• Journal of Ginseng Research
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• 제33권4호
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• pp.268-277
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• 2009

Ginsenosides are among the most well-known traditional herbal medicines frequently used for the treatment of cardiovascular symptoms in South Korea. The anti-ischemic effects of compound K (CK), a metabolite of ginsenoside Rb1, on ischemia-induced isolated rat hearts were investigated through the analyses of the changes in the hemodynamics (blood pressure, aortic flow, coronary flow, and cardiac output) and the measurement of the infarct region. The subjects in this study were divided into four groups: the normal control, the CK-alone group, the ischemia-induced group without any treatment, and the ischemia-induced group treated with CK. No significant differences in perfusion pressure, aortic flow, coronary flow, and cardiac output were found between the groups before ischemia was induced. The oxygen and buffer supply was stopped for 30 min to induce ischemia 60 min after reperfusion in the isolated rat hearts, and the CK was administered 5 min before ischemia induction. The CK treatment significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions. In addition, the hemodynamics (except for the heart rate) of the group treated with CK significantly recovered 60 min after reperfusion, unlike in the control group. CK significantly limited the infarct. These results suggest that CK treatment has distinct anti-ischemic effects in an exvivo model of an ischemia-reperfusion-induced rat heart.

• Journal of Chest Surgery
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• 제23권6호
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• pp.1090-1106
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• 1990

This study was undertaken to investigate whether adenosine administered during cardioplegic arrest could enhance myocardial protection and improve recovery of function after ischemia. Isolated Langendorff-perfused rat hearts were subjected to 40 minutes of normothermic [37oC] ischemia. Control hearts [n=10] received modified St. Thomas’ cardioplegic solution, and the remaining hearts received modified St. Thomas’ cardioplegic solution with either 20 \ulcornerM [n=10], 200 \ulcornerM [n=10] adenosine. After ischemia of 40 minutes and 30 minutes of reperfusion, left ventricular contractility was superior in all groups of adenosine-treated hearts compared with control hearts. Furthermore, there was a significant incremental increase in functional recovery with increasing dose of adenosine. Post-ischemic diastolic stiffness was significantly better in all adenosine groups compared with controls. No differences were noted in coronary flow or myocardial water content between adenosine-treated and control hearts. These data demonstrate that adenosine administered in these concentrations provides myocardial protection, preservation of myocardial ATP and creatine phosphokinase and improved post-ischemic functional hemodynamic recovery after normothermic ischemia, presumably metabolically by reducing depletion of adenosine triphosphate, inducing rapid cardiac arrest and enabling improved post-ischemic recovery.

• Journal of Chest Surgery
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• 제33권8호
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• pp.605-612
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• 2000

Background: Ischemic preconditioning enhances the tolerance of myocardium against ischemia/reperfusion injury, with the enhancement of the recovery of post-ischemic myocardial function. This study was disigned to assess whether the protective effect of ischemic preconditioning could provide one additional hour of myocardial preservation in four hour myocardial ischemia in a rate heart. Material and method: Fourty four Spargue-Dawley rats, weighing 300~450gm, were divided into four groups. Group 1(n=7) and group 3(n=12) were subjected to 30 minutes of aerobic Langendorff perfusion without ischemic preconditioning and then preserved in saline solution at 2~4$^{\circ}C$ for 4 hours and 5 respectively. Group 2(n=7) and group 4(n=18) were perfused in the same way for 20 minutes, followed by 3 minutes of global mormothermic ischemia and 10 minutes of perfusion and then preserved in the same cold saline solution for 4 hours and 5 hours respectively. Heart rate, left ventricular developed pressure(LVDP), and coronary flow were measured at 15 minutes during perfusion as baseline. Spontaneous defibrillation time was measured after reperfusion. Heart rate, LVDP, and coronary flow were also recorded at 15 minutes, 30 minutes, and 45 minutes during reperfusion. Samples of the apical left ventricular wall were studied using a transmission electron microscope. Result: Time of spontaneous defibrillation(TSD) was significantly longer in group 4 than in group 1(p<0.001), and TSD in group 1 was significantly longer in comparision to that of group 2(p<0.05). Heart rate at 45 minutes was significantly higher in group 1 than in group 4(p<0.05). Heart rate at 15 min was significantly higher in group 2 than in group 1(p<0.001) and in group 4 than in group 3(p<0.05). Left ventricular developed pressure(LVDP) at 30 minutes and 45 minutes was higher in group 1 than in group 4(p<0.01), LVDP at 45 minutes was higher in group 4 than in group 3(p<0.05). Rate-pressure product(RPP) at 30 minutes and 45 minutes was higher in group 1 than in group 4(p<0.05). RPP at 15 minutes was higher in group 2 than in group 1(p<0.01). RPP at 30 minutes and 45 minutes was higher in group 4 than in group 3(p<0.05). Group 2 showed relatively less sarcoplasmic edema and less nuclear chromatin clearance than group 1. Group 4 showed less myocardial cell damage than group 3, group 4 showed less myocardial cell damage than group 3, group 4 showed more myocardial cell edema than group 1. Conclusion: Ischemic preconditioning enhanced the recovery of postischemic myocardial function after 4 hours and 5 hours preservation. However, it was not demonstrated that ischemic preconditioning could definitely provide one additional hour of myocardial preservation in four hour myocardial ischemia in a rat heart.

