• Toxicological Research
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• v.11 no.1
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• pp.161-168
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• 1995

It has been found that various stress challenges induce the myocardial antioxidant enzymes and produce an acquisition of the cellular resistance to the ischemic injury in animal hearts. Most of the stresses, however, seem to be guite dangerous to an animal's life. In the present study, therefore, we tried to search for safely applicable stress modalities which could lead to the induction of antioxidant enzymes and the production of myocardial tolerance to the ischemia-reperfusion injury. Male Sprague-Dawley rats (200-250 g) were exposed to various non-fatal stress conditions, i.e., hyperthermia (environmental temperature of $42^{\circ}C$ for 30 min, non-anesthetized animal), iramobilization (60 min), treadmill exercise (20 m/min, 30min), swimming (30 min), and hyperbaric oxyflenation (3 atm, 60 min), once a day for 5 days. The activities of myocardial antioxidant enzymes and the ischemia-reperfusion injury of isolated hearts were evaluated at 24 hr after the last application of the stresses. The activities of antioxidant enzymes, superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase (G6PD), were assayed in the freshly excised ventricular tissues. The ischemia-reperfusion injury was produced by 20 min-global ischemia followed by 30 min-reperfusion using a Langendorff perfusion system. In swimming and hyperbaric oxygenation groups, the activities of SOD and G6PD increased significantly and in the hyperthermia group, the catalase activity was elevated by 63% compared to the control. The percentile recoveries of cardiac function at 30 min of the post-ischemic reperfusion were 55.4%, 73.4%, and 74.2% in swimming, the hyperbaric oxygenation and the hyperthermia groups, respectively. The values were significantly higher than that of the control (38.6%). In additions, left ventricular end-diastolic pressure and lactate dehydrogenase release were significantly reduced in the stress groups. The results suggest that the antioxidant enzymes in the heart could be induced by the apparently safe in vivo-stresses and this may be involved in the myocardial protection from the ischemia-reperfusion injury.

• Preventive Nutrition and Food Science
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• v.17 no.3
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• pp.177-183
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• 2012

Interruption of blood flow through coronary arteries and its subsequent restoration triggers the generation of a burst of reactive oxygen species (ROS), leading to myocardial cell death. In this study, we determined whether a methanol extract of Cassia mimosoides var. nomame Makino could prevent myocardial ischemia-reperfusion injury. When radical scavenging activity of the extract was measured in vitro using its ${\alpha}$,${\alpha}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH) radical quenching ability, the extract showed an activity slightly lower than that of ascorbic acid. Three days after oral administration of the extract (400 mg/kg/day) to rats, myocardial ischemia/reperfusion injury was generated by 30 min of ligation of the left anterior descending coronary artery (LAD), followed by 3 hr reperfusion. Compared with the vehicle-treated group, administration of the extract significantly reduced infarct size (IS) (ratio of infarct area to area at risk) in the extract-treated group by 28.3%. Reduction in the cellular injury was mediated by attenuation of Bax/Bcl-2 ratio by 33.3%, inhibition of caspase-3 activation from procaspase-3 by 40%, and subsequent reduction in the number of apoptotic cells by 66.3%. These results suggest that the extract attenuates myocardial injury in a rat model of ischemia-reperfusion by scavenging ROS, including free radicals, and consequently blocking apoptotic cascades. Therefore, intake of Cassia mimosoides var. nomame Makino might be beneficial for preventing ischemic myocardial injury.

• 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.

• 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.

• 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.

• 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.

• Molecules and Cells
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• v.40 no.12
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• pp.916-924
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• 2017

MicroRNAs are widely involved in the pathogenesis of cardiovascular diseases through regulating gene expression via translational inhibition or degradation of their target mRNAs. Recent studies have indicated a critical role of microRNA-206 in myocardial ischaemia-reperfusion (I/R) injury. However, the function of miR-206 in myocardial I/R injury is currently unclear. The present study was aimed to identify the specific role of miR-206 in myocardial I/R injury and explore the underlying molecular mechanism. Our results revealed that the expression level of miR-206 was significantly decreased both in rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation (H/R) compared with the corresponding control. Overexpression of miR-206 observably decreased infarct size and inhibited the cardiomyocyte apoptosis induced by I/R injury. Furthermore, bioinformatics analysis, luciferase activity and western blot assay proved that $Gadd45{\beta}$ (growth arrest DNA damage-inducible gene $45{\beta}$) was a direct target gene of miR-206. In addition, the expression of pro-apoptotic-related genes, such as p53, Bax and cleaved caspase3, was decreased in association with the down-regulation of $Gadd45{\beta}$. In summary, this study demonstrates that miR-206 could protect against myocardial I/R injury by targeting $Gadd45{\beta}$.

• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.46-54
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• 2000

Objectives : Talmyung-san(TMS) has been used for treatment of brain diseases in Chinese traditional medicine. However, little is known about the mechanism by which TMS rescues brain cells from ischemic damages. To elucidate the protective mechanisms of TMS, we execute experiments. Methods : The effects of TMS on ischemia/reperfusion-induced cytotoxicity and generation of nitric oxide(NO) are investigated in primary neonatal myocardial cells and A7rS, aortic smooth muscle cell line. Results : Ischemia/reperfusion itself induces severe myocardial cell death in vitro. However, treatment of the cells with TMS significantly reduces both ischemia/reperfusion-induced myocardial cell death and LDH release. In addition, pretreatment of TMS before reperfusion recovers the lose of beating rates alter ischemia/reperfusion. For a while, the water extract of TMS stimulates myocardial cells to produce NO in a dose dependent manner and it protects the damage of ischemia/reperfusion-induced myocardial cells. Furthermore, the protective effects of the water extract of TMS is mimicked by treatment of sodium nitroprusside, an exogenous NO donor. NG-monomethyl-L-arginine (NGMMA), a specific inhibitor of nitric oxide synthase(NOS), significantly blocks the protective effects of TMS on the cells after ischemia/reperfusion. In addition, on ischemia the water extract of TMS induce NO in A7r5 cell. Conclusions : Taken together, we suggest that the protective effects of TMS against ischemia/reperfusion-induced myocardial damages may be mediated by NO production of myocardial and vascular smooth muscle cell during ischemic condition.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.358-363
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• 1998

Intravenous lipid emulsion is used extensively as a major component of parenteral nutrition for patients in the surgical intensive care unit. Abnormal cardiovascular function related to lipid infusion has been reported although conflicting results exist. In the present study, we investigated the effects of intravenous emulsions of long-chain triglyceride (LCT) and medium-chain triglyceride (MCT) on myocardial ischemia/ reperfusion injury and on platelet aggregation in rat. There was no difference between LCT and MCT considering the effects on left ventricular developed pressure (LVDP) and coronary flow rate (CFR) before and after ischemia/reperfusion in isolated rat heart. On the other hand, a difference was found between LCT and MCT with regard to their effects on heart rate (HR) and end diastolic pressure (EDP) after ischemia/reperfusion. After ischemia/reperfusion, HR was significantly (P<0.05) reduced and EDP significantly (P<0.05) inc.eased by LCT (18$\pm$2.0% and 42.8$\pm$8.9%, respectively), but not by MCT Ex vivo platelet aggregation induced by collagen was reduced by LCT infusion, but not by MCT These findings suggest that MCT may have slightly more favorable effect than LCT on the myocardial function after ischemia/reperfusion in rat.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.749-758
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• 1997

Myocardial ischemia-reperfusion injury is known to be mediated by reactive oxygen species. The myocardial cell is equipped with endogenous antioxidant defensive system which can be adaptively stimulated by various oxidative stress. It is postulated that an increased oxygen partial pressure induced by hyperbaric oxygenation impose an oxidative stress on the cells, resulting alterations in the endogenous antioxidant system. In this study we investigated the effect of hyperbaric oxygenation on the activities of myocardial antioxidant enzymes and observed whether the hyperbaric oxygenation could protect the ischemia-reperfusion injury of heart. Rats or rabbits were pretreated with hyperbaric $oxygenation(2{\sim}3\;atm\;O_2/1{\sim}3\;hrs/1{\sim}10\;days)$. The changes in activities of major antioxidant enzymes(superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phasphate dehydrogenase), functional recovery and infarct size were observed in the experimentally induced ischemia-reperfused hearts. In the hearts isolated from rats pretreated with $2\;atm\;O_2/1{\sim}2\;hrs$ for 5 days, the functional recovery after reperfusion(20 min) following global ischemia(25 min) was significantly increased without any observable oxygen toxicity. Lactate dehydrogenase release was also significantly reduced in this hyperbaric oxygenated rat hearts. In in vivo regional ischemia(30 min) model of rabbit hearts, pretreatrment with $2\;atm\;O_2/1\;hr$ for 5 days significantly limited the infarct size. Among the myocardial antioxidant enzymes of rat hearts pretreated with the hyperbaric oxygenation, the activities of catalase, superoxide dismutase and glucose-6-phosphatase dehydrogenase were increased, while those of glutathione peroxidase and reductase were not changed. There were lethal cases in the groups of rats exposed to 3 atm $3\;atm\;O_2/2{\sim}3\;hrs$ for 5 days. A lipid-peroxidation product, rnnlondialdehyde was increased in brains and livers of the rats exposed to$2\;atm\;O_2/2{\sim}3\;hrs/5\;days\;and\;3\;atm\;O_2/1\;hr/5days$. The present results suggest that the pretreatment of hyperbaric oxygenation can protect the post-ischemic rererfused hearts in association with a stimulation of the activities of myocardial antioxidant defensive enzymes, and that the hyperbaric oxygenation of $2\;atm\;O_2/1\;hr$for 5 days would be a safe condition which does not produce any oxygen toxicity.