• 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.

• Journal of Chest Surgery
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• v.18 no.4
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• pp.732-739
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• 1985

This study was experimentally undertaken to evaluate the effect of the coronary vasodilator-mixed cardioplegic solution on myocardial protection during prolonged aortic cross-clamping. The dogs were divided into two groups: control group A[received hypothermic cardioplegic solution without any additive coronary vasodilator], and comparing group 8[received hypothermic cardioplegic solution, mixed with various coronary vasodilators and Inderal]. Group A further was divided into two subgroups: subgroup A-1[ischemic time, 90 minutes], and subgroup A-2 [ischemic time, 240 minutes]. Group B further was divided into five subgroups: subgroup B-1 [received papaverine mixed hypothermic cardioplegic solution], subgroup B-2[received nitroglycerin mixed hypothermic cardioplegic solution], subgroup B-3 [received nitroprusside mixed hypothermic cardioplegic solution, subgroup B-4[received hydralazine mixed hypothermic cardioplegic solution], and subgroup B-5 [received inderal mixed hypothermic cardioplegic solution]. The specimens from all of the subgroups were studied by electron microscopic examination. The specimens of subgroups [B-l, B-2 8-3, and B-4], received coronary vasodilators mixed hypothermic cardioplegic solutions, were also compared by methylene blue induced staining of the myocardium and coronary vessels. The results obtained were as followings: l. On electron microscopic examination, all of the specimens, including subgroup A-2, showed no irreversible change of the myocardium. But the best result was obtained from the subgroup B-l, treated by papaverine mixed hypothermic cardioplegic solution. The subgroup B-2, treated by nitroglycerin, was next. And the subgroup B-5, treated by Inderal, was agreeable, comparing the electron microscopic finding with control group in the effect of myocardial protection. 2. The distribution in the myocardium of cardioplegic solution was demonstrated with the aid of methylene blue staining in the subgroups of B-l, B-2, B-3, and B-4, and they were the groups treated by papaverine, nitroglycerin, nitroprusside, and hydralazine in their grouping order. The best result was obtained from the subgroup B-1 [papaverine]. The subgroup B-2 [nitroglycerin] was next. The subgroup B-3 [nitroprusside] was moderate in finding of the colorization. The subgroup B-4 [hydralazine] was the poorest in the distribution of the cardioplegic solution in the myocardium. From these results, it appeared that myocardial protection during ischemic arrest for open heart surgery could be enhanced considerably when coronary dilatation was assured.

• Journal of Chest Surgery
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• v.21 no.6
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• pp.979-983
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• 1988

Calcium channel blockers may prevent myocardial injury during cardioplegia and reperfusion. This study was done to evaluate the effects of diltiazem cardioplegia on myocardial protection during ischemic arrest and recovery of myocardial function after reperfusion. Four formulations of crystalloid cardioplegic solutions, GIK solution[group I, n=12], diltiazem[lug/ml GIK] in GIK solution[group II, n=7], ],diltiazem[2ug/ml GIK] in GIK solution[group III, n=6] and diltiazem[4ug/ml GIK] in GIK solution[group IV, n=6] were compared in isolated working rat heart subjected to a long period [2 hours] of hypothermic arrest with multi-dose infusion. Diltiazem cardioplegia[group II, III and IV]was found to be superior in nearly all aspects. Diltiazem cardioplegia showed faster recovery of regular rhythm and lower incidence of ventricular fibrillation than group I did. In comparing mechanical function in all experimental hearts, the mean postischemic recoveries of aortic flow, cardiac output, peak aortic pressure, stroke volume and stroke work[expressed as a percentage of its preischemic control] were significantly greater in group II, III and IV[diltiazem cardioplegia] than in group I. The infused amount of cardioplegic solution was more increased by the addition of diltiazem to GI K solution. [p < 0.01] Creatine kinase leakage tended to be lower in hearts receiving diltiazem cardioplegia, especially in group III and IV[p<0.05] than in those receiving GIK solution only[group I]. Diltiazem cardioplegia results in the increased flow of cardioplegic solution and the decreased ischemic injury of myocardium during ischemic arrest and the improved recovery of myocardial function after reperfusion, and a dose-response relation must be established before clinical use.

• Journal of Chest Surgery
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• v.37 no.6
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• pp.543-545
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• 2004

Postinfarction ventricular septal defect often induces cardiogenic shock and requires operative treatment early after myocardial infarction. Although the operative mortality of this disease has decreased during the past 3 decades, it is still relatively high. In this case, to prevent global myocardial ischemia, we used the technique of repair of postinfarction ventricular septal defect on a beating heart. This approach does not requir aortic cross-clamping and provides superior myocardial protection.

