• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.213-223
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• 1993

To investigate the endothelium dependent vascular reactivity of the systemic arterial and the pulmonary arterial system in acute renal hypertensive rats of 2-kidney, 1-ligation type (RHRs), acetylcholine (ACh)-induced vasodilation and depressor effects were evaluated in isolated arteries and in vivo, respectively, in the presence and absence of functional endothelium. ACh $(10^{-5}\;M)$ relaxed the intact thoracic aortas from RHRs and normotensive rats (NRs), but the effect was significantly smaller for those from RHRs (34 and 86%, respectively, p<0.01). ACh-induced vasodilation was completely abolished after removal of endothelial cell or pretreatment with EDRF inhibitors, L-NAME and MB, indicative of its dependence on intact endothelial or EDRF function. ACh also induced vasorelaxation of the intact pulmonary arteries from RHRs and NRs; however, unlike the effects on the thorcic aorta, no significant difference in amplitude was noted between two groups. ACh $(0.1{\sim}10\;{\mu}g/kg,\;i.v.)$ reduced mean systemic arterial pressure in anesthetized RHRs and in NRs to the similar magnitude (% change: 39 and 46% at $10\;{\mu}g/kg$, respectively) and these hypotensive effects were significantly decreased after pretreatment with L-NAME (30 mg/kg, i.v.). Deprssor effects of ACh on mean pulmonary arterial pressure were similar in RHRs and NRs with and without pretreatment of L-NAME. However, in both NRs and RHRs, the depressor effects of ACh on mean pulmonary arterial pressure were significantly reduced compared with those for mean systemic arterial pressure, and the increment of mean pulmonary arterial pressure noted after L-NAME $(0.1{\mu}100\;mg/kg,\;i.v.)$ was significantly smaller than that for mean systemic arterial pressure. These results indicate that in RHRs the endothelial cell function was impaired, at least in part, in systemic arterial system, but not in pulmonary arterial system, and both ACh-evoked and basal release of EDRF was less in the pulmonary arterial system than in systemic arterial system of both NRs and RHRs.

• Journal of Chest Surgery
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• v.35 no.7
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• pp.511-516
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• 2002

Background: This study was undertaken in infant patients with isolated ventricular septal defect(VSD) to determine the effect of surgical closure on ventricular systolic time interval, as a parameter for ventricular performance, by echocardiography. Material and Method: Thirty patients were enrolled. Mean age of patients at operation was 6.5$\pm$3.2 months and all patients had non-restrictive VSD. We checked the left atrium/aorta(LA/Ao) ratio, left ventricle ejection fraction(EF), left ventricular systolic time interval(LVSTI), and right ventricular systolic time interval(RVSTI). Echocardiographic studies were done before surgical correction and postoperative periods(postopl: within 2 weeks, postop2: between 4 and 6 months, postop3: between 1 and 2 years). Result: LA/Ao ratio decreased significantly at immediate postoperative period compared to preoperative period and sustained during further follow-up period(from 1.74$\pm$0.37 to 1.36$\pm$0.24＊, 1.32$\pm$0.22＊, and 1.27$\pm$0.19＊, p<0.01). LV EF had not changed during follow-up periods(from 65.1$\pm$7.0 to 62.3$\pm$9.5, 62.8$\pm$5.7, and 64.1$\pm$6.9). LVSTI decreased significantly at postop2 and sustained during further follow-up period (from 0.46$\pm$0.13 to 0.46$\pm$0.11, 0.37$\pm$0.08＊, and 0.34$\pm$0.07＊, p<0.01). RVSTI decreased significantly at postop3(0.33$\pm$0.08 to 0.32$\pm$0.08, 0.31$\pm$0.07, and 0.27$\pm$0.05＊, p<0.01). Conclusion: We found that right and left ventricular systolic time intervals had decreased over the period of 1 year after surgical correction of VSD. Therefore, it is necessary to observe the change of ventricular function during that period.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.45-52
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• 1991

