• Journal of Korean Neurosurgical Society
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• v.39 no.4
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• pp.300-302
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• 2006

"Stunning" represents prolonged contractile depression of any muscular component after alleviation of severe ischemia, as shown in reperfusion following acute myocardial ischemia or ischemic stroke. Clinically, it presents with no or delayed recovery past to thrombolytic therapy but its pathogenic mechanism is not fully uncovered yet. We describe a unique case of a 63-year-old woman, who was undertaken endovascular coiling for the aneurysms, deteriorated several hours later without known cause, and showed delayed clinical improvement over the next 3 days following thrombolysis. Immediate post-thrombolysis magnetic resonance imaging scan showed no apparent abnormality except for high signal intensity within the corresponding hemisphere. Reversible but delayed nature of " brain stunning" can be explained by these images and it seems to be caused by a certain type of reperfusion injury.

• 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.

• Journal of Chest Surgery
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• v.32 no.11
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• pp.971-977
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• 1999

Background: Immunologic and inflammatory responses of cardiopulmonary bypass(CPB) influence postoperative mortality and morbidity with multiple organ injury. It has been reported that ischemia/reperfusion induced-myocardial injury during CPB is causative of release of inflammatory cytokines such as interleukin-6(IL-6) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$). The purpose of this study was to detect the time course of the activated cytokine and troponin-T(TnT), and to examine the correlation between such parameters during CPB. Material and Method: The serial samples were collected from arterial blood via radial arterial catheter in 23 patients who are underwent open heart surgery (OHS) with CPB, the IL-6, TNF-$\alpha$ and TnT were checked. Result: \circled1 IL-6, TNF$\alpha$- and TnT concentration increased significantly during CPB with a peaking level of CPB-off (p 0.05). \circled2 IL-6 had highly positive correlation with aortic cross clamping time and total bypass time(r=0.80, 0.78; p 0.05, respectively). \circled3 There was no correlation among IL-6, TNF-$\alpha$ and TnT. Conclusion: In conclusion, these data showed that elevated production of serum IL-6 during CPB was attributable to ischemia/reperfusion induced-myocardial damage. IL-6 will become a new and sensitive biological marker in assessment of myocardial damage during OHS with CPB. However, further studies will be needed to apply IL-6 in more patient population.

• 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.32 no.2
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• pp.201-209
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• 1996

Restoration of the blood flow after a period of ischemia is accompanied by generation of toxic oxygen radicals. This phenomenon may account for the occurrence of reperfusion-mediated tissue injury in ischemic hearts. In in vitro studies, although oxygen radicals can be generated from a variety of sources, including xanthine oxidase system, activated leucocytes, mitochondria and others, the most important source and mechanism of oxygen radical production in the post-ischemic reperfused hearts is unclear. In the present study, we tested the hypothesis that the respiratory chain of mitochondria might be an important source of oxygen radicals which are responsible for the development of the reperfusion injury of ischemic hearts. Langendorff-perfused, isolated rat hearts were subjected to 30 min of global ischemia at $37^{\circ}C$, followed by reperfusion. Amytal, a reversible inhibitor of mitochondrial respiration, was employed to assess the mitochondrial contributions to the development of the reperfusion injury. Intact mitochonria were isolated from the control and the post-ischemic reperfused hearts. Mitochondrial oxygen radical generation was measured by chemiluminescence method and the oxidative tissue damage was estimated by measuring a lipid peroxidation product, malondialdehyde(MDA). To evaluate the extent of the reperfusion injury, post-ischemic functional recovery and lactate dehydrogenase(LDH) release were assessed and compared in Amytal-treated and -untreated hearts. Upon reperfusion of the ischemic hearts, MDA release into the coronary effluent was markedly increased. MDA content of mitochondria isolated from the post-ischemic reperfused hearts was increased to 152% of preischemic value, whereas minimal change was observed in extramitochondrial fraction. The generation of superoxide anion was increased about twice in mitochondria from the reperfused hearts than in those from the control hearts. Amytal inhibited the mitochondrial superoxide generation significantly and also suppressed MDA production in the reperfused hearts. Additionally, Amytal prevented the contractile dysfunction and the increased release of LDH observed in the reperfused hearts. In conclusion, these results indicate that the respiratory chain of mitochondria may be an important source of oxygen radical formation in post-ischemic reperfused hearts, and that oxygen radicals originating from the mitochondria may contribute to the development of myocardial reperfusion injury.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.239-249
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• 2021

The present study explored the therapeutic potential of hydrogen sulfide (H2S) in restoring aging-induced loss of cardioprotective effect of remote ischemic preconditioning (RIPC) along with the involvement of signaling pathways. The left hind limb was subjected to four short cycles of ischemia and reperfusion (IR) in young and aged male rats to induce RIPC. The hearts were subjected to IR injury on the Langendorff apparatus after 24 h of RIPC. The measurement of lactate dehydrogenase, creatine kinase and cardiac troponin served to assess the myocardial injury. The levels of H2S, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), nuclear factor erythroid 2-related factor 2 (Nrf2), and hypoxia-inducible factor (HIF-1α) were also measured. There was a decrease in cardioprotection in RIPC-subjected old rats in comparison to young rats along with a reduction in the myocardial levels of H2S, CBS, CSE, HIF-1α, and nuclear: cytoplasmic Nrf2 ratio. Supplementation with sodium hydrogen sulfide (NaHS, an H2S donor) and l-cysteine (H2S precursor) restored the cardioprotective actions of RIPC in old hearts. It increased the levels of H2S, HIF-1α, and Nrf2 ratio without affecting CBS and CSE. YC-1 (HIF-1α antagonist) abolished the effects of NaHS and l-cysteine in RIPC-subjected old rats by decreasing the Nrf2 ratio and HIF-1α levels, without altering H2S. The late phase of cardioprotection of RIPC involves an increase in the activity of H2S biosynthetic enzymes, which increases the levels of H2S to upregulate HIF-1α and Nrf2. H2S has the potential to restore aging-induced loss of cardioprotective effects of RIPC by upregulating HIF-1α/Nrf2 signaling.