• Journal of Chest Surgery
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• v.33 no.8
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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.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.743-754
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• 2023

Background: Myocardial fibrosis post-myocardial infarction (MI) can induce maladaptive cardiac remodeling as well as heart failure. Although 20(S)-ginsenoside Rg3 (Rg3) has been applied to cardiovascular diseases, its efficacy and specific molecular mechanism in myocardial fibrosis are largely unknown. Herein, we aimed to explore whether TGFBR1 signaling was involved in Rg3's anti-fibrotic effect post-MI. Methods: Left anterior descending (LAD) coronary artery ligation-induced MI mice and TGF-β1-stimulated primary cardiac fibroblasts (CFs) were adopted. Echocardiography, hematoxlin-eosin and Masson staining, Western-blot and immunohistochemistry, CCK8 and Edu were used to study the effects of Rg3 on myocardial fibrosis and TGFBR1 signaling. The combination mechanism of Rg3 and TGFBR1 was explored by surface plasmon resonance imaging (SPRi). Moreover, myocardial Tgfbr1-deficient mice and TGFBR1 adenovirus were adopted to confirm the pharmacological mechanism of Rg3. Results: In vivo experiments, Rg3 ameliorated myocardial fibrosis and hypertrophy and enhanced cardiac function. Rg3-TGFBR1 had the 1.78×10^-7 M equilibrium dissociation constant based on SPRi analysis, and Rg3 inhibited the activation of TGFBR1/Smads signaling dose-dependently. Cardiac-specific Tgfbr1 knockdown abolished Rg3's protection against myocardial fibrosis post-MI. In addition, Rg3 downregulated the TGF-β1-mediated CFs growth together with collagen production in vitro through TGFBR1 signaling. Moreover, TGFBR1 adenovirus partially blocked the inhibitory effect of Rg3. Conclusion: Rg3 improves myocardial fibrosis and cardiac function through suppressing CFs proliferation along with collagen deposition by inactivation of TGFBR1 pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.289-295
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• 2002

To certify the protective effect of herbal medicine against oxygen free radical-induced myocardiotoxicity, cytotoxicity was measured using MTT, LDH activity and Beating rate assay in the presence of Guaruhaebaekbanha-tang(GHBT) extracts or single constituents of this prescription. Myocardial toxicity was evaluated in neonatal rat myocardiocytes in cultures. In the present study, xanthine oxidase/hypoxanthine(XO/HX) resulted in a decrease in cell viability, increases in LDH activity in culture medium and decreases in beating rate in cultured myocardial cells. In the effect of GHBT extract, it showed the prevention from the XO/HX-induced cardiotoxicity by the increases of cell viability and beating rate as well as the decrease of LDH activity. In the protective effect of Fructus Trichosanthis(FT), Bulbus Allii Macrostemi(BAM) and Rhizoma Pinelliae(RP), all the extracts were significantly effective in the protection of XO/HX-induced cardiotoxocity in cultured myocardial cells by the increase of beating rate as well as th decrease of LDH activity. From these results, they show that XO/HX is cardiotoxic in cultured myocardial cells derived from neonatal rat, and it suggests that GHBT, FT, SAM, RP extracts are positively effective in the blocking in XO/HX-induced cardiotoxicity.

• Journal of Chest Surgery
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• v.24 no.4
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• pp.345-351
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• 1991

The myocardial temperature was monitored in 19 patients of open heart surgery using the Shiley myocardial temperature probe in Department of Thoracic and Cardiovascular Surgery, Yeungnam University Hospital. The myocardial temperature were measured time-wise: initial and 15 minutes following the infusion of the cardioplegic solution into the aortic root and upon reinfusion, which is 30 minutes apart from the initial. The measurements were made in the anterior wall of the right ventricle, the posterior wall of the left ventricle and the interventricular septum. Immediately after initial infusion, the temperature of the right ventricle[10.7 $\pm$4.3oC] was the lowest and that of the left ventricle[12.9$\pm$3.9 oC] the highest in the mean values among all 19 patients. However, no significant differences were noted among the different regions. At 15 minutes after infusion, the lowest temperature was in the right ventricle[17.5$\pm$5.1 oC], followed by interventricular septum[17.9$\pm$2.9 oC], and left ventricle[21.4$\pm$2.5 oC]. At 30 minutes after infusion, the lowest temperature was measured in the interventricular septum[13.6$\pm$2.7 oC ], followed by right ventricle[13.8$\pm$4.0 oC] and left ventricle[14.5$\pm$4.5 oC ]. Evaluating changes of myocardial temperature according to postinfusion time, the temperature at 15 minutes after infusion showed significant increase as compared with that immediately after the infusion in all three regions[p<0.05] and the temperature at 30 minutes after infusion showed significant decrease as compared with that at 15 minutes after the infusion in the left ventricle and the interventricular septum[p<0.05]. The left ventricle was rewarmed most rapidly and its temperature the highest in the mean values, Accordingly, the maintenance of optimal hypothermia of the left ventricle indicated a very careful factor in myocardial protection.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.1031-1036
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• 2003

To certify the protective effect of herbal medicine against oxygen free radical-induced myocardiotoxicity, cytotoxicity was measured using TBARS assay and Beating rate in the presence of Tongryeong-san(TRS) extracts or single constituents of this prescription. Myocardial toxicity was evaluated in neonatal rat myocardiocytes in cultures. In the present study, xanthine oxidase/hypoxanthine (XO/HX) resulted in a increase in lipid peroxidation and decreases in beating rate in cultured myocardial cells. In the effect of TRS extract, it showed the prevention from the XO/HX-induced cardiotoxicity by the increases of beating rate as well as the decrease of lipid peroxidation, In the protective effect of Faeces Trogopterori(FT), Pollen Typhae(PT), Caulis Akebiae(CA) and Radix Paeoniae Rubra(PRR), all the extracts were significantly effective in the protection of XO/HX-induced cardiotoxocity in cultured myocardial cells by the increase of beating rate as well as th decrease of lipid peroxidation. From these results, they show that XO/HX is cardiotoxic in cultured myocardial cells derived from neonatal rat, and it suggests that TRS, FT, PT, CA and PRR extracts are positively effective in the blocking in XO/HX-induced cardiotoxicity.

• 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.