• The Korean Journal of Physiology and Pharmacology
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• v.27 no.2
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• pp.143-155
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• 2023

Percutaneous coronary intervention and acute coronary syndrome are both closely tied to the frequently occurring complication of coronary microembolization (CME). Resveratrol (RES) has been shown to have a substantial cardioprotective influence in a variety of cardiac diseases, though its function and potential mechanistic involvement in CME are still unclear. The forty Sprague-Dawley rats were divided into four groups randomly: CME, CME + RES (25 mg/kg), CME + RES (50 mg/kg), and sham (10 rats per group). The CME model was developed. Echocardiography, levels of myocardial injury markers in the serum, and histopathology of the myocardium were used to assess the function of the cardiac muscle. For the detection of the signaling of TLR4/MyD88/NF-κB along with the expression of pyroptosis-related molecules, ELISA, qRT-PCR, immunofluorescence, and Western blotting were used, among other techniques. The findings revealed that myocardial injury and pyroptosis occurred in the myocardium following CME, with a decreased function of cardiac, increased levels of serum myocardial injury markers, increased area of microinfarct, as well as a rise in the expression levels of pyroptosis-related molecules. In addition to this, pretreatment with resveratrol reduced the severity of myocardial injury after CME by improving cardiac dysfunction, decreasing serum myocardial injury markers, decreasing microinfarct area, and decreasing cardiomyocyte pyroptosis, primarily by blocking the signaling of TLR4/MyD88/NF-κB and also reducing the NLRP3 inflammasome activation. Resveratrol may be able to alleviate CME-induced myocardial pyroptosis and cardiac dysfunction by impeding the activation of NLRP3 inflammasome and the signaling pathway of TLR4/MyD88/NF-κB.

• Journal of Chest Surgery
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• v.47 no.3
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• pp.233-239
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• 2014

Background: As hypertrophied myocardium predisposes the patient to decreased tolerance to ischemia and increased reperfusion injury, myocardial protection is of utmost importance in patients undergoing aortic valve replacement (AVR) for severe aortic valve stenosis (AS). Methods: Consecutive 314 patients (mean age, $62.5{\pm}10.8$ years; 143 females) with severe AS undergoing isolated AVR were included. Postoperative myocardial injury (PMI) was defined as 1) maximum postoperative creatinine kinase isoenzyme MB or troponin-I levels ${\geq}10$ times of reference, 2) postoperative low cardiac output syndrome or episodes of ventricular arrhythmia, or 3) left ventricular ejection fraction of less than 55% and decrease in left ventricle (LV) ejection fraction of more than 20% of the baseline value. Results: There were 90 patients (28.7%) who developed PMI. There were five cases of early death (1.6%), all of whom had PMI. On multivariable analysis, the use of histidine-tryptophan-ketoglutarate (HTK) solution instead of blood cardioplegia (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.63 to 5.77; p=0.001), greater LV mass (OR, 1.04; 95% CI, 1.01 to 1.07; p=0.007), and increased cardiac ischemic time (OR, 1.13; 95% CI, 1.05 to 1.22; p<0.001) were independent predictors for PMI. Patients who had PMI showed significantly inferior long-term survival than those without PMI (p=0.049). Conclusion: PMI occurred in a considerable proportion of patients undergoing AVR for severe AS and was associated with poor long-term survival. HTK cardioplegia, higher LV mass, and longer cardiac ischemic duration were suggested as predictors of myocardial injury.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.273-282
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• 2013

The present study was designed to investigate the cardioprotective effects of Korean Red Ginseng extract (KRG) on isoproterenol (ISO)-induced cardiac injury in rats, particularly in regards to electrocardiographic changes, hemodynamics, cardiac function, serum cardiac enzymes, components of the myocardial antioxidant defense system, as well as inflammatory markers and histopathological changes in heart tissue. ISO (150 mg/kg, subcutaneous, two doses administered at 24-hour intervals) treatment induced significant decreases in P waves and QRS complexes (p<0.01), as well as a significant increase in ST segments. Moreover, ISO-treated rats exhibited decreases in left-ventricular systolic pressure, maximal rate of developed left ventricular pressure ($+dP/dt_{max}$) and minimal rate of developed left ventricular pressure ($-dP/dt_{max}$), in addition to significant increases in lactate dehydrogenase, aspartate transaminase, alanine transaminase and creatine kinase activity. Heart rate, however, was not significantly altered. And the activities of superoxide dismutase, catalase and glutathione peroxidase were decreased, whereas the activity of malondialdehyde was increased in the ISO-treated group. ISO-treated group also showed increased caspase-3 level, release of inflammatory markers and neutrophil infiltration in heart tissue. KRG pretreatment (250 and 500 mg/kg, respectively) significantly ameliorated almost all of the parameters of heart failure and myocardial injury induced by ISO. The protective effect of KRG on ISO-induced cardiac injury was further confirmed by histopathological study. In this regard, ISO treatment induced fewer morphological changes in rats pretreated with 250 or 500 mg/kg of KRG. Compared with the control group, all indexes in rats administered KRG (500 mg/kg) alone were unaltered (p>0.05). Our results suggest that KRG significantly protects against cardiac injury and ISO-induced cardiac infarction by bolstering antioxidant action in myocardial tissue.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.67-72
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• 2014

