• Molecules and Cells
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• v.27 no.2
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• pp.159-166
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• 2009

Myocardial ischemia-reperfusion injury is a medical problem occurring as damage to the myocardium following blood flow restoration after a critical period of coronary occlusion. Oxygen free radicals (OFR) are implicated in reperfusion injury after myocardial ischemia. The antioxidant enzyme, Cu, Zn-superoxide dismutase (Cu, Zn-SOD, also called SOD1) is one of the major means by which cells counteract the deleterious effects of OFR after ischemia. Recently, we reported that a PEP-1-SOD1 fusion protein was efficiently delivered into cultured cells and isolated rat hearts with ischemia-reperfusion injury. In the present study, we investigated the protective effects of the PEP-1-SOD1 fusion protein after ischemic insult. Immunofluorescecnce analysis revealed that the expressed and purified PEP-1-SOD1 fusion protein injected into rat tail veins was efficiently transduced into the myocardium with its native protein structure intact. When injected into Sprague-Dawley rat tail veins, the PEP-1-SOD1 fusion protein significantly attenuated myocardial ischemia-reperfusion damage; characterized by improving cardiac function of the left ventricle, decreasing infarct size, reducing the level of malondialdehyde (MDA), decreasing the release of creatine kinase (CK) and lactate dehydrogenase (LDH), and relieving cardiomyocyte apoptosis. These results suggest that the biologically active intact forms of PEP-1-SOD1 fusion protein will provide an efficient strategy for therapeutic delivery in various diseases related to SOD1 or to OFR.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.145-152
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• 2017

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (non-cardiac) increases the tolerance of the myocardium to sustained ischemia-reperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection.

• Journal of Life Science
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• v.12 no.1
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• pp.33-42
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• 2002

In several species, a short period of ischemic preconditioning protects the heart by reducing the size of infarcts resulting from subsequent prolonged bouts of ischemia. The mechanism by which activation of ATP-sensitive $K^+$($K_ATP$) channels could provide the memory associated with ischemic preconditioning is still under debate. Several signal transduction pathways have been implicated in the mechanisms of protection induced by ischemic preconditioning. The exact receptor-coupled pathways involved in preconditioning remain to be identified. Likely extracellular agonists are those whose circulating levels increase under conditions that activate $K_ATP$ channels; these conditions include ischemia and ischemic preconditioning. Potential physiological agonists include the following: (1) nitric oxide; (2) catecholamine; (3) adenosine; (4) acetylcholine; (5) bradykinin and (6) prostacycline. The purpose of this review was to understand the mechanism by which biological signal transduction mechanism acts as a link in one or more known receptor-mediated pathways to increase $K_ATP$ channel activity during ischemic preconditioning.

• 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 Chest Surgery
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• v.23 no.6
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• pp.1067-1073
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• 1990

To clarify the changes of left ventricular function under normothermia, the time interval between the onset of ischemia and the beginning of contracture of left ventricle[TIC] were recorded in newborn piglet. Myocardial performance was assessed using intraventricular balloon to determine compliance and systolic function after 5 to 10 minutes interval per-fusing normothermic substrate free Krebs solution as a perfusate. The time to onset TIC was 29.5\ulcorner1.7 minutes and peak ischemic contracture was 46.7\ulcorner4.0 minutes[p<0.01]. In myocardial performance, systolic function of left ventricle[defined as cardiac contractility] was kept until 25 minutes of perfusion, but was decreased abruptly after 30 minutes of perfusion[p<0.0018] and diastolic function of left ventricle[defined as diastolic compliance] was kept until 15 minutes of perfusion, but was decreased after 20 minutes of perfusion [p=0.00\ulcorner9]. This study demonstrated maximal time of the tolerance to normothermic global ischemia and functional changes of left ventricle using Krebs perfusate under the same condition.

• 제어로봇시스템학회:학술대회논문집
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• 2001.10a
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• pp.55.4-55
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• 2001

Analyzing the ECG signal, we can find heart disease. Myocardial ischemia is a disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. Myocardial ischemia is inscribed on ST-segment of the ECG during and after patient takes exercise or is under stress, but after long time past, the ECG pattern is return to steady state. Therefore, it is necessary to monitor and analyze the ECG signal continuously for patient or aged people. Our primary purpose is the detection of temporary change of the ST-segment of ECG automatically. In the signal processing, the wavelet transform decomposes the ECG signal into high and low frequency components using wavelet function. Recomposing the high frequency bands including QRS complex, we can detect QRS complex more easily ...

• Proceedings of the KOSOMBE Conference
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• v.1997 no.11
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• pp.218-221
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• 1997

In this paper, we designed a myocaldial ischemia model based on L-R dynamic model including hyperkalemia and anoxia. Using the model, we simulated the effects of ionic concentration $[K^+]_o$ and intracellular $[ATP]_i$ on action potential in single cardiac cell. Also we evaluated this model by comparing the simulated results with that of other researches. In luther research, we are going to consider the effect of acidosis quantitatively.

