• Journal of Chest Surgery
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• v.31 no.6
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• pp.567-575
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• 1998

Panax Ginseng C.A. Meyer has been known for hundreds of years as the most valuable drug having mysterious effects among all the herbal medicines and plants in Korea. Also, many experimental studies have been performed recently that the various effects were identified and applied clinically. So we attempted an experimental study on the effect of ginsenoside Rg1 mixtures in an isolated rat heart with the use of the Langendorff model. The objective of this study was to determine whether this ginsenoside Rg1 mixtures would protect the myocardial injury after ischemic arrest and reperfusion. Isolated rat hearts were allowed to equilibrate for 20 minutes and were then subjected to 15 minutes of normothermic ischemia. After this ischemic period, isolated rat hearts were allowed to reperfusion for 10 minutes(Ischemic Group). In other group , isolated rat hearts were perfused for 60 minutes continuously with normothermia( Normothermic Group). Hemodynamic and biochemical parameters such as heart rate, left ventricular pressure, +dp/dt max, coronary blood flow and cardiac enzymes were measured during initial perfusion, ischemia, reperfusion period (Ischemic group) and 20, 40 and 60 minutes after continuous perfusion(Normothermic group). After completion of the experiment, this data was evaluated and the following results were obtained. 1. Heart rates showed an increase in both ischemic and normothermic experimental groups, but statistically significant differences were not identified. 2. LVP(Left Ventricular Pressure) showed statistically significant differences in both ischemic and normothermic experimental groups(p<0.005, p<0.01). 3. +dp/dt max showed statistically significant differences in both ischemic and normothermic experimental groups(p<0.01, p<0.01). 4. There were no statistically significant differences in coronary blood flow and cardiac cenzymes in all groups, but experimental groups seemed to have better protection and recovery. These results suggest that ginsenoside Rg1 mixtures has a protective effect on the myocardial injury after ischemia and reperfusion.

• Journal of Sasang Constitutional Medicine
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• v.13 no.1
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• pp.70-78
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• 2001

ADR유발성 심근독성에 대한 심근세포의 손상기전을 규명하기 위해 ADR의 독성을 MTT정량, NR정량, LDH활성도 및 심박동을 측정하였다. 배양된 심근세포에서 청심연자탕 전탕액의 심근세포 보호효과는 LDH활성도 측정과 심박동 측정을 통해 관찰할 수 있었다. 이 실험을 통해 다음과 같은 결과를 얻을 수 있었다. 1. ADR은 배양심근세포에서 세포의 생존능력을 떨어뜨렸고, LDH의 활성도를 높였으며, 심박동수를 감소시켰다. 2. 청심연자탕 전탕액은 배양심근세포에서 ADR에 의해 증가된 LDH 활성도를 유의하게 감소시켰다. 3. 청심연자탕 전탕액은 배양심근세포에서 ADR에 의해 감소된 심박동을 유의하게 증가시켰다. 이상의 결과를 통해 ADR은 신생 마우스에서 적출해낸 배양 심근세포에서 독성효과를 나타냈음을 알 수 있었으며, 청심연자탕 전탕액은 ADR에 의해 유발된 심근세포독성에 매우 효과적으로 방어효과를 나타냄을 알 수 있었다.

• 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.

• Proceedings of the KTCVS Conference
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• 1993.06a
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• pp.14-14
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• 1993

• Journal of Chest Surgery
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• v.37 no.9
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• pp.735-741
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• 2004

Blood cardioplegia is known as an established cardioplegic solution during open heart surgery. Recently, the Histidine-Tryptophan-Ketoglutarate (HTK) solution has been introduced as a cardioplegia in Korea. This study was designed to compare the myocardial protective effect between the cold blood cardioplegia (CBC) and HTK solution. Material and Method: Forty patients who underwent valve surgery or coronary artery bypass surgery were randomly divided into CBC group (n=20) and HTK group (n=20). The perioperative hemodynamic and clinical data were analyzed. The concentration of CK-MB, Troponin 1 and Lactate from coronary sinus and radial arterial blood were compared for the evaluation of the myocardial damage. The postoperative serial CK-MB levels were measured. Result: The characteristics of preoperative patients were similar in two groups. The hemodynamic parameters and postoperative clinical data were also similar between the two groups. There were no statistical significances between the CBC and HTK group in the difference of biochemical markers: Δ CK-MB (15.3$\pm$26.0 vs 19.3$\pm$14.3), ΔTro-1 (2.4$\pm$4.9 vs 2.0$\pm$2.20), ΔLac (1.6$\pm$1.0 vs 1.9$\pm$2.5). The serial CK-MB levels were not significantly different between the two groups. Conclusion: These results suggested that the myocardial protective effect of HTK solution was similar to cold blood cardioplegia during open heart surgery.

