• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.393-402
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• 2019

Aurora kinases inhibitors, including ZM447439 (ZM), which suppress cell division, have attracted a great deal of attention as potential novel anti-cancer drugs. Several recent studies have confirmed the anti-cancer effects of ZM in various cancer cell lines. However, there have been no studies regarding the cardiac safety of this agent. We performed several cytotoxicity, invasion and migration assays to examine the anti-cancer effects of ZM. To evaluate the potential effects of ZM on cardiac repolarisation, whole-cell patch-clamp experiments were performed with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cells with heterogeneous cardiac ion channel expression. We also conducted a contractility assay with rat ventricular myocytes to determine the effects of ZM on myocardial contraction and/or relaxation. In tests to determine in vitro efficacy, ZM inhibited the proliferation of A549, H1299 (lung cancer), MCF-7 (breast cancer) and HepG2 (hepatoma) cell lines with $IC_{50}$ in the submicromolar range, and attenuated the invasive and metastatic capacity of A549 cells. In cardiac toxicity testing, ZM did not significantly affect $I_{Na}$, $I_{Ks}$ or $I_{K1}$, but decreased $I_{hERG}$ in a dose-dependent manner ($IC_{50}$: $6.53{\mu}M$). In action potential (AP) assay using hiPSC-CMs, ZM did not induce any changes in AP parameters up to $3{\mu}M$, but it at $10{\mu}M$ induced prolongation of AP duration. In summary, ZM showed potent broad-spectrum anti-tumor activity, but relatively low levels of cardiac side effects compared to the effective doses to tumor. Therefore, ZM has a potential to be a candidate as an anti-cancer with low cardiac toxicity.

• PNF and Movement
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• 제16권2호
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• pp.187-194
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• 2018

Purpose: This study aimed to assess the effect of rowing ergometer training on the aerobic capacity and strength of male high school students over a 12-week period. Methods: Fourteen high school students volunteered to participate in the study. The subjects were divided into two groups: seven subjects in the experimental group and seven in the control group. The subjects in the experimental group performed rowing ergometer training for 75 min per session at three days a week for 12 weeks. The exercise intensity set the maximum heart rate (HRmax) from 40% to 80%. Aerobic capacity was measured by ventilation, cardiac output, and oxygen intake per body weight. Strength was measured by grip strength and back strength before and after training. Results: A significantly increased ventilation (p=0.01), cardiac output (p=0.01), and oxygen intake per body weight (p=0.00) were found in the experimental group. A significantly increased grip strength in the right and left hands (p=0.00, 0.00) and back strength (p=0.04) were observed in the experimental group. Conclusion: Rowing ergometer training can be an effective combined exercise for aerobic capacity and strength of high school students.

• Clinical and Experimental Pediatrics
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• 제61권2호
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• pp.59-63
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• 2018

Purpose: Cardiomyopathy is becoming the leading cause of death in patients with Duchenne muscular dystrophy because mechanically assisted lung ventilation and assisted coughing have helped resolve respiratory complications. To clarify cardiopulmonary function, we compared cardiac function between the home ventilator-assisted and non-ventilator-assisted groups. Methods: We retrospectively reviewed patients with Duchenne muscular dystrophy from January 2010 to March 2016 at Gangnam Severance Hospital. Demographic characteristics, pulmonary function, and echocardiography data were investigated. Results: Fifty-four patients with Duchenne muscular dystrophy were divided into 2 groups: home ventilator-assisted and non-ventilator-assisted. The patients in the home ventilator group were older ($16.25{\pm}1.85years$) than those in the nonventilator group ($14.73{\pm}1.36years$) (P=0.001). Height, weight, and body surface area did not differ significantly between groups. The home ventilator group had a lower seated functional vital capacity ($1,038{\pm}620.41mL$) than the nonventilator group ($1,455{\pm}603.2mL$). Mean left ventricular ejection fraction and fractional shortening were greater in the home ventilator group, but the data did not show any statistical difference. The early ventricular filling velocity/late ventricular filling velocity ratio ($1.7{\pm}0.44$) was lower in the home ventilator group than in the nonventilator group ($2.02{\pm}0.62$. The mitral valve annular systolic velocity was higher in the home ventilator group (estimated ${\beta}$, 1.06; standard error, 0.48). Patients with Duchenne muscular dystrophy on a ventilator may have better systolic and diastolic cardiac functions. Conclusion: Noninvasive ventilator assistance can help preserve cardiac function. Therefore, early utilization of noninvasive ventilation or oxygen may positively influence cardiac function in patients with Duchenne muscular dystrophy.