The inhibitory effects of GS354 and GS389 on cytosolic $Ca^{2+}$ level ($[Ca^{2+}]_{1}$; measured with fura-2 fluorescence) and muscle tension in vascular smooth muscle of rat thoracic aorta were investigated. Both GS354 and GS389 inhibited the contractions induced by high $K^+$ or by norepinephrine. The vasodilator effect of GS354 was accompanied by a decrease in $[Ca^{2+}]_{1}$. The inhibitory effect on high $K^+-stimulated$ $[Ca^{2+}]_{1}$ was antagonized by a $Ca^{2+}$ channel activator, Bay K8644. However, the inhibitory effect on muscle tension was not antagonized by Bay K8644. These results suggest that GS354 inhibits $Ca^{2+}$ channels to decrease $[Ca^{2+}]_{1}$ and also decreases $Ca^{2+}$ sensitivity of contractile elements. The inhibitory effects of GS389 was accompanied by the increase in tissue fluorescence. This increment was not due to fura-2 fluorescence but to endogeneous pyridine nucleotides, suggesting that GS389 has an effect to inhibit mitochondrial function. Because of this interference, effects of GS389 on $[Ca^{2+}]_{1}$ was obscured. However, since sequential addition of Bay K8644 in the presence of GS389 further increased the fluorescence but not muscle tension, this compound seems to have the effects to inhibit $Ca^{2+}$ channels and to decrease $Ca^{2+}$ sensitivity of contractile elements.

• Journal of Chest Surgery
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• v.36 no.8
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• pp.566-575
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• 2003

We reviewed our 18-year surgical experience of biventricular repair for double-outlet right ventricle. Material and Method: One hundred twelve consecutive patients (80 males and 32 females) who underwent biventricular repair for double-outlet right ventricle between May 1986 and September 2002 were included. We assessed risk factors for early mortality and reoperation. Reoperation-free survival rate and actual survival rate were analysed. Result: Most common type of ventricular septal defect was subaortic (n=58, 52%) and non-committed type was second most common (n=32, 29%). Four different surgical methods were used: intraventricular baffle repair (n=71 , 63%): right ventricle to pulmonary ariery conduit interposition or REV with left ventricle to aorta baffle repair (n=24, 21 .4%): arierial switch operation with left ventricle to pulmonary artery baffle (n=14, 12.5%): Senning atrial switch operation with left ventricle to pulmonary artery baffle (n=3, 2.7%). Thirty four patients(30%) underwent palliative procedures before definite repair. Twenty three patients (21%) required reoperations. There were 12 (10.7%) early deaths and 4 late deaths. Age younger than 3 months at repair (p=0.003), cardiopulmonary bypass and aortic cross clamp time (p=0.015, p=0.067), type of operation (arterial switch operation) (p <0.001) and type of ventricular septal defect (subpulmonic type) (p=0.002) were revealed as risk factors for early death in univariate analysis, while age under 3 months was the only significant risk factor in multivariate analysis. Patients younger than 1 year of age (p=0.02), pulmonary artery angioplasty at definitive repair (p=0.024), type of ventricular septal defect (non-committed) (p=0.001), type of operation (right ventricle to pulmonary artery conduit interposition and REV operation) (p=0.028, p=0.017) were risk factors for reoperation in univariate analysis but there was no significant risk factor in multivariate analysis. Follow-up was available on 91 survivals with a mean duration of 110.8$\pm$56.4 (2~201) months. 5, 10 and 15 year survival rates were 86.5%, 85% and 85% and reoperation free survival were 85%, 71.5%, 70%. Conclusion: Age under 3 months at repair, subpulmonic ventricular septal defect and arterial switch operation were significant risk factors for early mortality. Patients with non-committed ventricular septal defect and who underwent conduit interposition or REV operation were risk factors for reoperation. With careful attention to chose best timing and surgical approach depending on morphologic characteristics, biventricular repair for double outlet right ventricle can be achieved with good long-term outcome.