• Journal of Chest Surgery
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• v.35 no.1
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• pp.11-19
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• 2002

Background: Ischemia-reperfusion myocardial injury is an important factor to determine the early and the late mortality of transplanted patients. Recently, modulation of the cytosolic NADH/NAD+ ratio by Pyruvate and aspartate was tested to Protect the heart from ischemia-reperfusion injury. Material and Method: We added pyruvate and aspartate to the University of Wisconsin solution, and evaluated their effect on myocardial protection. We used 16 piglet(age 1 to 3 days) hearts. Eight hearts were arrested with and stored in the University of Wisconsin solution(UW solution) for 24 hours(control group), and the other eight hearts were arrested with and stored in the modified UW solution added pyruvate(3mmol/L) and aspartate(2 mmol/L)(test group). All hearts underwent modified reperfusion with blood cardioplegic solution followed by conversion to a left-sided working model with perfusion from a support pig. And then, we measured stroke work index(SWI), high-energy phosphate stores, and myocardial water content of the hearts. SWI was calculated at left ventricular end-diastolic pressures of 3, 6, 9, and 12 mmHg after 60 and 120 minutes reperfusion, respectively, Result: At 60 minutes and 120 minutes after reperfusion, SWI was higher in the test group than in the control group significantly. The levels of AMP, ADP, ATP of the test group were also higher. But, the creatine phosphate level and myocardial water content were similar in the two groups. Conclusion: From these results, we could Prove that pyruvate and aspartate enhance cardiac contractility and high-energy phosphate stores after ischemia.

• Journal of Chest Surgery
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• v.32 no.9
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• pp.773-780
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• 1999

Background: It has been demonstrated that brief periods of calcium depletion and repletion (calcium-free preconditioning, CP) have cardioprotective effects as seen in ischemic preconditioning(IP) which enhances the recovery of post-ischemic contractile dysfunction and reduces the incidence of reperfusion-induced arrhythmia or infarct size after a prolonged ischemia. In the present study, we tested this paradoxical phenomenon in isolated rabbit hearts. Material and Method: Hearts isolated from New Zealand white rabbits(1.5∼2.0 Kg body weight) were perfused with Tyrode solution using the Langendorff technique. After stabilizing the baseline hemodynamics, the hearts were subjected to 45 minutes of global ischemia followed by 120 minutes of reperfusion with IP(IP group, n=7) or without IP (ischemic control group, n=7). IP was induced by a single episode of 5 minutes global ischemia and 10 minutes reperfusion. In the CP group(n=7), the hearts were subjected to perfusion with Tyrode solution with calcium depletion for 5 minutes and repletion for 10 minutes, and 45 minutes of ischemia and 120 minutes of reperfusion. Left ventricular function including developed pressure, dP/dt, heart rate, left ventricular end-diastolic pressure and coronary flow was measured. Infarct size was determined by staining with 1% triphenyltetrazolium chloride and planimetry. Data were analyzed by a one-way analysis of variance and Tukey's post-hoc test. Result: In comparison with the ischemic control group, IP significantly enhanced the recovery of the left ventricular function including the left ventricular developed pressure, contractility, and coronary flow; in contrast, these functional parameters of the CP group tended to be lower than those of the ischemic control group. However, the infarct size was significantly reduced by IP or CP(p<0.05). Conclusion: These results suggest that in isolated Langendorff-perfused rabbit heart model, CP(induced by single episode of 5 minutes calcium depletion and 10 minutes repletion) could not improve the post-ischemic contractile dysfunction(after a 45-minute global ischemia) but it has an infarct size-limiting effect.