• The Journal of Korean Physical Therapy
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• 제30권5호
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• pp.181-186
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• 2018

Purpose: This study investigated the effects of home-based exercise intensity on the aerobic capacity and 1 year re-hospitalization rate in patients with chronic heart failure (CHF). Methods: Forty seven patients with CHF (males 33, females 14, age $61.3{\pm}9.8years$) participated in this study. The patients were allocated randomly to 3 groups in accordance with home-based exercise intensity: no home based exercise (NHE, 40%, n=19), moderate intensity home-based exercise (MIHE, 43%, n=20), and high intensity home based exercise (HIHE, 17%, n=8). All patients completed the symptom-limited cardiopulmonary exercise (CPX) test safely at the cardiac rehabilitation hospital. Results: The NHE group significantly showed lower peak $VO_2$ and a higher $VE/VCO_2$ slope than the MIHE (p<0.05) and HIHE (p<0.01) groups. On the other hand, the NHE group did not show significant differences in the other hemodynamic responses, such as heart rate (HR) max, HR reserve, maximal systolic blood pressure (SBP), and SBP reserve. Nine out of 19 NHE patients (47%) were re-hospitalized related to heart disease and two out of 20 MIHE (10%) patients were re-hospitalized, but nobody in the HIHE group were re-hospitalized within 1 year from the CPX test. Conclusion: In patients with CHF, home-based self-exercise is one of the important factors for reducing the re-hospitalization rate. In addition, improved aerobic capacity is strongly associated with a lower re-hospitalization rate. In particular, re-hospitalized CHF patients showed significant differences in respiratory parameters and hemodynamic parameters compared to the non-re-hospitalized patients.

• Safety and Health at Work
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• 제4권3호
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• pp.156-159
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• 2013

Background: Cardiac pacemakers are known to be susceptible to strong electromagnetic fields (EMFs). This in vivo study investigated occurrence of electromagnetic interference with pacemakers caused by common environmental sources of EMFs. Methods: Eleven volunteers with a pacemaker were exposed to EMFs produced by two mobile phone base stations, an electrically powered commuter train, and an overhead high voltage transmission lines. All the pacemakers were programmed in normal clinically selected settings with bipolar sensing and pacing configurations. Results: None of the pacemakers experienced interference in any of these exposure situations. However, often it is not clear whether or not strong EMFs exist in various work environments, and hence an individual risk assessment is needed. Conclusions: Modern pacemakers are well shielded against external EMFs, and workers with a pacemaker can most often return to their previous work after having a pacemaker implanted. However, an appropriate risk assessment is still necessary after the implantation of a pacemaker, a change of its generator, or major modification of its programming settings.

• Journal of Chest Surgery
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• 제49권sup1호
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• pp.44-52
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• 2016

Background: This study investigates the perception of the general public regarding the concentration to metropolitan, hospitals of cardiac and cerebrovascular surgeries, and the perceived public need for government policies to resolve this issue. Methods: A total of 800 participants were recruited for our telephone interview survey. Quota sampling was performed, adjusting for age and sex, to select by various geographic regions. Sampling with random digit dialing was performed; we called the randomly generated telephone numbers and made three attempts for non-responders before moving on to a different telephone number. Results: Our sample population was 818 participants, 401 men (49.0%) and 417 women (51.0%). Our data showed that 85.5% of participants thought that cardiac surgery and neurosurgery patients are concentrated in large hospitals in Seoul. The principle reason for regional patients to want to receive surgery at major hospitals in Seoul was because of poor medical standards associated with regional hospitals (87.7%). We found that a vast majority of participants (97.5%) felt that government policies are needed to even out the clustering of cardiac surgery and neurosurgery patients, and that this clustering may be alleviated if policies that can specifically enhance the quality and the capacity of regional hospitals to carry out surgeries are adopted (98.3%). Conclusion: Government policy making must reflect public desiderata, and we suggest that these public health needs may be partially resolved through government-designated cardiac and neurosurgery specialist hospitals in regional areas.

• Reproductive and Developmental Biology
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• 제33권4호
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• pp.263-271
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• 2009

Cardiovascular diseases (CVDs) are one of the most cause of death around the world and fields of interest for cardiac stem cells. Also, current use of terminally differentiated adult cardiomyocytes for CVDs has limited regenerative capacity therefore any significant cell loss may result in the development of progressive heart failure. Human embryonic stem cells (hESCs) derived from blastocyst-stage embryos spontaneously have ability to differentiate via embryo-like aggregates (endoderm, ectoderm and mesoderm) in vitro into various cell types including cardiomyocyte. However, most effective molecule or optimized condition which can induce cardiac differentiation of hESCs is rarely studied. In this study, we developed both spontaneous and inductive cardiomyocyte-like cells differentiation from hESCs by treatment of induced-factors, 5-azacytidine, BMP-4 and cardiogenol C. On the one hand, spontaneous and inductive cardiomyocyte-like cells showed that cardiac markers are expressed for further analysis by RT-PCR and immunocytochemistry. Interestingly, BMP-4 greatly improved homogeneous population of the cardiomyocyte-like cells from hESCs CHA15 and H09. In conclusion, we verified that spontaneously differentiated cells showed cardiac specific markers which characterize cardiac cells, treated extrinsic factors can manage cellular signals and found that hESCs can undergo differentiation into cardiomyocytes better than spontaneous group. This finding offers an insight into the inductive factor of differentiated cardiomyocytes and provides some helpful information that may offer the potential of cardiomyocytes derived from hESCs using extrinsic factors.

