• Journal of Chest Surgery
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• 제29권2호
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• pp.199-207
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• 1996

Adenosine을 함유한 심정지액의 심근 보호 효과심장수술에 있어서 허혈성 심정지는 거의 필연적인 과정이며 이로 인한 재관류후의 심근 손상은 심장 수술의 성패를 결정하는 가장 중요한 요소중의 하나이다. Adenosine은 강력한 혈관 확장제이며 칼슘통로에 길항하고 칼릅통로를 활성화 시컴으로 빠른 심정지를 유도하여 허혈성 심정지후 회복을 향상시킨다. Adenosine이 칼륨보다 빠른 심정지를 유도하고 허혈성 심정지후 혈역학적 회복을 향상시키는데 효과적이라는 가설을 검정하기위해 횐쥐의 심장을 Langendorff 장치에 연결하고 Krebs-Henseleit 완충액으로 관류 시킨후 심근 마비액을 이용하여 60분간 심정지를 시켰으며 심근 마비액은 구성에 따라 3군으로 분류하였다. A군(n=10), 칼륨을 함유하지 않은 St. Thomas 심정지액에 adenosine 10mmole/L 을 첨가. B군(n: 10), 칼륨을 함유한다. Thomas 심정지액에 adenosine 400 mol/L 을 첨가. C군(n=10), 기존의 St. Thomas 심정지액 Adenosine 을 함유한군(A군과 B군)은 대조군(C군)에 비해 빠른 심정지를 유발하였다(p<0.01). 관상동맥 관류량은 대조군과 비교하여 A군에서는 재관류 20분과 30분에 B군에서는 재관류 20분에 증가가 있었다(p<0.01). 수축기 동맥압은 A군과 B군에서 재관류 10분에 향상이 있었다(p<0.01). dpfdt는 A군에서 재관류 10분에 증가가 있었다(p<0.05). A군과 B군은 대동맥 관류량, 심박출량, 심박수에서도 C군에 비해 좋은 회복율을 보였으나 통계학적 유의성은 없었다. CPK 치는 A군에서 낮게 측정 되었다(p<0.01). 이상의 결과로 보아adenosine을 함유한 심정지액이 기존의 칼륨 심정지액에 비하여 빠른 심정지를 유도하였고 심장의 회복에 더욱 유리한 결과를 보여 주었다.

• 대한약리학회지
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• 제32권1호
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• pp.31-37
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• 1996

허혈전처치(IP)의 히혈-재관류손상에 대한 심근 보호작용의 기전을 규명하기 위한 일환으로 denosine에 의한 PKC자극이 허혈전처치의 주요 기전으로 작용할 가능성을 조사하였다. 흰쥐 적출심장의 Langendorff 관류 표본에서 실험적인 허혈(30분)-재관류(20분)손상을 유도하였고, 허혈전처치는 허혈-재관류 손상 유도 전에 5분 허혈-5분 재관류를 3회 반복하여 시행하였다. 심근 손상의 지표로 심수축기능, 세포질효소 유출을 측정하였다. Adenosine이 허혈전처치의 심보호 효과에 관여하는지를 관찰하기 위하여 adenosine수용체 억제제인 8-(p-sulfophenyl)-theophylline(SPT), Xanthine amine congener(XAC) 및 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)을 허혈전처치 유도 전에 투여하였다. 또한 PKC가 허혈전처치의 세포내 매개인자로 관여 할 가능성을 관찰하기 위하여 PKC활성 억제제인 polymyxin B 및 chelerythrine과 PKC translocation 억제제인 colchicine을 허혈전처치 유도 전에 투여하였다. 연구성적은 다음과 같다. 1) 허혈전처치는 허혈재관류 심장의 심기능의 저하를 현저히 회복시켜 심기능 회복률은 75%에 달하였다. 2) 허혈-재관류 심장에서 lactate dehydrogenase유출증가는 허혈전처치에 의해 현저히 저하되었다. 3) Adenosine 비선택적 차단제인 SPT와 Al 선택적 차단제인 DPCPX 및 XAC의 투여가 허혈전처치에 의한 심기능회복 및 LDH 유출 감소에 영향을 미치지 않았다. 4) PKC활성 억제제인 polymyxin B 와 chelerythrine을 처치시 히혈전처치 심장의 심기능 회복률이 현저히 감소되었으며 LHD 유출 역시 대조군 심장의 수준으로 증가하였다. 5) PKC translocation을 방해하는 colchicine도 허혈전처치의 심보호 효과를 억제시켰다. 이상의 결과들로부터 adenosine은 흰쥐 심장에서 허혈전처치의 심보호효과에 중요한 세포외 매개물질로 작용할 가능성이 희박하며, PKC는 흰쥐 심장에서 허혈전처치시 세포내 매개 인자로 관여하여 허혈전처치에 의한 심보호효과에 중요한 역할을 할 수 있으리라 사료된다.

