• Journal of Chest Surgery
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• v.20 no.4
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• pp.643-654
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• 1987

The effect of prostacyclin[PGI, ] on myocardial preservation during global ischemia was studied in the isolating working rabbit heart model. Forty hearts underwent a 15 minute period of retrograde nonworking perfusion with Krebs-Henseleit buffer solution [37*C] and were switched over to the working mode for 15 minutes. After baseline measurement of heart rate, peak aortic pressure, aortic flow, and coronary flow, all hearts were subjected to 60 minutes of ischemic arrest at 10*C induced with St. Thomas Hospital cardioplegic solution: Group I had single dose cardioplegia, Croup II double dose, Croup III oxygenated double dose, and Group IV single dose with PCI, infusion [10ng/min./gm heart weight]. Hearts were then revived with 15 minute period of nonworking reperfusion at normothermia, followed by 30 minutes of working perfusion. Repeat measurements of cardiac function were obtained and expressed as a percent of the preischemic baseline values. Oxygen content of arterial perfusate and coronary effluent was measured by designed time interval. Leakage of creatine kinase was determined during post-ischemic reperfusion period. Finally wet hearts were weighed and placed in 120*C oven for 36 hours for measurement of dry weight. In the PGI, treated group [IV], heart rate increased consistently throughout the period of reperfusion from 100*5.0% [p<0.001] to 107*6.2% [p<0.001]. The percent recovery of aortic flow showed 95*5.7% [p<0.001] at the first 3 minute and full recovery through the subsequent time. Coronary flow was augmented significantly in the 3 minute [96*6.2%, p<0.001] and then sustained above baseline values. Among the Croup I, II, and III, all hemodynamic values were significantly below preischemic levels. PGI2 relatively increased oxygen delivery [1.22*0.19ml/min, p<0.001] and myocardial oxygen consumption [0.90*0.13ml/min, p<0.001] during reperfusion period. Leakage of creatine kinase in the PGI2 group was 9.3*1.58IU/15min [p<0.001]. This was significantly lower than Group I [33.0*2.68 IU/15min]. The water content of PCI2 treated hearts [81*0.9%, p<0.001] was also lower than the other groups.

• Journal of Chest Surgery
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• v.37 no.2
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• pp.119-130
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• 2004

Decrease in cardiac function after open heart surgery is due to an ischemia induced myocardial damage during surgery, and ischemic preconditioning, a condition in which the myocardial damage does not accumulate after repeated episodes of ischemia but protects itself from damage after prolonged ischemia due to myocytes tolerating the ischemia, is known to diminish myocardial damage, which also helps the recovery of myocardium after reperfusion, and decreases incidences of arrythmia. Our study is performed to display the ischemic preconditioning and show the myocardial protective effect by applying cardioplegic solution to the heart removed from rat. Material and Method: Sprague-Dawley male rats were used, They were fixed on a modified isolated working heart model after cannulation. The reperfusion process was according to non-working and working heart methods and the working method was executed for 20 minutes in which the heart rate, aortic pressure, aortic flow and coronary flow were measured and recorded. The control group is the group which the extracted heart was fixed on the isolated working heart model, recovered by reperfusion 60 minutes after infusion and preserved in the cardioplegic solution 20 minutes after the working heart perfusion and aortic cross clamp, The thesis groups were divided into group I, which ischemic hearts that were hypoxia induced were perfused by cardioplegic solution and preserved for 60 minutes; group II, the cardioplegic solution was infused 45 seconds (II-1), 1 minutes (II-2), 3 minutes (II-3), after the ischemia induction, 20 minutes after working heart perfusion and aortic cross clamp; and group III, hearts were executed on working heart perfusion for 20 minutes and aortic cross clamp was performed for 45 seconds (III-1), 1minute (III-2), 3 minutes (III-3), reperfused for 2 minutes to recover the heart, and then aortic cross clamping was repeated for reperfusion, all the groups were compared based on hemodynamic performance after reperfusion of the heart after preservation for 60 minutes. Result: The recovery time until spontaneous heart beat was longer in groups I, II-3, III-2 and III-3 to control group (p<0.01). Group III-1 (p<0.05) had better results in terms of recovery in number of heart rates compared to control group, and recovered better compared to II-1 (p<0.05). The recovery of aortic blood pressure favored group III-1 (p<0.05) and had better outcomes compared with II-1 (p<0.01). Group III-1 also showed best results in terms of cardiac output (p<0.05) and group III-2 was better compared to II-2 (p<0.05). Group I (p<0.01) and II-3 (p<0.05) showed more cardiac edema than control group. Conclusion: When the effects of other organs are dismissed, protecting the heart by infusion of cardioplegic solution after enforcing ischemia for a short period of time before the onset of abnormal heart beats for preconditioning has a better recovery effect in the cardioplegic group with preconditioning compared to the cardioplegic solution itself. we believe that further study is needed to find a more effective method of preconditioning.

