• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.21-29
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• 2004

Purpose: Much evidence suggests long-term cigarette smoking alters coronary vascular endothelial response. On this study, we applied nonnegative matrix factorization (NMF), an unsupervised learning algorithm, to CO-less $H_2^{15}O-PET$ to investigate coronary endothelial dysfunction caused by smoking noninvasively. Materials and methods: This study enrolled eighteen young male volunteers consisting of 9 smokers $(23.8{\pm}1.1\;yr;\;6.5{\pm}2.5$ pack-years) and 9 nonsmokers $(23.8{\pm}2.9 yr)$. They do not have any cardiovascular risk factor or disease history. Myocardial $H_2^{15}O-PET$ was performed at rest, during cold ($5^{\circ}C$) pressor stimulation and during adenosine infusion. Left ventricular blood pool and myocardium were segmented on dynamic PET data by NMF method. Myocardial blood flow (MBF) was calculated from input and tissue functions by a single compartmental model with correction of partial volume and spillover effects. Results: There were no significant difference in resting MBF between the two groups (Smokers: 1.43 0.41 ml/g/min and non-smokers: $1.37{\pm}0.41$ ml/g/min p=NS). during cold pressor stimulation, MBF in smokers was significantly lower than 4hat in non-smokers ($1.25{\pm}0.34$ ml/g/min vs $1.59{\pm}0.29$ ml/gmin; p=0.019). The difference in the ratio of cold pressor MBF to resting MBF between the two groups was also significant (p=0.024; $90{\pm}24%$ in smokers and $122{\pm}28%$ in non-smokers.). During adenosine infusion, however, hyperemic MBF did not differ significantly between smokers and non-smokers ($5.81{\pm}1.99$ ml/g/min vs $5.11{\pm}1.31$ ml/g/min ; p=NS). Conclusion: in smokers, MBF during cold pressor stimulation was significantly lower compared wi4h nonsmokers, reflecting smoking-Induced endothelial dysfunction. However, there was no significant difference in MBF during adenosine-induced hyperemia between the two groups.

• Korean Journal of Food Science and Technology
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• v.26 no.3
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• pp.213-220
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• 1994

Gastrodia (G) Rhizoma has been used clinically as an oriental herbal medicine with sedative, anticonvulsive, and depressor effects. The present study tested effects of G. Rhizoma extracts on the coronary circulation and myocardial oxygen consumption in perfused rat hearts. Sprague Dawley rats (SD) and spontaneously hypertensive rats (SHR) were employed as experimental animals and nonworking Langendorff heart perfusion technique introduced for heart experiments. G. Rhizoma extracts were prepared from grinding G. Rhizoma into powder, extracting in water and 50% ethanol for 4 or 16 hr and diluting with Krebs-Henseleit bicarbonate perfusion buffer to be 70%. Hearts were perfused with bicarbonate buffer oxygenated with 95% $O_{2}:$ 5% $CO_{2}$ at constant coronary perfusion pressure of $90cmH_{2}O$. The diluted extracts were infused into coronary arteries in a concentration of $1{\sim}5\;{\mu}M$ for $7{\sim}8 min. While in SD water- or ethanol-extracts of G. Rhizoma extracted for 16 hr increased coronary perfusate flow (CPF) and decreased coronary vascular resistance (CVR), ethanol-extracts in SHR produced coronary vasoconstriction associated with enhanced CVR. G. Rhizoma extracts-induced increase in CPF reduced myocardial oxygen extraction, and thus myocardial oxygen consumption ($MVO_{2}$) remained at that observed prior to infusion of extracts. In SD and SHR 16 hr-water-extracts markedly altered coronary venous effluent pH and $Pco_{2}$ and evoked metabolic acidosis, which could be a coronary vasodilator mechanism decreasing CVR. In this study, the extracts decreasing CVR in SD and SHR did not augment the lactate production. Therefore, although the effects of the extracts on cardiac function and coronary circulation depended on solvents and duration for extraction, the 16hr-water-extracts, at least, exhibited coronary vasodilation in SD and SHR. Conversely, ethanol-extracts constricted coronary arteries in SHR. G. Rhizoma extracts-induced vasodilation might be due to the metabolic acidosis rather than due to the increased lactate production. The results indicate that G. Rhizoma extracts obtained from proper extracting procedures can be used as a safe and clinically applicable herbal medicine in the cardiovascular diseases such as coronary artery disease and hypertension for vasodilatory and antihypertensive actions.