• Korean Journal of Radiology
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• 제2권1호
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• pp.21-27
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• 2001

Objective: To identify and evaluate the lateral border zone by comparing the size and distribution of the abnormal signal area demonstrated by MR imaging with the infarct area revealed by pathological examination in a reperfused myocardial infarction cat model. Materials and Methods: In eight cats, the left anterior descending coronary artery was occluded for 90 minutes, and this was followed by 90 minutes of reperfusion. ECG-triggered breath-hold turbo spin-echo T2-weighted MR images were initially obtained along the short axis of the heart before the administration of contrast media. After the injection of Gadomer-17 and Gadophrin-2, contrast-enhanced T1-weighted MR images were obtained for three hours. The size of the abnormal signal area seen on each image was compared with that of the infarct area after TTC staining. To assess ultrastructural changes in the myocardium at the infarct area, lateral border zone and normal myocardium, electron microscopic examination was performed. Results: The high signal area seen on T2-weighted images and the enhanced area seen on Gadomer-17-enhanced T1WI were larger than the enhanced area on Gadophrin-2-enhanced T1WI and the infarct area revealed by TTC staining; the difference was expressed as a percentage of the size of the total left ventricle mass (T2= 39.2 %; Gadomer-17 =37.25 % vs Gadophrin-2 = 29.6 %; TTC staining = 28.2 %; p < 0.05). The ultrastructural changes seen at the lateral border zone were compatible with reversible myocardial damage. Conclusion: In a reperfused myocardial infarction cat model, the presence and size of the lateral border zone can be determined by means of Gadomer-17- and Gadophrin-2-enhanced MR imaging.

• Journal of Chest Surgery
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• 제25권4호
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• pp.347-355
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• 1992

The precise mechanism of the Excitation-Contraction Coupling is still uncertain. But the concept that Ca2+ induced Ca2+ release [CICR] from the Ryanodine receptor in the sarcoplasmic reticulum [foot structure] may play a major role in E-C coupling has been widely accepted since 1970`s. It is believed that increased cytosolic Ca2+ followed by CICR is main contributor for E-C coupling of striated muscle. Resulting phenomena of ischemic /post-reperfusion myocyte is increased cytosolic Ca2+, even to the absence of Ca2+ in reperfusate. So intracellular inhibitor to CICR might prevent the ischemic and reperfusion damage of myocardial cells. The relatively purified foot protein, especially heavy sarcoplasmic reticulum rich, of the skeletal muscle was incorporated into the black lipid bilayer [Phosphatidyl ethanolamine: Phosphatidyl serine=l: 1]. Under the steady state of membrane potential [+20 mV], ionic current through Ryanodine receptor was measured with Cs+ as charge carrier. In the cis chamber [Cytoplasmic side], Mg2+ strongly inhibited CICR of Ryanodine receptor[Kd=6.2 nM]. In conclusion, naturally existing intracellular free Mg2+ can inhibit CICR from intracellular Ca2+ reservior [heavy SR]. So post-ischemic or post-reperfusing myocardium could be preserved using additional free Mg2+ in cardioplegic solution or reperfusate, otherwise the optimal concentration is undetermined.

• Journal of Chest Surgery
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• 제27권7호
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• pp.563-570
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• 1994

Effect of ischemic preconditioning on left ventricular function after cardiac arrest in isolated rat heart.Ischemic preconditioning reduces infarct size caused by sustained ischemia. However, the effects of preconditioning on post ischemic cardiac function are not well-known. The objective of the present study was to determine whether preconditioning would improve the recovery of left ventricular functions after cardiac arrest in isolated rat heart model.Isolated rat hearts were allowed to equilibrate for 20 minutes and were then subjected to either 5 minutes of global, normothermic transient ischemia [Group 2 and 4] or not [Group 3]. A stabilization period of perfusion lasting 5 minutes after the termination of transient ischemia was followed by a standard global, normothermic 20 minute-ischemia and 35-minute reperfusion challenge [Group 3 and 4]. These following results were odtained.1. The recovery of left ventricular developed pressures showed no significant differences between Group 3 and Group 4 at 50 [P>0.3] and 85 minute [P>0.2].2. Heart rates showed no significant differences throughout all the course of experiment and between groups [P>0.5].3. The recovery of left ventricular maximum dP/dt showed no significant differences between Group 3 and Group 4 at 50 [P>0.1] and 85 minute [P>0.2].4. The recovery of pressure-rate products showed no significant differences between Group3 and Group 4 at 50 [P>0.5] and 85 minute [P>0.1].These results suggest that ischemic preconditioning does not provide significant benefit for the postischemic left ventricular functions in isolated rat hearts.

