• Journal of Life Science
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• v.17 no.4 s.84
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• pp.515-521
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• 2007

Aprotinin, a serine protease inhibitor, has been used to ameliorate the inevitable consequences, including blood component injury after cardiac surgery with cardiopulmonary bypass (CPB). However, there are many arguments on its dosage or usage. We assessed whether administration of low dose of aprotinin in only priming solution has any beneficial effect or reduces its side effects on cardiac surgery. Thirty patients scheduled for elective cardiac surgery were randomly assigned to aprotinin group (n=15) which received aprotinin in priming solution (two million kallikrein inhibitory unit, KIU) and added one million KIU at 1 hour after the beginning of CPB or control group (n=15) which did not receive it. Hematological and biochemical variables, cytokines and cardiac marker levels, and postoperative outcomes were compared between two groups at before, during or after operation. Platelet count in aprotinin group was higher than that of control group at postoperative 24 hr. Activated partial thromboplastin time in aprotinin group was longer than that of control group at intensive care unit (ICU). Troponin-I level and postoperative blood loss volumes in aprotinin group were lower than those of control group at ICU. There were no significant differences between the two groups on the others. These results showed that low dosage of only priming solution during cardiac surgery with CPB reduced platelet destruction and postoperative bleeding, and attenuates myocardial damage. However, further studies need to be carried out with more population or pediatric patients for evaluating various aprotinin usage.

• Journal of Chest Surgery
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• v.13 no.1
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• pp.13-20
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• 1980

Heparin would have been used for preventing clotting of blood during extracorporeal circulation and subsequent use of protamine sulfate and made possible the neutralization of heparin. This procedure has been adopted for eliminating one of the great causes of bleeding, especially in cardiac surgery. In this experiment, the hypocoagulability of blood induced by heparin followed by neutralization with treatment of protamine sulfate were estimated by the Lee-White clotting time [CT], partial thromboplastin time [PTT] and protamine titration test. The results were as follows: 1] Comparison of clotting time between the heparinized [2.0 mg/kg] and non-heparinized dogs was done using CT and PT`I` of the blood. In heparinized group [Group I], the CT lasted infinitively and prolongation of PTT [4 times than normal] until 60 minutes. The CT [2 times] and PTT [3 times] has been shortened after 90 minutes, however they returned to normal limit level within 180 minutes. 2] The determination of appropriate ratio of heparin and protamine In vivo were performed. The group II [heparin 2.0 mg/kg, protamine 1.0 mg/kg] revealed rapid decrease of CT and PTT, but returned to normal after 120 minutes. The group III [heparin 2.0 mg/kg, protamine 2.0 mg/kg] returned rapidly to normal within 15 minutes. The group IV [heparin 2.0 mg/kg, protamine 3.0 mg/kg] recovered its normal level after 60 minutes. The group V [heparin 2.0 mg/kg, protamine 4.0 mg/kg] recovered its normal level after 90 minutes. 3] In the combined experimental study In vivo and vitro, the protamine titration test was done using the dog which were given 2.0 mg/kg and 3.0 mg/kg of heparin, respectively and coagulation time were checked after 15, 30, 60 and 120 minutes. The complete neutralization was showed to be heparin-protamine ratio of 1:1 to 1.5. 4] In vitro study, fresh blood was drawn into known amount of heparin content [20, 40, 60 and 100/ug per 1 ml of blood] syringe, thereafter protamine titration test was done. In all cases, the complete neutralization was found in heparin-protamine ratio of 1:0.85 to 1.5. 5] It was found by the present experiment that the ideal heparin-protamine ratio was 1:1 within 60 minutes and 1:0.5 after 60 minutes for avoiding the serious side effect due to overadministration of protamine sulfate.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.3
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• pp.229-234
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• 2015

Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and anti-inflammatory effects. NM has been used in Asia for anticoagulation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Oxidative stress is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial function. We investigated whether NM could inhibit endothelial dysfunction induced by tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$ ). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-${\alpha}$ for 24 h. The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogenactivated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM ($0.01{\sim}100{\mu}g/mL$) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF-${\alpha}$ (3 ng/mL), and it dose dependently prevented the TNF-${\alpha}$ -induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF-${\alpha}$ -induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF-${\alpha}$ -induced monocyte adhesion and the expression of endothelial cell adhesion molecules, and that the anti-adhesive effect of NM is mediated through the inhibition of p66shc, ROS production, and p38 MAPK activation.