• Journal of Chest Surgery
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• 제25권11호
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• pp.1185-1191
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• 1992

Cell mediated immunity is depressed following surgical procedure and the degree of immunosuppression is directly related to the magintude of the procedure, blood transfusion, and length of operation. So we would expect cardiac operations to be highly immunosuppressive, although little is konwn about their immunosuppressive effect. The nearly complete consumption of complement factors and decreased levels of IgM and IgG resulting in an impaired opsonizing capacity. Additionally, peripheral blood mononuclear cell counts including T-and B-lymphocytes and T-cell subsets are reduced. Depression of cell-mediated immunity following open-heart surgery is potentially detrimental because it could increase the susceptability of patients to viral and bacterial infection. We reviewed 20 patients after cardiac operation to search for changes in peripheral blood lymphocyte subsets. Lymphocyte subsets were measured by flow cytometer and the preoperative values of lymphocyte subsets were compared with those from the first, fourth, and seventh days after operation. After cardiac operation, total mumbers of T lymphocyte was severely depressed on the first postoperative day and returned to the preoperative level by the seventh day after operation. CD3, CD4, and CD8 lymphocytes were decreased on the first postoperative day and returned to the preoperative level by the seventh day also. There was four cases of wound infection and these patients had increased CD4 lympocyte and more decreased CD19 lymphocyte compared with the non-infected group. It is concluded from these data that cell-mediated immunity is significantly depressed for at least one week following open-heart surgery and this result was closely related to the postoperative infection.

• International Journal of Stem Cells
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• 제17권1호
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• pp.70-79
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• 2024

The efficacy of adipose-derived stem cells (ASCs) on myocardial infarction is limited due to poor survival and engraftment. Integrin-mediated cell adhesion is a prerequisite for its survival and homing. ASCs expressed insufficient integrin 𝛼₄, limiting their homing capacity. This study aims to characterize integrin 𝛼₄⁺ ASC subpopulation and investigate their therapeutic efficacy in myocardial infarction. We used fluorescence-activated cell sorting to harvest integrin 𝛼₄⁺ ASCs subpopulation, which were characterized in vitro and transplanted into myocardial infarction model. Positron emission tomography imaging were performed to measure infarction size. Cardiac cine magnetic resonance imaging was used to evaluate heart contractile function. Compared with the unfractionated ASCs, integrin 𝛼₄⁺ ASCs subpopulation secreted a higher level of angiogenic growth factors, migrated more rapidly, and exhibited a stronger anti-apoptotic capacity. Vascular cell adhesion molecule-1 was obviously up-regulated at 3 days after myocardial infarction, which interacted with integrin α₄ receptor on the surface of ASCs to enhance the survival and adhesion. Thus, we implanted unfractionated ASCs or integrin α₄⁺ ASCs subpopulation into the 3-day infarcted myocardium. Integrin α₄⁺ ASCs subpopulation exhibited more robust engraftment into the infarcted myocardium. Integrin α₄⁺ ASCs subpopulation more effectively decreased infarct size and strengthen cardiac function recovery than did the unfractionated ASCs. Integrin α₄⁺ ASCs subpopulation is superior to unfractionated ASCs in ameliorating ischemic myocardial damage in animal model. Mechanistically, their more robust engraftment into the infarct area, higher migratory capacity and their increased release of paracrine factors contribute to enhanced tissue repair.

• The Korean Journal of Physiology
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• 제24권2호
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• pp.249-260
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• 1990

Maximal cardiac output and oxygen uptake $(VO_{2max})$ were measured during treadmill exercise for seven top-class marathoners and nine non-athletes using impedance cardiograph developed by one of the authors (DW Kim). Results of this study are summarized as belows. 1) New shoes with sponge and silicon rubber attached to the soles were developed to reduce motion artifact during treadmill exercise. Ensemble everaging techneque with the developed shoes was also used to improve the measurement of stroke volume using impedance cardiography. 2) Maximal cardiac output of the athletes, 14.98 L/min, was significantly higher than that of the non-athletes, 13.46 L/min. As maximal heart rate of the marathoners is lower than that of non-athletes, stroke volume of the former is significantly larger than that of the latter. 3) $VO_{2max}$ of the marathoners, 59.38 ml/kg/min, was higher than that of the non-athletes, 40.22 ml/kg/min. At the anaerobic threshold. $VO_{2max}$ of the former was 62.3% of $VO_{2max}$ and this was significantly higher than that of the non-athletes, 57.2%, This results indicates that the marathoners have higher aerobic capacity than the non-athletes. 4) The marathoners showed larger $VO_2$ than the non-athletes at the same cardiac output, indicating that a-v $O_2$ of the former is higher than that of the latter. 5) Maximal systolic pressure of the marathoners was higher than that of the non-athletes, and so was maximal rate-pressure products. These results indicate that heart oxygen consumption rate $(hVO_2)$ of the marathoner is higher than that of the non-athletes is mainly due to higher stroke volume. And higher oxygen consumption of the marathoners is due to higher stroke volume. And higher oxygen consumption of the marathoners is due to their larger a-v $O_2$. The marathoners show both higher threshold and $VO_{2max}$. Especially, measurement of cardiac output during treadmill exercise by improved impedance cardiography is expected to contribute in study of cardiac function of athletes.