• The Korean Journal of Physiology and Pharmacology
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• v.23 no.5
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• pp.329-334
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• 2019

Diabetes is associated with an increased risk of cardiovascular complications. Dipeptidyl peptidase-4 (DPP-IV) inhibitors are used clinically to reduce high blood glucose levels as an antidiabetic agent. However, the effect of the DPP-IV inhibitor gemigliptin on ischemia/reperfusion (I/R)-induced myocardial injury and hypertension is unknown. In this study, we assessed the effects and mechanisms of gemigliptin in rat models of myocardial I/R injury and spontaneous hypertension. Gemigliptin (20 and 100 mg/kg/d) or vehicle was administered intragastrically to Sprague-Dawley rats for 4 weeks before induction of I/R injury. Gemigliptin exerted a preventive effect on I/R injury by improving hemodynamic function and reducing infarct size compared to the vehicle control group. Moreover, administration of gemigliptin (0.03% and 0.15%) powder in food for 4 weeks reversed hypertrophy and improved diastolic function in spontaneously hypertensive rats. We report here a novel effect of the gemigliptin on I/R injury and hypertension.

• Journal of Chest Surgery
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• v.22 no.6
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• pp.901-913
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• 1989

This study was investigated under the postulation that activation of intracellular calcium- calmodulin complex during ischemia-reperfusion leads to myocardial injury. The protective effects of calcium channel blocker, diltiazem and calmodulin inhibitors, trifluoperazine, flunarizine and calmidazolium from ischemic injury in rat hearts were observed by using Langendorff apparatus when the antagonists were infused for 3 min in the beginning of ischemia. Thereby, an increase in resting tension developed during 30-min ischemia was analyzed with regard to [1] the degree of cardiac functional recovery following 60-min reperfusion, [2] changes in biochemical variables evoked during 30-min ischemia. The results obtained were as follows: l. In the ischemic group, the resting tension was increased by 4.1*0.2 g at 30-min ischemia. However, the increase in resting tension was markedly reduced not only by pretreatment with diltiazem [3.3 p M] but also with calmodulin inhibitors, trifluoperazine [3.3 p M], flunarizine [0.5 p M] and calmidazolium [0.5 p M], respectively. 2. Recovery of myocardial contractility, +dF /dt and coronary flow were much reduced when evoked by reperfusion in the ischemic group. These variables were significantly improved either by pretreatment with diltiazem or with calmodulin inhibitors. 3. The resting tension increment evoked during ischemia was significantly inversely correlated with the degree of cardiac function recovered during reperfusion. 4. Following 30-min ischemia, the production of malondialdehyde and release of lysosomal enzyme were much increased in association with a decrease in creatine kinase activity. 5. The increases in malondialdehyde production and release of free lysosomal enzyme were suppressed by pretreatment with calmodulin inhibitors as well as diltiazem. Likewise, the decrease of creatine kinase activities was prevented by these calcium antagonists. With these results, it is indicated that a increase in resting tension observed during ischemia has an inverse relationship to the cardiac function recovered following reperfusion, and further, the later may be significantly dependent on the degree of biochemical alterations occurred during ischemia such as decrease in creatine kinase activity, increased production of malondialdehyde and increased release of free lysosomal enzyme. Thus it is concluded that calmodulin plays a pivotal role in the process of ischemic injury.

• Journal of Chest Surgery
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• v.29 no.10
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• pp.1076-1080
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• 1996

The results about the myocardial protection of recta of the nitric oxide precursor L-arginine upon reperrusion injury after ischemia are diverse. These diversities may be model dependent. Experiments were designed and performed to investigate myocardial protection effects according to the concentration of L-arginine. The Isolated rat hearts were subjected in a 30 minutes oi normothermic ischemia and reperfused for 30 minutes with reperfusate containing 0, 1, 2, 3, 4 moil L-arginine. After 30 minutes of reperfusion, group with 1 and 2 mM/L L-arginine showed a trend of better recovery in left ventricular systolic function(left ventricular developed pressure, positive maximum dpfdt), diastolic function(negative maximum dpfdt) and coronary flow compared to control group(reperfusate no L-arginine). Recovery was impaired with a higher concentration, and at 4 moil L-arginine r covery was worse than control(p (0, 05). These results suggest that optimal concentration of L-arginine Is Important or the recovery of myocardial and endothelial function after ischemia and reperfusion.

• Korean Circulation Journal
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• v.54 no.5
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• pp.233-252
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• 2024

Background and Objectives: Myocardial ischemia-reperfusion injury (MIRI) refers to the damage of cardiac function caused by restoration of blood flow perfusion in ischemic myocardium. However, long non-coding RNA prostate androgen regulated transcript 1 (PART1)'s role in MIRI remain unclear. Methods: Immunofluorescence detected LC3 expression. Intermolecular relationships were verified by dual luciferase reporter assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry and transferase-mediated dUTP nick-end labeling (TUNEL) assays analyzed cell viability and apoptosis. The release of lactate dehydrogenase was tested via enzyme-linked immunosorbent assay (ELISA). Left anterior descending coronary artery surgery induced a MIRI mouse model. Infarct area was detected by 2,3,5-triphenyltetrazolium chloride staining. Hematoxylin and eosin staining examined myocardial injury. ELISA evaluated myocardial marker (creatine kinase MB) level. Results: PART1 was decreased in hypoxia/reoxygenation (H/R) induced AC16 cells and MIRI mice. PART1 upregulation attenuated the increased levels of Bax, beclin-1 and the ratio of LC3II/I, and enhanced the decrease of Bcl-2 and p62 expression in H/R-treated cells. PART1 upregulation alleviated H/R-triggered autophagy and apoptosis via miR-302a-3p. Mechanically, PART1 targeted miR-302a-3p to upregulate transcription factor activating enhancer-binding protein 2C (TFAP2C). TFAP2C silencing reversed the protected effects of miR-302a-3p inhibitor on H/R treated AC16 cells. We further established TFAP2C combined to dual-specificity phosphatase 5 (DUSP5) promoter and activated DUSP5. TFAP2C upregulation suppressed H/R-stimulated autophagy and apoptosis through upregulating DUSP5. Overexpressed PART1 reduced myocardial infarction area and attenuated MIRI in mice. Conclusion: PART1 improved the autophagy and apoptosis in H/R-exposed AC16 cells through miR-302a-3p/TFAP2C/DUSP5 axis, which might provide novel targets for MIRI treatment.