• Preventive Nutrition and Food Science
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• 제6권1호
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• pp.43-50
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• 2001

The effects of cardiac ischemia-reperfusion and $\beta$-adrenergic stimulation on metabolic function and energetics were investigated in Lan gendorff-perfused spontaneously hypertensive rat (SHR) hearts. Sarcoplasmic reticulum {TEX}$Ca^{2+}${/TEX}-dependent ATPase and cardiac lactate dehydrogenase (LDH) are additionally studied. The perfusion medium (1.0 mM {TEX}$Ca^{2+}${/TEX}) contained 5 mM glucose(+5 U/L insulin) and 2 mM pyruvate as substrates. Global ischemia was induced by reducing perfusion pressure of 100 to 40 cm {TEX}$H_{2}${/TEX}O, followed by 20 min reperfusin. Isoproterenol (ISO, 1$\mu$M) was infused for 10 min. Coronary vascular resistance and myocardial oxygen consumption ({TEX}$MVO_{2}${/TEX}) of SHR were increased in parallel with enhanced venous lactate during ischemia and reperfusion compared to those of Sprague Dawley (SD) hearts. Although ischemia-induced increase in venous lactate and combined adenosine plus inosine was abolished, coronary vasodilation produced in SD during reperfusion. In SHR, depressed reactive hyperemia was associated with a fall in cardiac ATP and CrP/Pi ratio and a rise in intracellular lactate/Pyruvate ratio. On the other hand, ISO produced coronary functional hyperemia and an increase in {TEX}$MVO_{2}${/TEX}. However, these responses were less than those in SHR hearts. The ATPase activity of SHR was attenuated in free {TEX}$Ca^{2+}${/TEX} concentrations used under basal condition and with ISO compared to that of SD. Venous lactate output and cardiac LDH activity were augmented in SHR as influenced by ISO. These results demonstrate that coronary reactive and functional hyperemia was dpressed in SHR, which cold be explained by alterations in the cytosolic phosphorylation potential and the cytosolic redox state manipulated by LDH, and by abnormal free calcium handling.

• Nutrition Research and Practice
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• 제13권3호
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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.

• Journal of Chest Surgery
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• 제31권9호
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• pp.845-854
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• 1998

Background: S-2-(3 aminoprophlamino) ethylphosphorothioic acid(WR-2721) is one of the radical scavenging thiols. We tested its protective effects in the reperfused heart. Material and Method: The experimental setup was the constant pressure Langendorffs perfusion system. We investigated the radical scavenging properties of this compound in isolated rat hearts which were exposed to 20 minutes ischemia and 20 minutes reperfusion. Four experimental groups were used:group I, control, Amifostine 50 mg(1 mL) peritoneal injection 30 minutes before ischemia(group II), Amifostine 10 mg(0.2 mL) injection during ischemia through coronary artery(group III),and Amifostine 50 mg(1 mL) peritoneal injection 2 hrs before ischemia(group IV). The experimental parameters were the levels of latate, CK-MB, and adenosine deaminase(ADA) in frozen myocardium, the quantity of coronary flow,and left ventricular developed pressure, and it's dp/dt. Statistical analysis was performed using repeated measured analysis of variance and student t-test. Result: The coronary flow of group II and IV were less than group I and III at equilibrium state but recovery of coronary flow at reperfusion state of group II, III, and IV were more increased compared with group I. The change of systolic left ventricular devoloping pressure of group II and IV were less than control group at equilibrium state, which seemed to be the influence of the pharmacological hypotensive effect of amifostine. But it was higher compared with group I at reperfusion state. The lactic acid contents of group II were less than control group in frozen myocardium.(Group I was 0.20 0.29 mM/g vs Group II, which was 0.10 0.11 mM/g). The quantity of CK-MB in myocardial tissue was highest in group IV (P=0.026 I: 120.0 97.8 U/L vs IV: 242.2 79.15 U/L). The adenosine deaminase contents in the coronary flow and frozen myocardium were not significantly different among each group. Conclusion: Amifostine seemed to have significant cardioprotective effect during ischemia and reperfusion injuries of myocardium.