• Journal of Chest Surgery
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• v.18 no.1
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• pp.46-53
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• 1985

A single aortic valve replacement using the lonescu-Shiley bovine pericardial xenograft valve was performed in 66 consecutive patients during the period from February, 1979 to June, 1984. They were 49 males and 17 females with ages ranging from 9 to 61 [mean, 31.113.1] years, and 9 of them were children younger than 15 years of age. Twenty-seven patients [40.9%] required the combined operative procedures to either other valvular lesions or congenital defects. There were 9 early deaths within 30 days of surgery [operative mortality rate, 13.6%] and 2 late deaths thereafter [late mortality rate, 3.0%; or 1.75%/patient-year]. The 57 early survivors were followed for a total duration of 114.2 patient-years [mean, 24.016.0 months]. Four patients experienced thromboembolic complication with no death [3.50%/patient-year]; one died from intracranial bleeding related to anticoagulation [0.88%/patient-year]; one recovered from prosthetic valve endocarditis [0.88%/patient-year]; and four developed aortic regurgitant murmur with none or minimal cardiac symptoms and they were classified into cases of tissue valve failure [3.50%/patient-year]. The actuarial survival rate was 82.34.7% at 6 years, and the actuarial probabilities of freedom from thromboembolism and valve failure were 93.33.9% and 89.15.8% at postoperative 6 years respectively Symptomatic improvement was excellent in most late survivors at the follow-up end with the mean of NYHA Classes of 1.040.19 while the one was 2.290.67 at the time of operation. Excluding the higher operative mortality rates, these clinical results are fully comparable with the ones of reports from the major institutions using the porcine aortic or the bovine pericardial tissue valves and warrants the continued use of the xenograft valve in the aortic position. The importance of more detailed preoperative evaluation of the myocardial function and the need of improved myocardial preservation during surgery for the improved early clinical results were discussed.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.283-292
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• 2013

Ginsenosides are divided into two groups based on the types of the panaxadiol group (e.g., ginsenoside-Rb1 and -Rc) and the panaxatriol group (e.g., ginsenoside-Rg1 and -Re). Among them, ginsenoside-Re (G-Re) is one of the compounds with the highest content in Panax ginseng and is responsible for pharmacological effects. However, it is not yet well reported if G-Re increases the hemodynamics functions on ischemia (30 min)/reperfusion (120 min) (I/R) induction. Therefore, in the present study, we investigated whether treatment of G-Re facilitated the recovery of hemodynamic parameters (heart rate, perfusion pressure, aortic flow, coronary flow, and cardiac output) and left ventricular developed pressure (${\pm}dp/dt_{max}$). This research is designed to study the effects of G-Re by studying electrocardiographic changes such as QRS interval, QT interval and R-R interval, and inflammatory marker such as tissue necrosis factor-${\alpha}$ (TNF-${\alpha}$) in heart tissue in I/R-induced heart. From the results, I/R induction gave a significant increase in QRS interval, QT interval and R-R interval, but showed decrease in all hemodynamic parameters. I/R induction resulted in increased TNF-${\alpha}$ level. Treatment of G-Re at 30 and $100{\mu}M$ doses before I/R induction significantly prevented the decrease in hemodynamic parameters, ameliorated the electrocardiographic abnormality, and inhibited TNF-${\alpha}$ level. In this study, G-Re at $100{\mu}M$ dose exerted more beneficial effects on cardiac function and preservation of myocardium in I/R injury than $30{\mu}M$. Collectively, these results indicate that G-Re has distinct cardioprotectective effects in I/R induced rat heart.

• Journal of Chest Surgery
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• v.17 no.4
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• pp.557-564
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• 1984

Of the valve replacement patients operated between 1983 and June, 1984, 75 patients need more than 60 minutes of aortic cross-clamping time. 42 patients performed single valve replacement [35 MVR, 7 AVR with or without TAP] and remainder needs double valve replacement with or without TAP. The average aortic clamping time was 95.1 minutes. They need 30 minutes more extra-corporeal circulation time than aortic clamping time. The patients were divided into two groups by usage of cardioplegic solution. Group I [n=31] with Bretschneider solution and group II with potassium cardioplegic solution [M.G.H. modification] were analyzed by extra-corporeal circulation data,/CG and Echocardiography findings, and clinical data. There was no difference between two groups in Bivon addition amounts [cc/kg] and E.F. and S.F. by echocardiography, group I need 1 more electrocardioversion to convert sinus rhythm postoperatively. Also no difference could be found in patients whose preoperative C.I. was above 2.0 between two group. But significant postoperative decrease in E.F. was found in group I whose preoperative C.I. was below 2.0. Relatively longer ECC time was also needed in same group. Ischemic changes in ECG and low cardiac output syndrome was, however more prevalent in groupII. As a whole, the clinical data was satisfactory with both cardioplegic solution in clinical practice.