• Journal of Chest Surgery
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• v.31 no.5
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• pp.481-487
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• 1998

The surgical management of acute type B dissection is controversial. The complexity of the repair usually requires a period of aortic cross-clamping exceeding 30 minutes, which can cause ischemic injury of the spinal cord. Several forms of distal perfusion have been considered for use to prevent this injury. To determine the safety and efficacy of a graft replacement with cardiopulmonary bypass in reparing acute dissection of descending thoracic aorta, we retrospectively reviewed our surgical experience treating 8 patients who had aortic dissection secondary to atherosclerosis, trauma, and carcinoma invasion. Cardiopulmonary bypass was performed with two aortic cannulas for simultaneous perfusion of the upper and lower body and one venous cannula for draining venous blood from the right atrium or inferior vena cava. Although aortic cross-clamp time was relatively long (average, 117.8 minutes; range, 47 to 180 minutes) in all cases, there was no neurologic deficit immediately after graft replacement for the aortic lesion. Two patients(25%) of relatively old age died on the postoperative 31st and 41st days, respectively, because of delayed postoperative complications, such as pulmonary abscess and adult respiratory distress syndrome. Although any of several maneuvers may be appropriate in managing dissection of the descending aorta, graft replacement with cardiopulmonary bypass during aortic cross-clamping may be a safe and effective method for the treatment of acute dissection of the descending thoracic aorta.

• Journal of Biomedical Engineering Research
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• v.40 no.5
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• pp.197-205
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• 2019

The existing Extracorporeal membrane oxygenation(ECMO) and Cardiopulmonary bypass system(CPB) have been developed and applied to various devices according to their respective indications. However, due to the complicated configuration and difficult usage method, it causes inconvenience to users and there is a risk of an accident. Therefore, smart all-in-one cardiopulmonary circulation device is being developed recently. The smart all-in-one cardiopulmonary assist device consists of a blood pump for cardiopulmonary bypass, a blood oxidizer for cardiopulmonary bypass, a blood circuit for cardiopulmonary bypass, and an artificial cardiopulmonary device. It is an integrated cardiopulmonary bypass device that can be used for a variety of purposes such as emergency, intraoperative, post-operative intensive care, and long-term cardiopulmonary assist, combined with CPB used in open heart surgery and ECMO used when patient's cardiopulmonary function does not work normally. The smart all-in-one cardiopulmonary assist device does not exist as a standard and international standard applicable to advanced medical devices. Therefore, in this study, we will refer to the International Standard for Blood Components, the International Standard for Blood, the Guideline for Blood Products, and prepare applicable performance and safety guidelines to help quality control of medical devices, and contribute to the improvement of the health of people. The guideline, which is the result of conducted a survey of the method of safety and performance test, is based on the principle of all-in-one cardiopulmonary aiding device, related domestic foreign standards, the status of domestic and foreign patents, related literature, blood pump(ISO 18242), blood oxygenator (ISO 7199), and blood circuit (ISO 15676) for cardiopulmonary bypass.The items on blood safety are as follows: American Society for Testing and Materials ASTM F1841-97R17), and in the 2010 Food and Drug Administration's Safety Assessment Guidelines for Medical Assisted Circulatory Devices. In addition, after reviewing the guidelines drawn up through expert consultation bodies including manufacturers / importers, testing inspectors, academia, etc. the final guideline was established through revision and supplementation process. Therefore, we propose guidelines for evaluating the safety and performance of smart all-in-one cardiopulmonary assist devices in line with growing technology.

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

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

• Journal of Chest Surgery
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• v.9 no.1
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• pp.1-9
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• 1976