• Tuberculosis and Respiratory Diseases
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• v.41 no.6
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• pp.616-623
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• 1994

Objectives: Careful evaluation about mediastinal involvement is important in the management of patients with non-small cell lung cancer. Invasive staging procedure such as mediastinoscopy is advocated because of the unreliability of noninvasive staging methods such as CT, MRI. We compared differences between pre- and postoperative staging in non-small cell lung cancer without lymphadenopathy on CT scan and investigated the methods for more accurate preoperative staging. Methods & Results: 1) Records of a total of 41 patients with preoperative $T_{1-3}N_0M_0$ non-small cell lung cancer were reviewed and the histologic types of tumors were squamous cell carcinoma in 32 cases, adenocarcinoma in 6 cases and large cell carcinoma in 3 cases. Twenty-four cases were central lesions and seventeen cases were peripheral lesions. 2) Among the 32 cases with preoperative $T_2$, 2 cases were identified postoperatively as $T_3$ with invasion of chest wall and among 6 cases with preoperative $T_3$, 1 case was identified postoperatively as $T_4$ with invasion of aorta and pulmonary arteries. 3) After the operation of 35 cases with $T_{1-2}$, 5 cases were $N_1$ and 3 cases were $N_2$ postoperatively. After the operation of 6 cases with $T_3$, 2 cases were $N_1$ and 3 cases were $N_2$ postoperatively. Preoperative $T_3$ showed more intrathoracic lymph node metastases and higher $N_2/N_1$ involvement ratio than preoperative $T_{1-2}$. 4) Complete surgical resections were done in 34 out of 41 cases. Incomplete resection were done in all postoperative $N_2$ tumors. Conclusion: Invasive staging procedures such as mediastinoscopy should be considered in the case of preoperative $T_3$ non-small cell lung cancer even though mediastinal lymphadenopathy is not recognized on the CT scan of the chest.

• Journal of Chest Surgery
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• v.31 no.5
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• pp.466-471
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• 1998

Purpose: The safety and efficacy of minimally invasive techniques in congenital heart surgery were tested in this study. Materal and method: Between July 1997 and November 1997, a total of 46 children were underwent minimally invasive cardiac operations at Seoul National University Children's Hospital. Age and body weight of the patients averaged 34.6${\pm}$41.8 (Range: 1∼148) months and 14.5${\pm}$9.9(Range: 3.0∼40.0) kg, respectively. Twenty eight patients were male. Preoperative surgical indications included 15 atrial septal defects, 25 ventricular septal defects, 1 foreign body in aorta, 3 partial atrioventricular septal defects, 1 total anomalous pulmonary venous connection(cardiac type), and 1 tetralogy of Fallot. After creating a small lower midline skin incision starting as down as possible from the sternal notch, a vertical midline sternotomy extended from xyphoid process to the level of the second intercostal space, where one of the T-, J-, I- or inverted C-shaped lower lying mini-sternotomy was completed with a creation of unilateral right or bilateral trap door sternal opening. A conventional direct aortic and bicaval cannulation was routine. Result: A mean length of skin incision was 6.1${\pm}$1.0(range: 4.0∼9.0) cm. A mean distance between the suprasternal notch and the upper most point of the skin incision was 4.0${\pm}$1.1 (range: 2.0∼7.0) cm. Mean cardiopulmonary bypass time, aortic cross-clamp time, and the operation time were 62.9${\pm}$20.0(range: 28∼147), 29.8${\pm}$12.8(range: 11∼79), and 161.1${\pm}$34.5 (range: 100-250) minutes. A mean total amount of postoperative blood transfusion was 71.0${\pm}$68.1 (range: 0∼267) cc. All patients were extubated mean 11.3${\pm}$13.8(range: 1∼73) hours after operation. A mean total amount of analgesics used was 0.8${\pm}$1.8(range: 0∼9) mg of morphine. The mean duration of stay in intensive care unit and hospital stay were 35.0${\pm}$32.2 (range: 10∼194) hours and 6.2${\pm}$2.0(range: 3∼11) days. There were no wound complications and hospital deaths. Conclusion: This short-term experience disclosed that the minimally invasive technique can be feasibly applied in a selected group of congenital heart disease as well as is cosmetically more attractive approach.