• Journal of Chest Surgery
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• v.31 no.9
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• pp.837-844
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• 1998

Background: Adenosine is secreted by myocardial cells during myocardial ischemia or hypoxia. It has many beneficial effects on arrhythmias, myocardial ischemia, and reperfusion ischemia. Although many investigators have demonstrated that cardioplegia that includes adenosine shows protective effects in myocardial ischemia or reperfusion injury, reports of the optimal dose of adenosine in cardioplegic solutions vary. We reported the results of beneficial effects of single dosage(0.75 mg/Kg/min) adenosine by use of self-made Langendorff system. But it is uncertain that dosage was optimal. The objective of this study is to determine the optimal dose of adenosine in cardioplegic solutions. Material and Method: We used a self-made Langendorff system to evaluate the myocardial protective effect. Isolated rat hearts were subjected to 90 minutes of deep hypothermic arrest(15$^{\circ}C$) with modified St. Thomas' Hospital cardioplegia including adenosine. Myocardial adenosine levels were augmented during ischemia by providing exogenous adenosine in the cardioplegia. Three groups of hearts were studied: (1) group 1 (n=10) : adenosine - 0.5 mg/Kg/min, (2) group 2(n=10): adenosine -0.75 mg/Kg/min, (3) group 3 (n=10) : adenosine -1 mg/Kg/min. Result: Group 3 resulted in a significantly rapid arrest time of the heart beat(p<0.05) but significantly slow recovery time of the heart beat after reperfusion(p<0.05) compared to groups 1 and 2. Group 2 showed a better percentage of recovery(p<0.05) in systolic aortic pressure, aortic overflow volume, coronary flow volume, and cardiac output compared to groups 1 and 3. Group 1 showed a a better percentage of recovery(p<0.05) in the heart rate compared to the others. In biochemical study of drained reperfusates, CPK and lactic acid levels did not show significant differences in all of the groups. Conclusion: We concluded that group 2 [adenosine(0.75 mg/Kg/min) added to cardioplegia] has better recovery effects after reperfusion in myocardial ischemia and is the most appropriate dosage compared to group 1 and 3.

• Journal of Chest Surgery
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• v.36 no.9
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• pp.638-645
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• 2003

The purposes of this study were to evaluate the effect of myocardial protection with our cold blood cardioplegic solution and to observe the relationship between ultrastructural study and other evaluation methods and its effectiveness. Material and Method: We evaluated the changes of myocardial ultrastructure using semi-quantitative scoring system, CK-MB fraction, SGOT and LDH1/LDH2, and EKG in 18 patients undergoing valvular heart surgery and coronary artery bypass grafting (CABG). Right atrial auricular biopsies were taken before the cardiopulmonary bypass (CPB) and shortly after the end of CPB. Myocardium-related serum enzymes ＆ EKG were checked for 3 days of postoperative period and their postoperative peak enzyme value and observed new Q wave ＆ ST segment elevation in EKG were choosen. Result: There were 8 males and 10 females, and their mean age was 55.6$\pm$13. Eight patients underwent valvular heart surgery and ten coronary artery bypass grafting, The mean CPB time was 119$\pm$29 minutes and the mean aortic cross-clamp (ACC) time was 75.4$\pm$24 minutes. Before the start of CPB, the mean mitochondrial score was 4.28$\pm$0.53 and after the end of CPB, it significantly increased to 2.35$\pm$0.79. There was no evidence of perioperative myocardial infarction in terms of myocardiumrelated serum enzyme value and Q wave and ST change in EKG. There was no significant relationship between pre-CPB and post-CPB mitochondrial score and the mean time of CPB and ACC, and the mean value of postoperative peak CK-MB, SGOT and LDH1/LDH2, but there was relatively positive correlation of CPB time with peak LDH1/LDH2. Conclusion: Despite the apparent satisfactory results in myocardium-related serum enzymes ＆ EKG, with this study using the cold blood cardioplegic solution, there were many changes in myocardial ultrastructures, and more studies are needed to obtain further information.

• 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.