The present. study reports four cases of congenital heart diseases, who received open heart surgery by the Sarn's Heart-Lung-Machine in the department of Thoracic Surgery, Hanyang University Hospital during the period between July 1975 and May 1976. The Heart-Lung-Machine consisted of the Sarn's five head roller pump motor system (model 5000), heat exchanger, bubble trap, the Rygg-Kyvsgaard oxygenator, and monitors. The priming of pump oxygenator was carried out by the hemodilution method using Hartman's solution and whole blood. Of the four cases of the heart diseases, three whose body weight were below 30kg, received the partial hemodilution priming and the remaining one whose body weight was 52kg received the total hemodilution priming with Hartman's solution alone. The rate of hemodilution was in the average of 60.5ml/kg. Extracorporeal circulation was performed at the perfusion flow rate of the average 94.0ml/kg/min, and at the moderate hypothermia between 35'5"C and 30'5"C of the rectal temperature. In the total cardiopulmonary bypass, arterial blood pressure was anged between 30 mmHg and 85 mmHg, generally maintaining over 60 mmHg and venous pressure was measured between 4 and $23cmH_2O$, generally maintaining below $10cmH_2O$. The first case: The patient, a nine year old girl having the symptoms and physical signs typical to cardiac anomaly was definitely diagnosed as isolated pulmonary stenosis through the cardiac catheterization. There was, however, no cyanosis, no pathological finding by X-ray and E.C.G. tracings. The valvulotomy was performed through the arteriotomy of pulmouary artery under the total cardiopulmonary bypass. Postoperative course of the patient was uneventful, and murmur and the clinical symptoms disappeared. The second case: A 12 year old boy with congenital heart anomaly was positively identified as having ventricular septal defect through the cardiac catheterization. As in the case with the first case, the patient exhibited the symptoms and physical signs typical to cardiac anomaly, but no pathological abnormality by X-ray and E.C.G. tracings. The septal defect was localized on atrioventricular canal and was 2 by 10 mm in size. The septal defect was closed by direct simple sutures under the cardiopulmonary bypass. Postoperative hemodynamic study revealed that the pressure of the right ventricle and pulmonary artery were decreased satisfactory. Postoperative course of the patient was uneventful, and murmur and the clinical symptoms disappeared. The third case: The patient, a 19 year old girl had been experienced the clinical symptoms typical to cardiac anomaly for 16 years. The pink tetralogy of Fallot was definitey diagnosed through the cardiac catheterization. The patient was placed on an ablolute bed rest prior to the operation because of severe exertional dyspnea, fatigability, and frequent syncopal attacks. However, she exhibited very slight cyanosis. Positive findings were noted on E.C.G. tracings and blood picture, but no evidence of pathological abnormality on X-ray was observed. All of the four surgical approaches such as Teflon patch closure (3 by 4cm in size) of ventricular septal defect, myocardial resection of right ventricular outflow tract, valvulotomy of pulmonary valvular stenosis, and pericardial patch closing of ventriculotomy wound were performed in 95 minutes under the cardiopulmonary bypass. Postoperative hemodynamic study revealed that the pressure of the right ventricle was decreased and pulmonary artery was increased satisfactorily. Postoperative course of the patient was uneventful, and murmur and the clinical symptoms disappeared. The fourth case: The patient, a 7 1/4 year old girl had the symptoms of cardiac anomaly for only three years prior to the operation. She was positively identified as having acyanotic tetralogy of Fallot by open heart surgery. The patient showed positive findings by X-ray and E.C.G. tracings, but exhibited no cyanosis and normal blood picture. All of the three surgical approaches, such a myocardial resection of hypertrophic sight ventricular outflow tract, direct suture closing of ventricular septal defect and pericardial patch closing of ventriculotomy wound were carried out in 110 minutes under the cardiopulmonary bypass. Postoperative hemodynamic study revealed that the pressure of the right ventricle was decreased and pulmonary artery was increased satisfactorily. Postoperative course of the patient was uneventful, and the symptoms disappeared.

• Journal of Chest Surgery
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• v.31 no.11
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• pp.1043-1048
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• 1998

Background: As coronary arterial disease is increasing, we evaluated the patients who underwent CABG(Coronary Artery Bypass Grafting) and thus report the early results and risk factors related to mortality and morbidity. Materials and methods: Between July 1996 and February 1998, 42 patients underwent CABG. We analyzed age, sex, preoperative ejection fraction, Canadian heart classification, prevalence factors of CAD(Coronary Artery Disease), angiographic findings, graft vessel numbers, IMA(Internal Mallary Artery) use, ECC* (extracorporeal circulation) time and morbidity. We also evaluated the mortality rate and the causes of death. Results: Complication was developed at 17cases. The average age of the complication group was 61±11.9 years and that of the noncomplication group was 51±10.5 years(p=0.004). ECC time was 198±42.5(min) in the complication group and 158±47.4(min) in the noncomplication group(p=0.008). The other factors had no correlation to the morbidity, statistically. The average follow up duration was 12.5 months and all the patients were alive except for the 2 expired cases. The mortality rate was 4.7%, among which one patient who underwent CABG with aortic valve replacement died due to multiorgan failure and the other died due to sepsis with pneumonia and wound infection. Conclusions: We conclude that the risk factors related to morbidity were age and ECC time, and that there were no correlations between other factors and morbidity.

