 0, 3, 6 h after LPS-treated to estimate the influx of phagocytes and concentration of total protein, and cytokines as TNF-$\alpha$ and IL 6 by a bioassy using MIT method. We also examined the localization of TNF-$\alpha$ and IL 6 protein in endotoxemia-challenged lung tissue by immunohistochemical stain (IH). Results: The total cell, macrophage and PMN count in BALF were elavated in ETX group compared to NC(p<0.05). In CPA-ETX group, total cell and macrophage count in BALF were not changed compared to NC. but PMN count was markedly reduced and it took part in less than 0.1 % of total BAL cells (p<0.01). The protein concentration in BALF were significantly increased in ETX and CPA-ETX group Compared to NC (p<0.05), but there was significant difference between ETX- and CPA-ETX group only at 6 h (p<0.05). This observation suggested that even if PMNs are involved in the pathogenesis of acute lung injury, their role cannot be viewed as essential The concentration of TNF-$\alpha$ and IL 6 in BALF was significantly increased in the ETX- and CPA-ETX group compared to NC. There was no difference between ETX- and CPA-ETX group. In IH, anti-TNF-$\alpha$- and anti-IL 6 antibody was strongly localized at interstitial monocytes and alveolar macrophages in endotoxemia-challenged lung tissue. From above point of view, activated alveolar macrophage/monocyte considered as a prominent source of proinflammatory cytokines in endotoxemia-challenged lung injury. Conclusion: The prominent source of proinflammatory cytokines in early periods of endotoxemia-induced lung injury will be the activated resident macrophages like an alveolar macrophage and interstitial monocytes. The pulmonary macrophage/monocyte will impact the initiation and continuance of lung injury without PMNs's certain inflammatory role, particularly in endotoxemia-induced acute lung injury.

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Multivessel Coronary Revascularization with Composite LITA-RA Y Graft (좌내흉동맥-요골동맥 복합이식편을 이용한 다중혈관 관상동맥우회술)

  • Lee Sub;Ko Mgo-Sung;Park Ki-Sung;Ryu Jae-Kean;Jang Jae-Suk;Kwon Oh-Choon
    • Journal of Chest Surgery
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    • v.39 no.5 s.262
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    • pp.359-365
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    • 2006
  • Background: Arterial grafts have been used to achieve better long-term results for coronary revascularization. Bilateral internal thoracic artery (ITA) grafts have a better results, but it may be not used in some situations such as diabetes and chronic obstructive pulmonary disease (COPD). We evaluated the clinical and angiographic results of composite left internal thoracic artery-radial artery (LITA-RA) Y graft. Material and Method: Between April 2002 and September 2004, 119 patients were enrolled in composite Y graft for coronary bypass surgery. The mean age was $62.6{\pm}8.8$ years old and female was 34.5%. Preoperative cardiac risk factors were as follows: hypertension 43.7%, diabetes 33.6%, smoker 41.2%, and hyperlipidemia 22.7%, There were emergency operation (14), cardiogenic shock (6), left ventricle ejection fraction (LVEF) less than 40% (17), and 17 cases of left main disease. Coronary angiography was done in 35 patients before the hospital discharge. Result: The number of distal anastomoses was $3.1{\pm}0.91$ and three patients (2.52%) died during hospital stay. The off-pump coronary artery bypass (OPCAB) was applied to 79 patients (66.4%). The LITA was anastomosed to left anterior descending system except three cases which was to lateral wall. The radial Y grafts were anastomosed to diagonal branches (4), ramus intermedius (21), obtuse marginal branches (109), posterolateral branches (12), and posterior descending coronary artery (8). Postoperative coronary angiography in 35 patients showed excellent patency rates (LITA 100%, and RA 88.5%; 3 RA grafts which anastomosed to coronary arteries <70% stenosed showed string sign with competitive flow). Conclusion: The LITA-RA Y composite graft provided good early clinical and angiographic results in multivessel coronary revascularization. But it should be cautiously used in selected patients.

The Comparative Study of on Pump CABG during Pulsatile $(T-PLS^{TM})$ and Nonpulsatile $(Bio-pump^{TM})$ Perfusion (관상동맥우회술 시 사용된 박동성펌프$(T-PLS^{TM})$와 비박동성펌프$(Bio-pump^{TM})$의 비교연구)

  • Park Young-Woo;Her Keun;Lim Jae-Ung;Shin Hwa-Kyun;Won Yong-Soon
    • 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 $T-PLS^{TM}$.