• Journal of Chest Surgery
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• v.25 no.12
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• pp.1391-1398
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• 1992

The hypothesis tested is that shifts in pH, induced when a cardioplegic solution is oxygenated, can be detrimental. The object of this study is to evaluate the effect of the pH of the oxygenating cardioplegic solution on postischemic recovery in the isolated rat heart. Either 100% oxygen or 95% oxygen: 5% carbon dioxide was added to the cardioplegic solution[St. Thomas` Hospital No. 2] and determined postischemic recovery of isolated rat hearts after 2 hours and 3 hours of 20oC cardioplegic protected ischemia. Heart were arrested and reinfused every 30 minutes throughout the ischemic period with cardioplegic solution. When 100% oxygen was added, the pH of the cardioplegic solution increased from 7.8[no oxygen] to 8.5[100% oxygen] without any change in postischemic functional recovery. But when 95% oxygen ; 5% carbon dioxide was added, the pH of the cardioplegic solution reversely decreased to 6.84 in the 2-hour ischemic group and 6.73 in the 3-hour ischemic group, associated with improved postischemic functional recovery. After 2-hour ischemia, systolic pressure improved from 88.2$\pm$3.7%[no oxygen] and 88.7$\pm$3.8%[100% oxygen] to 96.6$\pm$1.8%[95% oxygen : 5% carbon dioxide], p<0.05, aortic flow from 43.3$\pm$3.1% and 38.4$\pm$10.6% to 74.5$\pm$5.0%, p<0.001, cardiac output from 55.5$\pm$4.6% and 47.4%$\pm$10.6% to 73.1$\pm$4.6%, p<0.05, stroke volume from 62.7$\pm$4.6% and 52.0$\pm$10.1% to 77.2$\pm$4.6%, p<0.05, and dP/dT from 59.3$\pm$7.2% and 56.7$\pm$7.6% to 78.9$\pm$4.6%, p<0.05. The infused amount of the cardioplegic solution during 2-hour ischemic period was similar in three groups. After 3-hour ischemia, cardiac output improved from 17.0$\pm$3.8%[no oxygen] to 45.9$\pm$7.5%[95% oxygen: 5% carbon dioxide], p<0.05, and stroke volume from 21.0$\pm$3.9%[no oxygen] to 50.1$\pm$6.6%[95% oxygen: 5% carbon dioxide], p<0.01. In conclusion, the St. Thomas` Hospital No. 2 cardioplegic solution should be oxygenated but with 95% oxygen: 5% carbon dioxide and not 100% oxygen because of the additive effect of a relatively "Acidotic" pH.t; pH.

• Journal of Chest Surgery
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• v.36 no.4
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• pp.242-254
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• 2003

Most of the studies conducted have investigated the beneficial effects of ischemic preconditioning on normothermic myocardial ischemia. However, the effect of preconditioning could be attenuated through the use of multidose cold cardioplegia as practiced in contemporary clinical heart surgical procedures. The purpose of this study was to investigate whether preconditioning improves postischemic cardiac function in a model of 25℃ moderate hypothermic ischemic heart induced by cold cardioplegia in isolated rat hearts. Material and Method: The isolated Sprague-Dawley rat hearts were randomly assigned to four groups. All hearts were perfused at 37℃ for 20 minutes with Krebs-Henseleit solution before the baseline hemodynamic data were obtained. Group 1 consisted of preconditioned hearts that received 3 minutes of global ischemic preconditioning at 37℃, followed by 5 minutes of reperfusion before 120 minutes of cardioplegic arrest (n=6). Cold (4℃) St. Thomas Hospital cardioplegia solution was infused to induce cardioplegic arrest. Maintaining the heart at 25℃, infusion of the cardioplegia solution was repeated every 20 minutes throughout the 120 minutes of ischemic period. Group 2 consisted of control hearts that underwent no manipulations between the periods of equilibrium and 120 minutes of cardioplegic arrest (n=6). After 2 hours of cardioplegic arrest, Krebs solution was infused and hemodynamic data were obtained for 30 minutes (group 1, 2: cold cardioplegia group). Group 3 received two episodes of ischemic preconditioning before 30 min of 37℃ normothermic ischemia and 30 minutes of reperfusion (n=6). Group 4 served as ischemic controls for group 3 (group 3, 4: warm ischemia group). Result: Preconditioning did not influence parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), rate-pressure product (RPP) and left ventricular dp/dt (LV dp/dt) in the cold cardioplegia group. (p=NS) However, preconditioning before warm ischemia attenuated the ischemia induced cardiac dysfunction, improving the LVSP, LVEDP, RPP, and LVdp/dt. Less leakage of CPK and LDH were observed in the ischemic preconditioning group compared to the control group (p<0.05). Conclusion: Ischemic preconditioning improved postischemic cardiac function after warm ischemia, but did not protect cold cardioplegic hearts.