• Journal of Chest Surgery
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• v.19 no.2
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• pp.217-224
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• 1986

Using an isolated rat heart preparation under both aerobic and ischemic condition, we observed the myocardial protective effect of verapamil cardioplegia. Isolated working hearts were subjected to global ischemia at 25oC. Before ischemic arrest, rat hearts were treated with cold potassium cardioplegic solution [K=30 mEq/L] in control group and cold potassium cardioplegic solution added with verapamil [1 mg/L] in other group. After 30 min. of ischemia, hemodynamic parameters and creatine kinase leakage in coronary effluent were observed. Verapamil group exhibited greater percent of recovery in aortic pressure [p<0.01], aortic flow [p<0.01], and stroke volume [p<0.05]. Although there were no significant difference in creatine kinase leakage and the percent recovery of cardiac output between verapamil and control group, verapamil group showed better myocardial function. But the time to recover regular sinus rhythm was significantly [p<0.001] prolonged in verapamil group.

• Journal of Biomedical Engineering Research
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• v.15 no.4
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• pp.407-412
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• 1994

This paper describes the construction of an anisotropic three dimensional ventricular model based on the bidomain model. The cardiac activation process in the normal cardiac cell and the myocardial ischemic cell are simulated by the Huygen's principle. The depolarization process in the myocardial ischemia displays the delayed activation compared to the normal state. The repolarization process is simulated by the myocardial potential at the arbitrary ellapsed time after activation process. Using the potential data, the equivalent cardiac source at the arbitrary time can be computed. In conclusion, this simulation suggests the possibilities of the depolarization and the repolarization process in the normal and abnormal myocardiac cells.

• The Korean Journal of Nuclear Medicine
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• v.35 no.6
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• pp.398-400
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• 2001

The authors report a case of unsuspected myocardial ischemia detected during CoDe FDG PET (coincidence detection fluorodeoxyglucose positron emission tomogram) which was performed for the evaluation of a solitary pulmonary nodule. Camera-based FDG PET without attenuation correction often reveals false defect in the inferior wall of the left ventricle in normals due to excessive attenuation. However, this asymptomatic patient had increased uptake in the inferior wall suggesting ischemic myocardium. The scan finding was confirmed by Tl-201 myocardial SPECT and coronary angiogram. The patient then underwent successful PTCA of mild RCA and right ventricular branch followed by right upper lobectomy for small cell lung cancer.

• The Korean Journal of Nuclear Medicine
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• v.32 no.1
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• pp.1-9
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• 1998

Gated myocardial SPECT and attenuation correction gave birth to new insights into the pathophysiology of ischemic myocardial perfusion and function in clinical routine practice. Gated myocardial Tc-99m-compound SPECT improved diagnostic accuracy of coronary artery disease and enabled us to observe motion and thickening of myocardial walls as well as myocardial perfusion at the same time. Quantitative and qualitative assessment of myocardial performance and perfusion let us to understand the myocardial physiology in ischemia and infarction. In every patient who underwent gated perfusion SPECT, we will find ejection fraction, left ventricular volumes and regional wall motion. There are hopes to use gated TI-201 SPECT for the same purpose and to use gated SPECT for evaluation of wall motion and thickening at stress or immediate post-stress. Attenuation correction could improve diagnostic accuracy mainly by increasing normalcy ratio or performance of non-expert physicians. Both gated methods and attenuation correction improved specificity of non-expert physicians in diagnosing patients with moderate pretest likelihood. New imaging techniques will fill the desire of cardiologists to examine function and perfusion, and possibly metabolism in their clinical routine practice.

• 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.

• Korean Journal of Radiology
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• v.21 no.12
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• pp.1305-1316
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• 2020

In approximately 10% of patients with acute myocardial infarction (MI), angiography does not reveal an obstructive coronary stenosis. This is known as myocardial infarction with non-obstructive coronary arteries (MINOCA), which has complex and multifactorial causes. However, this term can be confusing and open to dual interpretation, because MINOCA is also used to describe patients with acute myocardial injury caused by ischemia-related myocardial necrosis. Therefore, with regards to this specific context of MINOCA, the generic term for MINOCA should be replaced with troponin-positive with non-obstructive coronary arteries (TpNOCA). The causes of TpNOCA can be subcategorized into epicardial coronary (causes of MINOCA), myocardial, and extracardiac disorders. Cardiac magnetic resonance imaging can confirm MI and differentiate various myocardial causes, while cardiac computed tomography is useful to diagnose the extracardiac causes.