• Journal of Preventive Medicine and Public Health
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• v.27 no.2 s.46
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• pp.200-216
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• 1994

In present study, the authors investigated the possible effect of coffee consumption on serum cholesterol level in 1017 men between the ages of 40 and 59 years, who were randomly selected from the members of Seoul Cohort Study. Serum total cholesterol data was collected with other serologic indices (e.g. systolic blood pressure, diastolic blood pressure, hight, weight, etc.) through the program of biennial health check-up offered by Korean Medical Insurance Corporation (KMIC). The amount of coffee consumption was assessed by a self-administered questionnaire through mailing. Other confounding factors, such as age, body mass index, cigarette smoking, alcohol consumption, physical activity, and other dietary intake pattern were also determined by the questionnaire. The differences in means of serum total cholesterol in compared to non consumers were $-0.4{\pm}3.56mg/dl$ for those drinking less than 1 cup a day, $-0.6{\pm}3.60mg/dl$ for those drinking 1 cup a day, and $7.1{\pm}3.41mg/dl$ for those drinking more than 2 cups a day. Since smoking interacted the relationship between coffee consumption and serum total choleaterol, we re-analyzed those relationship in smokers and non-smokers separately Other atherogenic behaviors were well correlated with total cholesterol, so we adjusted the mean values of serum total cholesterol through multivariate model selection with age(r=0.12), total cigarette index (cigarette-years; r=0.10), Quetelet's index ($Kg/m^2$, r=0.16), daily calory expenditure (kcal/day, r=0.06), weekly meat and poultry consumption(g/week, r=0.05), weekly fish consumption (g/week, r=0.08), other caffeinated beverage intake (cups/week), and the amount of sugar and prim added to the coffee. Among those variables only age, Quetelet's index, fish consumption, and total cigarette index (in smokers) were remained in the models. After adjustment, the corresponing differences of total cholesterol in smokers were changed to $0.4{\pm}5.24mg/dl,\;-0.5{\pm}4.97mg/dl,\;and\;8.9{\pm}4.78mg/dl$, which were significantly different among themselves (P=0.011). In non-smokers, however, the differences were not statistically significant (P=0.76). Adjusted mean values of systolic blood pressure and diastolic blood pressure were also determined to evaluate the direct effect of coffee to cardiovascular system, but their means were not significantly different by coffee consumption(p=0.18 for SBP, p=0.48 for DBP). Asuming instant coffee in the most popular type of coffee in Korea, the association observed in our study between coffee and serum total cholesterol, especially in smokers, is very interesting finding for the connection between coffee and serum total cholesterol, because only 'boiled coffee' tend to show significant lipid raising effect rather than to other types of coffee, like filtered or espresso, in most of the western countries. We concluded that people who drink coffee more than 2 cups a day have significantly higher serum total cholesterol level than those who never drink coffee, especially in smokers.

• Journal of Chest Surgery
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• v.36 no.5
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• pp.242-254
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• 2003