• Journal of Chest Surgery
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• v.37 no.5
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• pp.391-400
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• 2004

Xenotransplantation in discordant species results in immediate and irreversible hyperacute rejection due to natural antibodies, IgM. With this, antibody depletion is one option to reduce hyperacute rejection, we investigated the effect of PCPP (postcentrifugal plasmapheresis) on the depletion of natural antibodies and the effect of antibody titer on xenograft survival. Material and Method: Outbred swines (n=4) weighing 10∼20 kg were used as donors and mongrel dogs (n=4) weighing 25∼30 kg were used as recipients. Recipient canines underwent plasmapheresis (COBE TPE Laboratories, Lakewood. CO, USA). Pre-transplantation PCPP was peformed on day －2 and day 0. There were three groups (Group 0: no PCPP, Group 1: 1 pla sma-volume (PV) at day －2 and 2 PV at day 0, Group 2: 2 PV at day －2 and 2 PV at day 0). A swine heart was heterotopically transplanted into a recipient's abdominal infrarenal aorta and inferior vena cava. Mean percent depletion of total IgM and IgG in plasma of the recipients was calculated. Serum albumin, electrolyte, complement activity and coagulation factors were measured. Histopathologic examination of heart specimens was performed. Result: Mean percent depletion of IgM and IgG were 95.7$\pm$1.2%, 80.5$\pm$2.4% in the group 2 at the end of PCPP. The percent depletion of serum albumin concentration was decreased from 2.8 to 1.4 g/㎗ in the group 1 and 3.0 to 1.5 g/㎗ in the group 2. Complement hemolytic activity was decreased in group 1 and 2, but returned to normal level within 24 hours. Complement hemolytic activity was reduced to 10% of pre-PCPP level in group 2. Serum fibrinogen decreased to 20% or less and was recovered within 24 hours in group 2. Antithrombin III decreased but less than fibrinogen. PT and aPTT were sometimes but not always prolonged during plasmapheresis. After plasmapheresis, PT and aPTT were prolonged beyond the measurable level. D-dimer was not found during PCPP, but appeared and maintained from 10 minutes after trasplantation. Graft Survival time was 5 min in group 0, and it was 90$\pm$0 min in the group 2. Histopathologic changes were more typically characterized by edema, hemorrhages, thrombosis in all groups at the end of experiment. Conclusion: PCPP effectively removed immuoglobulins and reduced the titer of natural antibodies, as a result, significantly prololonged swine heart xenograft survival.

• Journal of Chest Surgery
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• v.35 no.6
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• pp.430-438
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• 2002

It is known that low birth weight is a risk factor for poor outcome in cardiac surgery for many cardiac defects. We reviewed our recent surgical experiences on congenital heart defect (other than patent ductus arteriosus) in low birth weight babies. Material and Method: From September 1994 to February 2001, 31 consecutive infants weighing 2500 g or less underwent cardiac surgery with (OHS group n=12) or without cardiopulmonary bypass (CHS group n=19). A retrospective study was carried out to evaluate short-and intermediate-term outcome. Mean gestational age and age at operation were 36.9 weeks(range, 32.3-42weeks) and 32.1days (range, 0-87days) respectively. Mean body weight at birth and operation were 1972g (range, 1100-2500g) and 2105g (range, 1450-2500 g) respectively. There was no difference between the two groups in age and body weight. Defects included ventricular septal defect (VSD) (n=3), VSD with arch anomaly (n=2), total anomalous pulmonary venous return (n=2), transposition of the great arteries (TGA) (n=2), truncus arteriosus (n=2), and univentricular heart with cor triatriatum (n=1) in OHS group, and coarctation of aorta (n=7), tetralogy of Fallot (TOF) (n=3), TOF with pulmonary atresia (n=3), multiple muscular VSDs (n=1), double outlet right ventricle (n=1), pulmonary atresia with intact ventricular septum (n=2), tricuspid atresia (n=1), and TGA with multiple VSD (n=1) in CHS group. 13 patients (41.9%) were intubated pre-operatively. Result: There were 4 early deaths(＜30 days); 1 (8.3%) in OHS group and 3 (15.8%) in non-OHS group. All these early deaths were related to the pulmonary artery banding(PAB). There was no operative mortality in infants undergoing complete repair and palliative operations other than PAB. Delayed sternal closure was required in 3 patients. Prolonged postoperative mechanical ventilation (>7 days) was required in 7 patients(58.3%) in OHS and 7(38.8%) in CHS group. Late mortality occurred in 3 patients, two of which were non-cardiac. A patient in OHS group was documented to have neurologic sequelae. All the survivors except two are in NYHA class 1. Conclusion: Complete repair and palliative operations other than PAB can be performed in low birth weight infants with low operative mortality and an acceptable intermediate-term result. However, about a half of the patients required long-term postoperative mechanical ventilation.

• 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.