• Molecules and Cells
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• 제40권8호
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• pp.542-549
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• 2017

Cardiomyocyte apoptosis is initiated by various cellular insults and accumulated cardiomyocyte apoptosis leads to the pathogenesis of heart failure. Excessive reactive oxygen species (ROS) provoke apoptotic cascades. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme that converts cellular ROS into harmless products. In this study, we demonstrate that MnSOD is down-regulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Enhanced expression of MnSOD attenuates cardiomyocyte apoptosis and myocardial infarction induced by I/R injury. Further, we show that miR-23a directly regulates the expression of MnSOD. miR-23a regulates cardiomyocyte apoptosis by suppressing the expression of MnSOD. Our study reveals a novel model regulating cardiomyocyte apoptosis which is composed of miR-23a and MnSOD. Our study provides a new method to tackling apoptosis related cardiac diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제28권3호
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• pp.209-217
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• 2024

In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague-Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD.

• Journal of Chest Surgery
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• 제24권5호
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• pp.429-437
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• 1991

Beta hydroxytrimethylammonium butyrate[L-carnitine] is highly concentrated in myocardium and it is essential substance for transfer of fatty acids into the mitochondria. We respect that L-carnitine has protective action to myocardium during ischemia. I studied coronary flow and CK - MB isoenzyme of coronary effluent of Langendorff`s isolated rat heart model. As a control group 5 Sprague-Dowley species rat hearts were connected to Langendorff`s isolated rat heart model and perfused for 30 minutes with Kreb-Henseleit buffer solution. After cessation of perfusion for 30 minutes they were reperfused for 30 minutes. In experimental group 10 Sprague-Dowley species rat hearts were perfused with 10mmole /L of L-carnitine contained in Kleb-Henseleit buffer solution. In equilibrium state, coronary flow was 1.7 times greater in experimental group. During reperfusion, both group showed equally decreased flow amount of about 60% of that of equilibrium state. CK-MB isoenzyme level of perfused coronary fluid showed no significant difference in equilibrium state. In reperfusion. CK-MB isoenzyme levels of control group were 17.61$\pm$8. 68U/L at 25 minutes, 23.32$\pm$4.15U /L at 30 minutes; and in experimental group, 13.63$\pm$6. 08U/L at 15 minutes and 13.6$\pm$8.41U /L at 30 minutes respectively. Those values in both states showed significantly lower CK-MB level in experimental group. In conclusion, L-carnitine prevent ischemic myocardial damage during ischemic and reperfusion state of Langendorff`s isolated rat hearts and also I suggest the L-carnitine act potent coronary vasodilator during preischemic and postischemic states of rat hearts.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.283-289
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• 2013

This study was designed to evaluate the protective effect of Korean red ginseng (KRG) against ischemia/reperfusion (I/R) injury in isolated guinea pig heart. KRG has been shown to possess various ginsenosides, which are the major components of Panax ginseng. These components are known naturally occurring compounds with beneficial effects and free radical scavenging activity. The heart was induced to ischemia for 60 min, followed by 120 min reperfusion. The hearts were randomly allocated into five groups (n=8 for each group): normal control (N/C), KRG control, I/R control, 250 mg/kg KRG group and 500 mg/kg KRG group. KRG significantly increased hemodynamics parameters such as aortic flow, coronary flow and cardiac output. Moreover, KRG significantly increased left ventricular systolic pressure (LVSP), the maximal rate of contraction (+dP/$dt_{max}$) and maximal rate of relaxation (-dP/$dt_{max}$). Also, treatment of KRG ameliorated electrocardiographic index such as the QRS, QT and RR intervals. Moreover, KRG significantly suppressed the lactate dehydrogenase, creatine kinase-MB fraction and cardiac troponin I and ameliorated the oxidative stress markers such as malondialdehyde and glutathione. KRG was standardized through ultra performance liquid chromatograph analysis for its major ginsenosides. Taken together, KRG has been shown to prevent cardiac injury by normalizing the biochemical and oxidative stress.

• 대한핵의학회지
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• 제39권2호
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• pp.87-93
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• 2005

Coronary artery disease (CAD) has been increasing during the last decade and is the one of major causes of death. The management of patients with coronary artery disease has evolved considerably. There are two main strategies in the management of CAD, complementary, not competitive, each other; the pharmacologic therapy to prevent and treat CAD and the percutaneous coronary Intervention (PCI) to restore coronary flow. Antiplatelet drugs and cholesterol lowering drugs have central roles in pharmacotherapy. Drug eluting stent (DES) bring about revolutional changes in PCI. In the management of patients with 57 segment elevation acute myocardial infarction (AMI), there has been a debate on the better strategy for the restoration of coronary flow. Thrombolytic therapy is widely available and easy to administer, whereas primary PCI is less available and more complex, but mote complete. Recently published evidences in the pharmacologic therapy including antiplatelet and stalin, and PCI including DES and reperfusion therapy in patients with ST segment elevation AMI were reviewed.