Background: Most of the studies conducted have investigated the beneficial effects of ischemic preconditioning on normothermic myocardial ischemia. However, the effect of preconditioning could be attenuated through the use of multidose cold cardioplegia as practiced in contemporary clinical heart surgical procedures. The purpose of this study was to investigate whether preconditioning improves postischemic cardiac function in a model of $25^{\circ}C$ moderate hypothermic ischemic heart induced by cold cardioplegia in isolated rat hearts. Material and Method: The isolated Sprague-Dawley rat hearts were randomly assigned to four groups All hearts were perfused at 37$^{\circ}C$ for 20 minutes with Krebs-Henseleit solution before the baseline hemodynamic data were obtained, Group 1 consisted of preconditioned hearts that received 3 minutes of global ischemic preconditioning at 37$^{\circ}C$, followed by 5 minutes of reperfusion before 120 minutes of cardioplegic arrest (n=6). Cold (4$^{\circ}C$) St. Thomas Hospital cardioplegia solution was infused to induce cardioplegic arrest. Maintaining the heart at $25^{\circ}C$, infusion of the cardioplegia solution was repeated every 20 minutes throughout the 120 minutes of ischemic period. Group 2 consisted of control hearts that underwent no manipulations between the periods of equilibrium and 120 minutes of cardioplegic arrest (n=6). After 2 hours of cardioplegic arrest, Krebs solution was infused and hemodynamic data were obtained for 30 minuts (group 1, 2: cold cardioplegia group). Group 3 received two episodes of ischemic preconditioning before 30 min of 37$^{\circ}C$ normothermic ischemia and 30 minutes of reperfusion (n=6) Group 4 soloed as ischemic controls for group 3 (group 3, 4: warm ischemia group). Result: Preconditioning did not influence parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), rate-pressure product (RPP) and left ventricular dp/dt (LV dp/dt) in the cold cardioplegia group. (p=NS) However, preconditioning before warm ischemia attenuated the ischemia induced cardiac dysfunction, Improving the LVSP, LVEDP, RPP, and LV dp/dt. Less leakage of CPK and LDH were observed in the ischemic preconditioning group compared to the control group (p<0.05). Conclusion: Ischemic preconditioning improved postischemic cardiac function after warm ischemia, but did not protect cold cardioplegic hearts.

• Journal of Nutrition and Health
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• v.41 no.8
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• pp.733-741
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• 2008

In the present study, we comprehensively examined the associations of plasma levels of total adiponectin and high molecular weight (HMW) adiponectin with the features of cardiometabolic risks including body fat distribution, dyslipidemia, insulin resistance and inflammatory markers in a cross-sectional study of 110 treated hypertensive patients. Blood lipid profiles, high sensitivity C-reactive protein (hsCRP) and homeostasis model assessment of insulin resistance (HOMA- IR) derived from fasting glucose and insulin concentrations were determined. Plasma levels of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) were analyzed using ELISA. The results showed that plasma levels of HMW-adiponectin were negatively associated with body mass index (BMI, r = - 0.203, p < 0.05) and waist circumference (r = -0.307, p < 0.01), which was not shown in total adiponectin. Plasma levels of HMW-adiponectin were negatively associated with triglyceride (r = -0.223, p < 0.05) and positively associated with HDL-cholesterol (r = 0.228, p < 0.05). Plasma levels of adiponectin were positively associated with HDL-cholesterol (r = 0.224, p < 0.05). Plasma levels of HMW-adiponectin were negatively associated with hsCRP (r = -0.276, p < 0.01) and IL-6 (r = -0.272, p < 0.01). In addition, there were weak associations between plasma levels of HMWadiponectin and TNF-${\alpha}$ (r = -0.163, p = 0.07) and ICAM-1 (r = -0.158, p = 0.09). However, there were no significant associations of total adiponectin with inflammatory markers except hsCRP (r = -0.203, p < 0.05). Stepwise multiple linear regression analysis showed that only plasma levels of HMW-adiponectin was an independent factor influencing serum levels of hsCRP, a marker of systemic low grade inflammation, after adjusting for age, gender, BMI, waist circumference, alcohol intake, smoking status, blood lipids, total adiponectin and drug use (p < 0.01). These results suggest that HMW-adiponectin, rather than total adiponectin, is likely to be closely associated with the features of cardiometabolic risks in treated hypertensive patients and might be effective biomarker for the prediction of cardiovascular disease.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.4
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• pp.501-509
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• 2012