• Journal of Chest Surgery
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• v.29 no.8
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• pp.807-815
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• 1996

The protective effect of'ischemic preconditioning'on ischemid-reperfusion injury of heart has been reported in various animal species. but without known mechAnism in detail, In An attempt to investigate the cardioprotective mechanism of ischemic preconditioning, we examined the effects of nitric oxide(UO) synthesis in preconditioned heart of rat The isolated hearts perfused by Langendorfr's method were ex- posed to 30min global ischemia followed by 30min reperfusion with oxygenated Krebs-Henseleit(K-H) sol- ution. Ischemic preconditioning was performed with three episodes of Sm n ischemia and Smin repeyfusion before the induction of prolong ischemia(30min)-reperfusion(30min). Ischemic preconditioning prevented the depression of cardiac function(left ventricular pressure .K heart rate) observed in the ischemia- reperfusion hearts and reduced the release of lactate dehydrogenase during the reperfusion period. On electromicroscopic pictures, myocardial ultrastructures wore relatively well preserved in isthemic preconditioned hearts. N6_nitro-L-arginine methyl ester(L-NAME) an inhibitor of L-arginine citric oxide pathway, was infused at a rate O.Smllmin In a dose of 10mg kg-1 before the initial ischemic preconditioning. neither the protection of cardiac function nor the reduction of LDH releAse in ischemic preconditioning hearts was altered in the presence of added L-NAME On ultrastructural finding, the preservation of morphology in ischemic preconditioning heart was not change by the pretreatment of L-UAME. The failure of the WO synthesis inhibitor to reduce t e effect of ischemic preconditioning may be related to be species specific in that NO may allot be the trigger for ischemic preconditioning in rats.

• Journal of Chest Surgery
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• v.16 no.1
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• pp.65-74
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• 1983

Fifty cases of open heart surgery were done in the Department of Thoracic and Cardiovascular Surgery, Busan National University Hospital during 16 months from July, 1981 to October, 1982. The clinical data were analyzed and summerized as follows. 1. There were 34 cases (68%) of congenital anomalies and 16 cases (32%) of acquired heart diseases. Among the congenital cases, 27 were acyanotic and 7 were cyanotic. All of the acquired heat diseases, 16 cases were valvular diseases and they had valvular replacement surgery. 2. The age distribution of the congenital anomalies ranged from 6 to 27 years with mean age of 14.2 years, and the acquired heart diseases from 18 to 44 years mean age of 27.5 years. The difference of sex distribution was no significance. 3. The clinical minifestations in acyanotic congenital anomalies were exertional dyspnea (81.5%), recurrent respiratory infection (55.6%) and palpitation (22.2%), and in cyanotic congenital anomalies were exertional dyspnea (100%), syncope(57.1%) and growth retardation(57.1%), and in acquired heart diseases were dyspnea(100%), edema (62.5%) and general weakness (62.5%) 4. During the cardiopulmonary bypass, mild to moderate core cooling was performed and added topical cooling for more accurate myocardial preservation. 5. Two kinds of cardioplegic solution used in our institute were Bretschneider solution for the first 7 cases and mixed Harmann's solution 1 L with glucose 5gm, potassium chloride 26 mEq and sodium bicarbonate 24 mEq, making 376 mosmol/L and pH 8.3 at $25^{\circ}C$, for the rest 43 cases. 6. Various kinds of postoperative complications occurred in 14 cases (28%) and showed overall mortality 12%. The mortality along with each disease was 7.4% in congenital acyanotic cases, 42.9% in congenital cyanotic cases and 6.3% in acquired valvular diseases. 7. Pre-and postoperative diagnostic incompatibility was seen in 6 cases (12%). 8. The artificial valves used in the replacement surgery were lonescu-Shiley bovine xenograft in 6 cases and Carpentier-Edwards porcine xenograft in 10 cases.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.482-489
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• 2020

