• Journal of Chest Surgery
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• v.17 no.4
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• pp.565-573
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• 1984

The increasing use of cardioplegic solution for the reduction of ischemic tissue injury requires that all cardioplegic solution be carefully assessed for any protective or damaging properties. This study describes functional assessment of the efficiency of steroid in cardioplegic solution by using a Langendorffs perfusion model. Isolated rat heart were subject to a 2 minute period of coronary infusion with the steroid mixed cold cardioplegic solution immediately before and also at the midpoint of a 60 minutes period of hypothermic [10\ulcorner\ulcorner] ischemic arrest. The result of this study were as follows: 1.Spontaneous heart beat after ischemic arrest occurred 14 second later Langendorffs reperfusion in the steroid mixed Young & GIK group and 16 second later in the control group. [Young & GIK without steroid] A good recovery state of spontaneous heart beat was shown in both groups. 2.The percentage of recoveries of heart rate during the 30 minute after postischemic Langendorffs reperfusion was; at first 5 minute 106.3\ulcorner.7% [P<0.05] in the steroid mixed Young & GIK group. This percentage of recovery of steroid mixed Young & GIK group was significantly greater than the control group during the first 5 minute course. 3.The percentage of recovery of coronary flow during the 30 minute after postischemic Langendorffs reperfusion was; at first 5 minute 101\ulcorner.2% in the steroid mixed Young & GI K group. This percentage of recovery of the steroid mixed Young & GIK group was not significantly than the control group during the first 5 minute.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.281-296
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• 2021

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O₂ for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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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.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.5
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• pp.325-333
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• 2022

Heart failure (HF) has become one of the severe public health problems. The detailed role of mitochondrial function in HF was still unclear. Benzoylaconine (BAC) is a traditional Chinese medicine, but its role in HF still needs to be explored. In this study, oxygen-glucose deprivation and reperfusion (OGD/R) was executed to mimic the injury of H9C2 cells in HF. The viability of H9C2 cells was assessed via MTT assay. OGD/R treatment markedly decreased the viability of H9C2 cells, but BAC treatment evidently increased the viability of OGD/R-treated H9C2 cells. The apoptosis of H9C2 was enhanced by OGD/R treatment but suppressed by BAC treatment. The mitochondrial membrane potential was evaluated via JC-1 assay. BAC improved the mitochondrial function and suppressed oxidative stress in OGD/R-treated H9C2 cells. Moreover, Western blot analysis revealed that the protein expression of p-AMPK and PGC-1α were reduced in OGD/R-treated H9C2 cells, which was reversed by BAC. Rescue assays indicated that AMPK attenuation reversed the BAC-mediated protective effect on OGD/R-treated cardiomyocytes. Moreover, BAC alleviated myocardial injury in vivo. In a word, BAC modulated the mitochondrial function in OGD/R-induced cardiomyocyte injury by activation of the AMPK/PGC-1 axis. The findings might provide support for the application of BAC in the treatment of HF.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.321-330
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• 1994

The protective effect of 'ischemic preconditioning (PC)' on ischemia-reperfusion injury of heart has been reported in various animal species, but without known mechanisms in detail. In an attempt to investigate the cardioprotective mechanism of PC, we examined the effects of PC on the myocardial oxidative injuries and the oxygen free radical production in the ischemia-reperfusion model of isolated Langendorff preparations of rat hearts. PC was performed with three episodes of 5 min ischemia and 5 min reperfusion before the induction of prolonged ischemia (30 min)-reperfusion(20 min). PC prevented the depression of cardiac function (left ventricular pressure x heart rate) observed in the ischemic-reperfused heart, and reduced the release of lactate dehydrogenase during the reperfusion period. On electron microscopic pictures, myocardial ultrastructures were relatively well preserved in PC hearts as compared with non-PC ischemic-reperfused hearts. In PC hearts, lipid peroxidation of myocardial tissue as estimated from malondialdehyde production was markedly reduced. PC did not affect the activity of xanthine oxidase which is a major source of oxygen radicals in the ischemic rat hearts, but the myocardial content of hypoxanthine (a substrate for xanthine oxidase) was much lower in PC hearts. It is suggested from these results that PC brings about significant myocardial protection in ischemic-reperfused heart and this effect may be related to the suppression of oxygen free radical reactions.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.31-37
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• 1996