To investigate the alteration of c-Jun N-terminal kinase (JNK) activity after myocardial ischemia reperfusion injury (MIRI) and further explore the effect of naloxone postconditioning on MIRI. Forty male Sprague Dawley rats were randomly divided into five groups: sham operation (sham, n=8); ischemia reperfusion (IR, n=8); IR+naloxone 0.5 mg/kg (Nal L, n=8); IR+naloxone 1.0 mg/kg (Nal M, n=8); IR+naloxone 2.0 mg/kg (Nal H, n=8). Pathological changes of myocardial tissue were visualized by HE staining. The expression of p-JNK, and the apoptosis of cardiomyocytes were investigated with Western blotting and the TUNEL assay, respectively. Irregular arrangement and aberrant structure of myocardial fibers, cardiomyocytes with granular or vacuolar degeneration, and inflammatory cells infiltrating the myocardial interstitial regions characterized MIRI in the IR group. Signs of myocardial injury and inflammatory infiltration were less prominent in the Nal-treated groups. The expression of p-JNK in the sham group and in all Nal-treated groups was significantly lower than that in the IR group (p<0.01). The apoptosis index of cardiomyocytes in the IR group was significantly higher than in the sham group (p<0.01). The apoptosis indices of cardiomyocytes in all Nal-treated groups were significantly reduced to 55.4%, 26.2%, and 27.6%, respectively, of the IR group (p<0.01). This study revealed that Naloxone postconditioning before reperfusion inhibits p-JNK expression and decreases cell apoptosis, thus alleviating MIRI.

• Nutrition Research and Practice
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• v.13 no.3
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• pp.205-213
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• 2019

BACKGROUND/OBJECTIVES: Myocardial infarction (MI) is caused by extensive myocardial damage attributed to the occlusion of coronary arteries. Our previous study in a rat model of ischemia/reperfusion (I/R) demonstrated that administration of arabinoxylan (AX), comprising arabinose and xylose, protects against myocardial injury. In this study, we undertook to investigate whether psyllium seed husk (PSH), a safe dietary fiber containing a high level of AX (> 50%), also imparts protection against myocardial injury in the same rat model. MATERIALS/METHODS: Rats were fed diets supplemented with PSH (1, 10, or 100 mg/kg/d) for 3 d. The rats were then subjected to 30 min ischemia through ligation of the left anterior descending coronary artery, followed by 3 h reperfusion through release of the ligation. The hearts were harvested and cut into four slices. To assess infarct size (IS), an index representing heart damage, the slices were stained with 2,3,5-triphenyltetrazolium chloride (TTC). To elucidate underlying mechanisms, Western blotting was performed for the slices. RESULTS: Supplementation with 10 or 100 mg/kg/d of PSH significantly reduces the IS. PSH supplementation (100 mg/kg/d) tends to reduce caspase-3 generation and increase BCL-2/BAX ratio. PSH supplementation also upregulates the expression of nuclear factor erythroid 2-related factor 2 (NRF2), and its target genes including antioxidant enzymes such as glutathione S-transferase mu 2 (GSTM2) and superoxide dismutase 2 (SOD2). PSH supplementation upregulates some sirtuins ($NAD^+$-dependent deacetylases) including SIRT5 (a mitochondrial sirtuin) and SIRT6 and SIRT7 (nuclear sirtuins). Finally, PSH supplementation upregulates the expression of protein kinase A (PKA), and increases phosphorylated cAMP response element-binding protein (CREB) (pCREB), a target protein of PKA. CONCLUSIONS: The results from this study indicate that PSH consumption reduces myocardial I/R injury in rats by inhibiting the apoptotic cascades through modulation of gene expression of several genes located upstream of apoptosis. Therefore, we believe that PSH can be developed as a functional food that would be beneficial in the prevention of MI.