• Journal of Chest Surgery
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• v.29 no.7
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• pp.700-712
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• 1996

Transpulmonary sequestration of leukocyte following cardiopulmonary bypass(CPB) has been recognized as one of main causes of postoperative pulmonary dysfunction. The purpose of this study is to investigate the effect of a single dose of prebypass corticosteroid on pulmonary leukostasis and postoperative pulmonary dysfunction. The study was performed prospectively in randomized-blind fas ion for 50 patients from January 1995 to June 1995. All patients were divided into two groups; In the steroid group(n=25), corticosteroid(Solu-Medrol 30mg1kg) was injected prior to CPB and in the placebo group (n=25), normal saline was injected before CPB. The results were summarized as follows. 1. Total peripheral leukocyte counts decreased significantly at 5 minutes of CPB in all patients(P<0.01), and began to increase progressively at later periods of CPB with neutrophilia. The significant rise remained at postoperative 7th day. 2. During partial CPB, transpulmonary leukostasis occurred in placebo group(P< 0.001), whereas it was prevented in steroid group. 3. In both groups, peripheral Lymphocyte counts were stable during CPB, but began to reduce at time of intensive care unit(ICV) and the Iymphocytopenia remained until postoperative )rd day. The Iympho- cyte counts recovered on postoperative 7th day. 4. In both groups, peripheral counts of monocyte were relatively stable in the e rly peroid of CPB, and increased gradually in the later periods of CPB. This significant monocytosis remained throughout postoperative periods(P< 0.05). 5. The mean value of postoperative PaOa was lower than that of pre-CPB In placebo group(P=0.01), but in steroid group, there was no significant difference(P=0. 90) and fever was higher in placebo group compared to steroid group(P=0.001).

• Journal of Chest Surgery
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• v.32 no.6
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• pp.495-503
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• 1999

Background: We tested the technical feasibility of fetal cardiac bypass and collected baseline data on the fetal hemodynamics and placental functions related to the cardiopulmonary bypass in the fetal lamb model. Material and Method: Eleven fetuses at 120 to 150 days of gestation were subjected to bypass via trans-sternal approach with a 12 G pulmonary arterial cannula and 14 to 18 F venous cannula for 30 minutes. All ewes received general anesthesia with ketamine. In all the fetuses, no anesthetic agents were used except muscle relaxant. Eight served as a group in which placenta was excluded from the extracorporeal circulation by clamping the umbilical cord during the bypass(the oxygenator group) and in the remaining three, the placenta worked as the only source of oxygen supply(the placenta group). Observations were made every 10 minute during a 30-minute bypass and 30-minute post bypass period. No prostaglandin inhibitors were used both in ewes and in fetuses. Result: Weights of the fetuses ranged from 1.9 to 5.2 kg. In the oxygenator group, means of arterial pressure, PaO2, atrial pressure, heart rate, and bypass flow rate ranged 69.8 to 82.6 mmHg, 201.7 to 220.9 mmHg, 4.1 to 4.3 mmHg, 169 to 182/min, and 140.3 to 164.0 ml/kg/min, respectively during bypass, but rapid deterioration of the fetal cardiac functions and the placental gas exchange was observed after the cessation of bypass. In the placenta group, means of arterial pressure decreased from 44.7 to 14.4 mmHg and means of PaCO2 increased from 61.9 to 129.6 mmHg during bypass. Flow rate was suboptimal(74.3 to 97.0 ml/kg/min) during bypass. All hearts fibrillated immediately after the discontinuation of bypass. Conclusion: In this study, the technical feasibility of fetal cardiopulmonary bypass was confirmed in the fetal lamb model. However, further studies with modifications of the bypass including an addition of prostaglandin inhibitor, an application of the total spinal anesthesia on the fetus, a creation of more concise bypass circuit, and a use of active pump are mandatory to improve the outcome.