The protective effect of 'ischemic preconditioning (IP)'on ischemia-reperfusion injury of heart has been reported in various animal species, but the mechanism is unclear. In an attempt to elucidate the mechanism of IP, we examined the effects of blockers against adenosine and protein kinase C in preconditioned heart of rat. The hearts perfused with oxygen-saturated Krebs-Henseleit solution by Langendorff method were exposed to 30 min global ischemia followed by 20 min reperfusion. IP was performed with three episodes of 5 min ischcmia and 5 min reperfusion just before ischemia-reperfusion. IP prevented the depression of contractile function and the myocardial contracture in the ischemic-reperfused heart and reduced the release of lactate dehydrogenase during the reperfusion period. Polymyxin B, chelerythrine and colchicine, PKC inhibitors, attenuated almost completely the anti-ischemic effect of IP, while adenosine receptor antagonists did not. These results indicate that PKC may be a crucial intracellular mediator in anti-ischemic action of IP in ischemic-reperfused rat heart, while adenosine may not be involved in the mechanism of IP.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.283-292
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• 2013

Ginsenosides are divided into two groups based on the types of the panaxadiol group (e.g., ginsenoside-Rb1 and -Rc) and the panaxatriol group (e.g., ginsenoside-Rg1 and -Re). Among them, ginsenoside-Re (G-Re) is one of the compounds with the highest content in Panax ginseng and is responsible for pharmacological effects. However, it is not yet well reported if G-Re increases the hemodynamics functions on ischemia (30 min)/reperfusion (120 min) (I/R) induction. Therefore, in the present study, we investigated whether treatment of G-Re facilitated the recovery of hemodynamic parameters (heart rate, perfusion pressure, aortic flow, coronary flow, and cardiac output) and left ventricular developed pressure (${\pm}dp/dt_{max}$). This research is designed to study the effects of G-Re by studying electrocardiographic changes such as QRS interval, QT interval and R-R interval, and inflammatory marker such as tissue necrosis factor-${\alpha}$ (TNF-${\alpha}$) in heart tissue in I/R-induced heart. From the results, I/R induction gave a significant increase in QRS interval, QT interval and R-R interval, but showed decrease in all hemodynamic parameters. I/R induction resulted in increased TNF-${\alpha}$ level. Treatment of G-Re at 30 and $100{\mu}M$ doses before I/R induction significantly prevented the decrease in hemodynamic parameters, ameliorated the electrocardiographic abnormality, and inhibited TNF-${\alpha}$ level. In this study, G-Re at $100{\mu}M$ dose exerted more beneficial effects on cardiac function and preservation of myocardium in I/R injury than $30{\mu}M$. Collectively, these results indicate that G-Re has distinct cardioprotectective effects in I/R induced rat heart.

• Journal of radiological science and technology
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• v.24 no.2
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• pp.19-22
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• 2001

The purpose of this study is to evaluate time course of signal enhancement on Gadomer-17 enhance MRI, and to correlate the size of enhanced area with that of the infarct area on 2'3'5'-triphenyl tetrazolium chloride(TTC) histochemical examination for the assessment of myocardial viability in reperfused Myocardial Infarction in a cat model. Tan cats(average weight: 3.8 kg) which had undergone 90 minutes of occlusion of the LAD followed by 90 minutes of reperfusion underwent MR T2-weighted imaging, and T1-weighted imaging, enhanced T1-weighted imaging. We used 1.5T Magneton Vision MRI system(Siemens, Erlangen, Germany). Signal intensities were measured in the enhanced and non-enhanced areas of enhanced T1-weighted imaging. and TTC histochemical staining the size of the abnormal signal area on each image was compared with that of the infarct area. Maximum enhancement was detected during a $40{\sim}60$ minute period with an average enhancement of $168{\pm}9.9%$ of normal myocardium. TTC staining revealed that the size of the high signal area on T2-weighted images and of the enhanced area on enhanced T1-weighted images was greater than that of the infarct area($T2=48.1%{\pm}3.7$, enhanced $T1=47.2%{\pm}2.6$, TTC $staining=38.7%{\pm}3.1$ ; p<0.05). In reperfused Myocardial Infarction in a cat model, enhanced MR imaging delineates reversibly and irreversibly damaged myocardium, with a strong enhancement and a broad temporal window. We may therefore expect that enhanced MR image is useful for demonstrating myocardial injury.

• Journal of Chest Surgery
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• v.27 no.7
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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.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.7-12
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• 1990

Cyclobuxine D is a steroidal alkaloid, which was extracted from Buxus microphylla var. koreana Nakai. In our previous studies, we clarified several pharmacological actions of cyclobuxine D: an antiinflammatory action, hypotensive and bradycardiac effects, negative inotropic effects on the several smooth muscles and cardiac muscle. The present study was undertaken to elucidate possible mechanisms by protection of myocardial tells from ischemia and reperfusion induced derangement in cardiac function and metabolism by cyclobuxine D. For this purpose, the isolated rat heart was used. Rat hearts were perfused for 60 min under ischemia conditions in the presence and absence of cyclobuxine D and verapamil, and for 30 min under reperfusion conditions. Ischemia produced a marked decline in contractile force, an increase of resting tension, an immediate release of ATP metabolites and an accumulation of calcium in the left ventricle. Cyclobuxine D (100ng/ml) ameliorated the myocardial injury produced by ischemia.