• 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.

• Journal of Chest Surgery
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• v.23 no.1
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• pp.9-15
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• 1990

This study was designed to investigate the protective effect of chlorpromazine against the reperfusion injury of myocardium after high potassium cardioplegic arrest. Langendorff`s preparations of rat heart were infused with high potassium cardioplegic solution[St. Thomas Hospital Solution] at 25oC. Chlorpromazine [10-7Ｍ] increased the recovery of myocardial contractility[dp/dt], left ventricular pressure[LVP], and coronary flow rate of the reperfused heart. Both in control and experimental groups, the restoration of myocardial activity could not reach to the level of preplegic control. These results suggest that the etiologic factors of the reperfusion injury include the influence of high potassium cardioplegic solution and/or reperfusion itself, and that chlorpromazine protects myocardium from the reperfusion injury.

• Clinical and Experimental Pediatrics
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• v.45 no.2
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• pp.208-213
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• 2002

Purpose : The major cause of cardiac dysfunction, after open heart surgery for congenital heart disease, is perioperative myocardial injury. Cardiac troponin I is found only within the myocardial cell, so it can be used as a biochemical marker of the myocardial injury. We performed this study to evaluate the worth of cardiac troponin I as a biochemical marker reflecting the extent of perioperative myocardial injury and recovery. Methods : Thirty-four patients who had undergone elective open heart surgery of congenital heart disease(CHD) from April to July 2001 were enrolled in this study. We measured types of CHD, serial cardiac troponin I(baseline 1 day before operation, postoperative day 1, 2, 3, 7), duration of cardiopulmonary bypass(CPB), aortic cross clamping(ACC), intubation and postoperative hospital stay. Results : Compared with the baseline before operation, there was a significant, increase of cardiac troponin I on the postoperative day 1 and a significant gradual decrease on the day 2, 3, 7. The levels of cardiac troponin I were the highest in the transposition of great artery(TGA) repair on the postoperative day 1 and high in the tetralogy of Fallot(TOF), atioventricular septal defect (AVSD), ventricular septal defect(VSD) and atrial septal defect(ASD) repair with decreasing sequence. The longer duration of CPB, ACC and intubation, the higher of cardiac troponin I, but there were no significant correlations between cardiac troponin I levels and duration of hospital stay. Conclusion : Because there was significant increases or decreases of cardiac troponin I according to the perioperative time and types of the congenital heart disease, it is a worthy biochemical marker which reflects the extent of perioperative myocardial injury and recovery after open heart surgery.

• The Korea Journal of Herbology
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• v.26 no.4
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• pp.149-154
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• 2011

Objectives : Myocardial infarction is caused by heart cell death in a region where coronary arteries supplying blood to the region are occluded. In the present study, we determined whether ethanol extract of Cortex fraxini (HY5053) could attenuate heart injury by inhibiting apoptosis. Methods : Improvement of survival of HepG2 cells, a human hepatocellular carcinoma cell line, and reduction of apoptosis under hypoxic conditions (3% $O_2$) were assessed by trypan blue staining and DNA fragmentation assay, respectively. To assess the impact of HY5053 on the heart injury, Sprague-Dawley rats underwent 1 day of the left anterior descending coronary artery occlusion. HY5053 was given by intraperitoneal injection (200 mg/kg) 1 hr prior to the occlusion. Subsequently, the heart were harvested, excised into 4 slices, and the slices were stained with 2,3,5-triphenyl tetrazolium chloride. Finally, the extent of heart injury represented as ischemic index (%) was assessed. Results : Addition of HY5053 (400 ${\mu}g$/mL) into the culture medium for 1 day under ischemic conditions improved the cell survival by 50%, compared with control (0 ${\mu}g$/mL), consequently delayed apoptosis in 6 hr difference. Also, HY5053 (200 mg/kg) reduced the ischemic index by 44%, compared with control (0 mg/kg). Conclusions : These findings suggested that HY5053 attenuated myocardial infarction by inhibiting apoptosis. Thus, Cortex fraxini could be developed as a novel cardioprotectant to complement a currently available treatment, coronary angioplasty.

• 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.