G protein-coupled receptor kinase 5 (GRK5) has been considered as a potential target for the treatment of heart failure as it has been reported to be an important regulator of pathological cardiac hypertrophy. To discover novel scaffolds that selectively inhibit GRK5, we have identified a novel small molecule inhibitor of GRK5, KR-39038 [7-((3-((4-((3-aminopropyl)amino)butyl)amino)propyl)amino)-2-(2-chlorophenyl)-6-fluoroquinazolin-4(3H)-one]. KR-39038 exhibited potent inhibitory activity (IC₅₀ value=0.02 µM) against GRK5 and significantly inhibited angiotensin II-induced cellular hypertrophy and HDAC5 phosphorylation in neonatal cardiomyocytes. In the pressure overload-induced cardiac hypertrophy mouse model, the daily oral administration of KR-39038 (30 mg/kg) for 14 days showed a 43% reduction in the left ventricular weight. Besides, KR-39038 treatment (10 and 30 mg/kg/day, p.o.) showed significant preservation of cardiac function and attenuation of myocardial remodeling in a rat model of chronic heart failure following coronary artery ligation. These results suggest that potent GRK5 inhibitor could effectively attenuate both cardiac hypertrophy and dysfunction in experimental heart failure, and KR-39038 may be useful as an effective GRK5 inhibitor for pharmaceutical applications.

• Journal of Chest Surgery
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• v.38 no.2 s.247
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• pp.101-109
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• 2005

Background: In sudden cardiac arrest, the effective maintenance of coronary artery blood flow is of paramount importance for myocardial preservation as well as cardiac recovery and patient survival. The purpose of this study was to directly compare the effects of pulsatile and non-pulsatile circulation to coronary artery flow and myocardial preservation in cardiac arrest condition. Material and Method: A cardiopulmonary bypass circuit was constructed in a ventricular fibrillation model using fourteen Yorkshire swine weighing $25\~35$ kg each. The animals were randomly assigned to group I (n=7, non-pulsatile centrifugal pump) or group II (n=7, pulsatile T-PLS pump). Extra-corporeal circulation was maintained for two hours at a pump flow of 2 L/min. The left anterior descending coronary artery flow was measured with an ultrasonic coronary artery flow measurement system at baseline (before bypass) and at every 20 minutes after bypass. Serologic parameters were collected simultaneously at baseline, 1 hour, and 2 hours after bypass in the coronary sinus venous blood. The Mann-Whitney U test of STATISTICA 6.0 was used to determine intergroup significances using a p value of < 0.05. Result: The resistance index of the coronary artery was lower in group II and the difference was significant at 40 min, 80 min, 100 min and 120 min (p < 0.05). The mean velocity of the coronary artery was higher in group II throughout the study, and the difference was significant from 20 min after starting the pump (p < 0.05). The coronary artery blood flow was higher in group II throughout the study, and the difference was significant from 40 min to 120 min (p < 0.05) except at 80 min. Serologic parameters showed no differences between the groups at 1 hour and 2 hours after bypass in the coronary sinus blood. Conclusion: In cardiac arrest condition, pulsatile extracorporeal circulation provides more blood flow, higher flow velocity and less resistance to coronary artery than non-pulsatile circulation.

• Journal of Chest Surgery
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• v.31 no.4
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• pp.353-361
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• 1998

Hypothermia is widely acknowledged as fundamental component of myocardial protection during cardiac operations. Although it prolongs the period of ischemic arrest by reducing oxygen demands, hypothermia is associated with a number of major disadvantages, including its detrimental effects on enzymatic function, energy generation, and cellular integrity. The ideal way to rotect the heart is to electromechanically arrest it and perfus it with blood that is aerobic arrest. However alternative technique has been developed, based on the principles of electromechanical arrest and normothermic aerobic perfusion using continuous warm blood cardioplegia. To determine if continuous warm blood cardioplegia was beneficial in clinical practice during valvular surgery, we studied two groups of patients matched by numbers and clinical characteristics. Group included is 31 patients undergoing valvular surgery who received intermittent cold crystalloid cardioplegia. Group II included 30 patients undergoing valvular surgery who received continuous warm blood cardioplegia. Our results suggest that the heartbeat in 100% of patients treated with continuous warm blood cardioplegia converted to normal sinus rhythm spontaneously after the removal of the aortic cross-clamp, compared to only 31% of the cold cardioplegia group. After operation, pericardial closure rate was 90% area in the warm group, compared to 35% area in the cold group. 12 hours after the operation, the total amount of urine output in the warm group was greater than that in the cold group(2863${\pm}$127 ml versus 2257${\pm}$127 ml; p<0.05). After the operation, left diaphragmatic elevation developed in 55% of the cold group but in 0% of the warm group. CK-MB level in the warm group was significantly lower than cold group(2.28${\pm}$0.62 versus 9.96${\pm}$2.12; p<0.01) 1 hour after operation and CK-MB level in the warm group was significantly lower than cold group(1.80${\pm}$1.01 versus 6.00${\pm}$1.74; p<0.05) 12hours after operation. Continuous warm blood cardioplegia is at least as safe and effective as hypothermic technique in patients undergoing cardiac valvular surgery. Conceptually, this represents a new approach to the problem of maintaining myocardial preservation during cardiac operations.