The dietary intake of whole grains is known to reduce the incidence of chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. In our previous study, hog millet (HM, $Panicum$ $miliaceum$ L.) water extract showed the highest anti-lipogenic activity among nine cereal types in 3T3-L1 cells. In this study, the effect of hog millet water extract on hepatic steatosis and lipid metabolism in mice fed a high fat diet was investigated. Mice were fed a normal-fat diet (ND), high-fat diet (HFD) or HFD containing 1% or 2% (w/w) HM for 7 weeks. Body weight and food intake were monitored during the study period. Insulin resistance by homeostasis model assessment (HOMA-IR), fasting lipid profile, hepatic fatty acid metabolism-related gene expression determined, and intraperitoneal glucose tolerance test (IGTT) were performed at the study's end. The results indicated that 1% and 2% HM diets effectively decreased liver weights, blood TG and T-cholesterol levels (p<0.05), while the HDL-cholesterol level was increased (p<0.05) compared to HFD-induced steatotsis mice. Hepatic lipogenic-related gene ($PPAR{\alpha}$, L-FABP, and SCD1) expressions decreased, whereas lipolysis- related gene (CPT1) expression increased in animals fed the 2% PME diet (p<0.05). In addition, mice fed 1% or 2% HM diet had markedly decreased IGTT and HOMA-IR, compared to the those of the HFD-induced hepatic steatosis control group (p<0.05). These results indicated that HM inhibited hepatic lipid accumulation by regulating fatty acid metabolism, and suggested that HM is useful in the chemoprevention or treatment of high fat-induced hepatic steatosis and hepatic steatosis-related disorders including hyperlipidemia, glucose sensitivity, and insulin resistance.

• 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.34 no.6
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• pp.447-453
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• 2001

Background: Although pulmonary resection is the standard approach for the management of pulmonary metastases from soft tissue sarcoma, most of them are unresectable and chemotherapy remains the only option. The effectiveness of the cytotoxic drugs may be limited by the toxicities that occur before the therapeutic dose is reached. The regional administration of doxorubicin using pulmonary arterial perfusion in a rodent model can produce 10 to 25 times higher concentrations in the lung than systemic administration with minimal systemic toxicities. However, it is unclear whether a high concentration of doxorubicin has beneficial effects for killing cancer cells. Material and Method: We studied this to evaluate the dose-dependent cytotoxic and apoptotic effects of doxorubicin on methylcholanthrene-induced rat fibrosarcoma(MCA) cells. This study examined the cytotoxicity and apoptosis-related gene expressions(Fas, FasL, Bax, caspase 1, caspase 2, caspase 8, Bcl-2, Bcl-xL, Bcl-xS) in MCA cells after 24 hours exposure to various concentrations of doxorubicin such as 1, 5, 10, 50, and 100 $\mu$M. Result: Dose-dependent cytotoxicity was observed after 24 hours exposure to doxorubicin. However, peak apoptosis after 24 hours exposure was observed at 5 $\mu$M of doxorubicin. Above 5 $\mu$M, apoptotic activity was decreased with dose-increment. All mRNA levels of apoptosis-related genes after 24 hours exposure were up-regulated above the control level at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment except caspase 8, which showed higher levels than the control level at 5 $\mu$M. Apoptosis-related protein levels were highest at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment. However, Bax and Bcl-xL proteins steadily showed higher levels than the control throughout the different concentrations of doxorubicin. Conclusion: These results suggest that apoptosis is the main cytotoxic mechanism in low concentrations of doxorubicin in MCA cells and apoptosis-related genes, such as Bax, caspase 8, and Bcl-xL, are involved. At high concentrations, doxorubicin still can kill MCA cells, even when apoptosis is inhibited, and have its propriety for achieving much cytotoxicity against MCA cells.

• Journal of Chest Surgery
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• v.32 no.9
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• pp.773-780
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• 1999