• Journal of Ginseng Research
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• 제33권4호
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• pp.283-293
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• 2009

Ginsenosides, one of the most well-known traditional herbal medicines, are used frequently in Korea for the treatment of cardiovascular symptoms. The effects of ginseng saponin on ischemia-induced isolated rat heart were investigated through analyses of hemodynamic changes including perfusion pressure, aortic flow, coronary flow, and cardiac output. Isolated rat hearts were perfused and then subjected to 30 min of global ischemia followed by 60 min of reperfusion with modified Kreb's Henseleit solution. Myocardial contractile function was continuously recorded. Ginseng saponin administered before inducing ischemia significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output. The ginseng saponin administered group significantly recovered all of the hemodynamic parameters, except heart rate, after ischemia-reperfusion (I/R) compared with ischemia control. The intracellular calcium ($[Ca^{2+}]_i$) content in rat neonatal cardiomyocytes was quantitatively determined. Administration of ginseng saponin significantly prevented $[Ca^{2+}]_i$ increase that had been induced by simulated I/R in vitro (p<0.01) in a dose-dependent manner, suggesting that the cardioprotection of ginseng saponin is mediated by the inhibition of $[Ca^{2+}]_i$ increase. Overall, we found that the administration of ginseng saponin has cardioprotective effects on the isolated rat heart after I/R injury. These results indicate that ginseng saponin has distinct cardioprotective effects in an I/R-induced rat heart.

• The Korean Journal of Physiology and Pharmacology
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• 제24권2호
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• pp.173-183
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• 2020

An in vitro model for ischemia/reperfusion injury has not been well-established. We hypothesized that this failure may be caused by serum deprivation, the use of glutamine-containing media, and absence of acidosis. Cell viability of H9c2 cells was significantly decreased by serum deprivation. In this condition, reperfusion damage was not observed even after simulating severe ischemia. However, when cells were cultured under 10% dialyzed FBS, cell viability was less affected compared to cells cultured under serum deprivation and reperfusion damage was observed after hypoxia for 24 h. Reperfusion damage after glucose or glutamine deprivation under hypoxia was not significantly different from that after hypoxia only. However, with both glucose and glutamine deprivation, reperfusion damage was significantly increased. After hypoxia with lactic acidosis, reperfusion damage was comparable with that after hypoxia with glucose and glutamine deprivation. Although high-passage H9c2 cells were more resistant to reperfusion damage than low-passage cells, reperfusion damage was observed especially after hypoxia and acidosis with glucose and glutamine deprivation. Cell death induced by reperfusion after hypoxia with acidosis was not prevented by apoptosis, autophagy, or necroptosis inhibitors, but significantly decreased by ferrostatin-1, a ferroptosis inhibitor, and deferoxamine, an iron chelator. These data suggested that in our SIR model, cell death due to reperfusion injury is likely to occur via ferroptosis, which is related with ischemia/reperfusion-induced cell death in vivo. In conclusion, we established an optimal reperfusion injury model, in which ferroptotic cell death occurred by hypoxia and acidosis with or without glucose/glutamine deprivation under 10% dialyzed FBS.

• The Korean Journal of Physiology and Pharmacology
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• 제3권6호
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• pp.579-586
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• 1999

Complement-mediated neutrophil activation has been hypothesized to be an important mechanism of reperfusion injury. It has been proposed that C1 esterase inhibitor (C1 INH) may prevent the complement- dependent activation of polymorphonuclear leukocytes (PMNs) that occurs within postischemic myocardium. Therefore, The effect of C1 INH was examined in neutrophil dependent isolated perfused rat heart model of ischemia (I) (20 min) and reperfusion (R) (45 min). Administration of C1 INH (5 mg/Kg) to I/R hearts in the presence of PMNs $(100{\times}10^6)$ and homologous plasma improved coronary flow and preserved cardiac contractile function (p＜0.001) in comparison to those I/R hearts receiving only vehicle. In addition, C1 INH significantly (p＜0.001) reduced PMN accumulation in the ischemic myocardium as evidenced by an attenuation in myeloperoxidase activity. These findings demonstrate the C1 INH is a potent and effective cardioprotective agent inhibits leukocyte-endothelial interaction and preserves cardiac contractile function and coronary perfusion following myocardial ischemia and reperfusion.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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• pp.53-57
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• 1999

The activities of myocardial antioxidant enzymes are known to increase in the hearts preconditioned with the brief episodes of ischemia. This study was undertaken to elucidate the possible involvement of adenosine in the stimulation of myocardial catalase induced by the brief regional ischemia in rabbit hearts. Coronary artery descending the middle anterior wall of left ventricle was occluded for 15 min, followed by 1 hr of reperfusion. Upon reperfusion after the brief ischemia, the activity of catalase increased significantly in both ischemic and non-ischemic parts of myocardium. Pretreatment of the heart with theophylline, a non-specific adenosine receptor blocker, completely abolished the increase of catalase activity in both the ischemic and non-ischemic regions of myocardium. On the other hand, the administration of exogenous adenosine instead of the ischemia failed to increase the catalase activity in in vivo hearts. Moreover, adenosine infusion did not affect the catalase activity in the isolated, perfused hearts either. These results suggest that the endogenous adenosine released from the ischemic myocardium is involved in the activation of catalase induced by brief ischemia, but that adenosine may not be a final direct activator of cellular catalase in the myocardium.