Airway Compression or Airway Anomaly Causing Respiratory Symptoms in Infants and Children with Cardiovascular Diseases (심혈관계 질환 환아에서 동반된 기도 압박 및 기도 기형의 임상적 특성)

  • Kim, Ja-Hyeong;Lee, So-Yeon;Kim, Hyo-Bin;Koo, So-Eun;Park, Sung-Jong;Kim, Young-Hui;Park, In-Suk;Ko, Jae-Gon;Seo, Dong-Man;Hong, Soo-Jong
    • Clinical and Experimental Pediatrics
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    • v.48 no.7
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    • pp.737-744
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    • 2005
  • Purpose : Infants and children with cardiovascular diseases often present with respiratory symptoms. However, missed or delayed evaluation for potential airway problem may complicate overall prognosis. The aim of this study is to determine the clinical characteristics of these patients and explore the cause of airway problem. Methods : We reviewed the medical records of 64 patients(M : F=33:31, mean age : $6.3{\pm}7.5$ months) whose airway problems were proven by computed tomography or bronchoscopy in perioperative periods at the Asan Medical Center from January 1997 to June 2004. Patients were divided into two groups based on the duration of ventilator care : ${\leq}7$ days(group 1 : 23 cases, M : F=10 : 13) and >7 days(group 2 : 41 cases, M : F=23 : 18). Results : The patients in group 2 significantly developed more post-operative respiratory symptoms than group 1(P<0.001) and had more airway problems including extrinsic obstruction, intrinsic anomaly, and combined problem than group 1 although not significantly different(P=0.082). Among underlying diseases, the most common diseases were vascular anomaly(26.2 percent) and aortic arch anomaly(26.2 percent) in group 1 and pulmonary atresia with ventricular septal defect(22.4 percent) in group 2. The most frequent respiratory symptoms were recurrent wheezing pre-operatively and failure of ventilator weaning post-operatively. The major types of airway anomaly were tracheomalacia and tracheal stenosis(in each case 18.2 percent). Nineteen patients with persistent airway problems underwent aortopexy or other vascular correction. Of the 19 patients, 13(68.4 percent) were improved, but 2 failed in weaning ventilator and 4 died of non-airway problems. Conclusion : Early evaluation and treatment for potential airway problems may affect natural or surgical prognosis in patients with cardiovascular diseases presenting with respiratory symptoms.

Effect of $H_2O_2$ on Alveolar Epithelial Barrier Properties (폐상피세포 장벽에 대한 $H_2O_2$의 영향)

  • Suh, Duk-Joon;Cho, Se-Heon;Kang, Chang-Woon
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.3
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    • pp.236-249
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    • 1993
  • Background: Among the injurious agents to which the lung airspaces are constantly exposed are reactive species of oxygen. It has been widely believed that reactive oxygen species may be implicated in the etiology of lung injuries. In order to elucidated how this oxidant causes lung cell injury, we investigated the effects of exogenous $H_2O_2$ on alveolar epithelial barrier characteristics. Methods: Rat type II alveolar epithelial cells were plated onto tissue culture-treated polycarbonate membrane filters. The resulting confluent monolayers on days 3 and 4 were mounted in a modified Ussing chamber and bathed on both sides with HEPES-buffered Ringer solution. The changes in short-circuit current (Isc) and monolayer resistance (R) in response to the exogenous hydroperoxide were measured. To determine the degree of cellular catalase participation in protection against $H_2O_2$ injury to the barrier, experiments were repeated in the presence of 20 mM aminotriazole (ATAZ, an inhibitor of catalase) in the same bathing fluid as the hydroperoxide. Results: These monolayers have a high transepithelial resistance (>2000 ohm-$cm^2$) and actively transport $Na^+$ from apical fluid. $H_2O_2$(0-100 mM) was then delivered to either apical or basolateral fluid. Resulting indicated that $H_2O_2$ decreased Isc and R gradually in dose-dependent manner. The effective concentration of apical $H_2O_2$ at which Isc (or R) was decreased by 50% at one hour ($ED_{50}$) was about 4 mM. However, basolateral $H_2O_2$ exposure led to $ED_{50}$ for Isc (and R) of about 0.04 mM. Inhibition of cellular catalase yielded $ED_{50}$ for Isc (and R) of about 0.4 mM when $H_2O_2$ was given apically, while $ED_{50}$ for basolateral exposure to $H_2O_2$ did not change in the presence of ATAZ. The rate of $H_2O_2$ consumption in apical and basolateral bathing fluids was the same, while cellualr catalase activity rose gradually with time in culture. Conclusion: Our data suggest that basolateral $H_2O_2$ may affect directly membrane component (e.g., $Na^+,\;K^+$-ATPase) located on the basolateral cell surface. Apical $H_2O_2$, on the other hand, may be largely degraded by catalase as it passes through the cells before reaching these membrane components. We conclude that alveolar epithelial barrier integrity as measured by Isc and R are compromised by $H_2O_2$ being relatively sensitive to basolateral (and insensitive to apical) $H_2O_2$.

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