Background: It has been demonstrated that brief periods of calcium depletion and repletion (calcium-free preconditioning, CP) have cardioprotective effects as seen in ischemic preconditioning(IP) which enhances the recovery of post-ischemic contractile dysfunction and reduces the incidence of reperfusion-induced arrhythmia or infarct size after a prolonged ischemia. In the present study, we tested this paradoxical phenomenon in isolated rabbit hearts. Material and Method: Hearts isolated from New Zealand white rabbits(1.5∼2.0 Kg body weight) were perfused with Tyrode solution using the Langendorff technique. After stabilizing the baseline hemodynamics, the hearts were subjected to 45 minutes of global ischemia followed by 120 minutes of reperfusion with IP(IP group, n=7) or without IP (ischemic control group, n=7). IP was induced by a single episode of 5 minutes global ischemia and 10 minutes reperfusion. In the CP group(n=7), the hearts were subjected to perfusion with Tyrode solution with calcium depletion for 5 minutes and repletion for 10 minutes, and 45 minutes of ischemia and 120 minutes of reperfusion. Left ventricular function including developed pressure, dP/dt, heart rate, left ventricular end-diastolic pressure and coronary flow was measured. Infarct size was determined by staining with 1% triphenyltetrazolium chloride and planimetry. Data were analyzed by a one-way analysis of variance and Tukey's post-hoc test. Result: In comparison with the ischemic control group, IP significantly enhanced the recovery of the left ventricular function including the left ventricular developed pressure, contractility, and coronary flow; in contrast, these functional parameters of the CP group tended to be lower than those of the ischemic control group. However, the infarct size was significantly reduced by IP or CP(p<0.05). Conclusion: These results suggest that in isolated Langendorff-perfused rabbit heart model, CP(induced by single episode of 5 minutes calcium depletion and 10 minutes repletion) could not improve the post-ischemic contractile dysfunction(after a 45-minute global ischemia) but it has an infarct size-limiting effect.

• Journal of Preventive Medicine and Public Health
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• v.30 no.3 s.58
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• pp.585-598
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• 1997

Background : Although there are growing concerns about the adverse health effect of air pollution, not much evidence on health effect of current air pollution level had been accumulated yet in Korea. This study was designed to evaluate the chronic health effect of ai. pollution using Korean Medical Insurance Corporation (KMIC) data and air quality data. Medical insurance data in Korea have some drawback in accuracy, but they do have some strength especially in their national coverage, in having unified ID system and individual information which enables various data linkage and chronic health effect study. Method : This study utilized the data of Korean Environmental Surveillance System Study (Surveillance Study), which consist of asthma, acute bronchitis, chronic obstructive pulmonary diseases (COPD), cardiovascular diseases (congestive heart failure and ischemic heart disease), all cancers, accidents and congenital anomaly, i. e., mainly potential environmental diseases. We reconstructed a nested case-control study wit5h Surveillance Study data and air pollution data in Korea. Among 1,037,210 insured who completed? questionnaire and physical examination in 1992, disease free (for chronic respiratory disease and cancer) persons, between the age of 35-64 with smoking status information were selected to reconstruct cohort of 564,991 persons. The cohort was followed-up to 1995 (1992-5) and the subjects who had the diseases in Surveillance Study were selected. Finally, the patients, with address information and available air pollution data, left to be 'final subjects' Cases were defined to all lung cancer cases (424) and COPD admission cases (89), while control groups are determined to all other patients than two case groups among 'final subjects'. That is, cases are putative chronic environmental diseases, while controls are mainly acute environmental diseases. for exposure, Air quality data in 73 monitoring sites between 1991 - 1993 were analyzed to surrogate air pollution exposure level of located areas (58 areas). Five major air pollutants data, TSP, $O_3,\;SO_2$, CO, NOx was available and the area means were applied to the residents of the local area. 3-year arithmetic mean value, the counts of days violating both long-term and shot-term standards during the period were used as indices of exposure. Multiple logistic regression model was applied. All analyses were performed adjusting for current and past smoking history, age, gender. Results : Plain arithmetic means of pollutants level did not succeed in revealing any relation to the risk of lung cancer or COPD, while the cumulative counts of non-at-tainment days did. All pollutants indices failed to show significant positive findings with COPD excess. Lung cancer risks were significantly and consistently associated with the increase of $O_3$ and CO exceedance counts (to corrected error level -0.017) and less strongly and consistently with $SO_2$ and TSP. $SO_2$ and TSP showed weaker and less consistent relationship. $O_3$ and CO were estimated to increase the risks of lung cancer by 2.04 and 1.46 respectively, the maximal probable risks, derived from comparing more polluted area (95%) with cleaner area (5%). Conclusions : Although not decisive due to potential misclassication of exposure, these results wert drawn by relatively conservative interpretation, and could be used as an evidence of chronic health effect especially for lung cancer. $O_3$ might be a candidate for promoter of lung cancer, while CO should be considered as surrogated measure of motor vehicle emissions. The control selection in this study could have been less appropriate for COPD, and further evaluation with another setting might be necessary.