• Molecules and Cells
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• v.40 no.8
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• pp.542-549
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• 2017

Cardiomyocyte apoptosis is initiated by various cellular insults and accumulated cardiomyocyte apoptosis leads to the pathogenesis of heart failure. Excessive reactive oxygen species (ROS) provoke apoptotic cascades. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme that converts cellular ROS into harmless products. In this study, we demonstrate that MnSOD is down-regulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Enhanced expression of MnSOD attenuates cardiomyocyte apoptosis and myocardial infarction induced by I/R injury. Further, we show that miR-23a directly regulates the expression of MnSOD. miR-23a regulates cardiomyocyte apoptosis by suppressing the expression of MnSOD. Our study reveals a novel model regulating cardiomyocyte apoptosis which is composed of miR-23a and MnSOD. Our study provides a new method to tackling apoptosis related cardiac diseases.

• Journal of Chest Surgery
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• v.31 no.8
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• pp.739-748
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• 1998

Background: It has been well documented that transient occlusion of the coronary artery causes myocardial ischemia and finally cell death when ischemia is sustained for more than 20 minutes. Extensive studies have revealed that ischemic myocardium cannot recover without reperfusion by adequate restoration of blood flow, however, reperfusion can cause long-lasting cardiac dysfunction and aggravation of structural damage. The author therefore attempted to examine the effect of postischemic reperfusion on myocardial ultrastructure and to determine the rationales for recanalization therapy to salvage ischemic myocardium. Materials and methods: Young Holstein-Friesian cows(130∼140 Kg body weight; n=40) of both sexes, maintained with nutritionally balanced diet and under constant conditions, were used. The left anterior descending coronary artery(LAD) was occluded by ligation with 4-0 silk snare for 20 minutes and recanalized by release of the ligation under continuous intravenous drip anesthesia with sodium pentobarbital(0.15 mg/Kg/min). Drill biopsies of the risk area (antero-lateral wall) were performed at just on reperfusion(5 minutes), 1-, 2-, 3-, 6-, 12-hours after recanalization, and at 1-hour assist(only with mechanical respiration and fluid replacement) after 12-hour recanalization. The materials were subdivided into subepicardial and subendocardial tissues. Tissue samples were examined with a transmission electron microscope (Philips EM 300) at the accelerating voltage of 60 KeV. Results: After a 20-minute ligation of the LAD, myocytes showed slight to moderate degree of ultrastructural changes including subsarcolemmal bleb formation, loss of nuclear matrix, clumping of chromatin and margination, mitochondrial destruction, and contracture of sarcomeres. However, microvascular structures were relatively well preserved. After 1-hour reperfusion, nuclear and mitochondrial matrices reappeared and intravascular plugging by polymorphonuclear leukocytes or platelets was observed. However, nucleoli and intramitochondrial granules reappeared within 3 hours of reperfusion and a large number of myocytes were recovered progressively within 6 hours of reperfusion. Recovery was apparent in the subepicardial myocytes and there were no distinct changes in the ultrastructure except narrowed lumen of the microvessels in the later period of reperfusion. Conclusions: It is likely that the ischemic myocardium could not be salvaged without adequate restoration of coronary flow and that the microvasculature is more resistant to reversible period of ischemia than subendocardium and subepicardium. Therefore, thrombolysis and/or angioplasty may be a rational method of therapy for coronarogenic myocardial ischemia. However, it may take a relatively longer period of time to recover from ischemic insult and reperfusion injury should be considered.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.4
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• pp.319-324
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• 2000

The causal relationship between heat shock protein (HSP) and second window of cardioprotective effect is still undetermined. In the present study, we assessed whether HSP-producing substances, amphetamine and ketamine, afforded protection against reperfusion-induced ventricular fibrillation (VF) and these protective effect remained after the inhibition of HSP72 production by quercetin, a mitochondrial ATPase inhibitor. Adult mongreal male cats $(n=60,\;2.5{\sim}4\;kg)$ were used in this study. Experimental animals were divided into five groups; control group (n=15), amphetamine ('A', n=11) group, ketamine ('K', n=9) group, amphetamine-ketamine ('AK', n=16) group and amphetamine-ketamine-quercetin ('AKQ', n=9) group. Twenty-four hours after the drug treatment, an episode of 20-min coronary artery occlusion was followed by 10-min reperfusion. The incidence of reperfusion-induced VF in the AK and AKQ groups was significantly lower than that in control group (p＜0.01). After the ischemia/reperfusion procedure, western blot analysis of HSP72 expression in the myocardial tissues resected from each group was performed. HSP72 production in the AK group was marked, whereas HSP72 was not detected in the AKQ and control groups. These results suggest that the suppressive effect against reperfusion-induced VF induced by amphetamine and ketamine is not mediated by myocardial HSP72 production but by other mechanisms.

• 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.