• Archives of Pharmacal Research
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• v.29 no.3
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• pp.241-248
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• 2006

Angiotensin converting enzyme (ACE) inhibitors have cardioprotective effects in different species including human. This cardioprotective effect is mainly due to the inhibition of bradykinin (BK) degradation rather than inhibition of the conversion of angiotensin I to angiotensir. II. Bradykinin, a nonapeptide, has been considered to be the potential target for various enzymes including ACE, neutral endopeptidase 24.11, carboxypeptidase M, carboxypeptidase N, proline aminopeptidase, endopeptidase 24.15, and meprin. In the present study, the coronary vascular beds of Sprague Dawley rat isolated hearts were perfused (single passage) with Krebs solution alone or with different concentrations of BK i.e. $2.75{\times}10^{-10},\;10^{-7},\;10^{-6}\;and\;10^{-5}M$ solution. Percent degradation of BK was determined by radioimmunoassay. The degradation products of BK after passing through the isolated rat-hearts were determined using RP-HPLC and mass spectroscopy. All the four doses of BK significantly decreased the perfusion pressure during their passage through the hearts. The percentage degradation of all four doses was decreased as the concentration of drug was increased, implying saturation of a fixed number of active sites involved in BK degradation. Bradykinin during a single passage through the hearts degraded to give [1-7]-BK as the major metabolite, and [1-8]-BK as a minor metabolite, detected on HPLC. Mass spectroscopy not only confirmed the presence of these two metabolites but also detected traces of [1-5]-BK and arginine. These findings showed that primarily ACE is the major cardiac enzyme involved in the degradation of bradykinin during a single passage through the coronary vascular of bed the healthy rat heart, while carboxypeptidase M may have a minor role.

• Journal of Ginseng Research
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• v.31 no.1
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• pp.23-33
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• 2007

Ginsenosides are one of the most well-known traditional herbal medicines frequently used for the treatment of cardiovascular symptoms in korea. The anti-ischemic effects of the mixture of ginsenoside $Rg_3$, and CK on ischemia-induced isolated rat heart were investigated through analyses of changes in hemodynamics ; blood pressure, aortic flow, coronary flow, and cardiac output. The subjects in this study were divided into four groups: normal control, the mixture of ginsenoside $Rg_3$ and CK, an ischemia-induced group without any treatment, and an ischemia-induced group treated with the mixture of ginsenoside $Rg_3$ and CK. There were no significant differences in perfusion pressure, aortic flow, coronary flow and cardiac output between them before ischemia was induced. The supply of oxygen and buffer was stopped for five minutes to induce ischemia in isolated rat hearts, and the mixture of ginsenoside $Rg_3$ and CK was administered during ischemia induction. Treatments of the mixture of ginsenoside $Rg_3$ and CK significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions. In addition, hemodynamics (except heart rate) of the group treated with the mixture of ginsenoside $Rg_3$ and CK significantly recovered 60 minutes after reperfusion compared to the control group (mixture+ischemia vs ischemia - average perfusion pressure: 74.4${\pm}$2.97% vs. 85.1${\pm}$3.01%, average aortic flow volume: 49.11${\pm}$2.72% vs. 59.97${\pm}$2.93%, average coronary flow volume: 58.50${\pm}$2.81% vs. 72.72${\pm}$2.99%, and average cardiac output: 52.47${\pm}$2.78% vs. 63.11${\pm}$2.76%, p<0.01, respectively). These results suggest that treatment of the mixture of ginsenoside $Rg_3$ and CK has distinct anti-ischemic effects in ex vivo model of ischemia-induced rat heart.

• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.299-305
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• 1997

In order to investigate the pharmacological properties of ι-muscone, effects of ι-muscone and musk were studied on the cardiovascular system with various experimental models. In isolated rat aorta, ι-muscone and musk made the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) in endothelium-containing rings of the rat aorta, but not in endothelium-denuded rings. However, ι-muscone and musk in the presence of the inhibitor of NO synthase and guanylate cyclase did not make the relaxation of blood vessels. In spontaneously hypertensive rats (SHRs), ι-muscone and musk slightly reduced blood pressure but significantly decreased heart rate. In the isolated perfused rat hearts, ι-muscone and musk did not affect significantly on LVDP, contractile force, coronary flow and (-dp/dt)/(+dp/dt). These results suggest that ι-muscone and musk have weak cardiovascular effects with relaxation of blood vessel and decrease of heart rate, but without significant cardiac functions.

• Journal of Chest Surgery
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• v.28 no.5
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• pp.443-446
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• 1995

The present study was designed to determine whether cyclosporine A inhibits Major Histocompatibility Complex Class II antigen[MHC II expression in the allograft rat heart myocardium. In this rat allograft study we also tried to elucidate whether CSA inhibits MHC II in a dose dependent way. Hearts were isolated from LBN rats weighing 200-250 grams and heterotopically transplantated into the abdomen of weight-matched ACI rats. The ACI rats were randomly assigned to one of the three experimental groups according to cyclosporine dosage: {1}control [no CSA , n=6 {2}CSA 5 mg/day , n=5 {3}CSA 10 mg/day, n=5. The transplanted hearts were harvested 5 days postoperatively and analyzed. MHC II expression was detected by indirect immunoperoxidase staining and quantified via computer image analysis system. The % positive area reading was obtained in each slide [50 areas per group and compared to other groups. Significant differences were noted between three groups [p<0.05 . We conclude that CSA inhibits MHC II in heterotopically transplanted allograft rat heart in a dose dependent way.

• Journal of Chest Surgery
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• v.23 no.1
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• pp.9-15
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• 1990

This study was designed to investigate the protective effect of chlorpromazine against the reperfusion injury of myocardium after high potassium cardioplegic arrest. Langendorff`s preparations of rat heart were infused with high potassium cardioplegic solution[St. Thomas Hospital Solution] at 25oC. Chlorpromazine [10-7Ｍ] increased the recovery of myocardial contractility[dp/dt], left ventricular pressure[LVP], and coronary flow rate of the reperfused heart. Both in control and experimental groups, the restoration of myocardial activity could not reach to the level of preplegic control. These results suggest that the etiologic factors of the reperfusion injury include the influence of high potassium cardioplegic solution and/or reperfusion itself, and that chlorpromazine protects myocardium from the reperfusion injury.

• YAKHAK HOEJI
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• v.45 no.3
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• pp.276-281
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• 2001

The present study was conducted to evaluate the effect of KST221085, a newly synthesized antidiabetic agent, on the hearts from streptozotocin (STZ)-induced diabetic rats. In isolated diabetic hearts, left ventricular developed pressure (LVDP), heart rate (HR) and coronary flow rate (CFR) were decreased compared to normal control, indicating cardiovascular dysfunction in diabetic heart. The treatment with 10 $\mu$M KST221085 remarkably improved the diabetes-induced contractile impairment, without any influence on HR. Reduced coronary flow in diabetic heart was also significantly increased by treatment with 10 $\mu$M KST221085. In isolated aorta from diabetic rat, treatment with 10 $\mu$M KST221085 increased endothelium-dependent relaxation, suggesting that KST221085 can improve the impaired endothelial function in diabetic aorta. Our results suggest that KST221085 treatment can improve the cardiovascular dysfunction in STZ-induced diabetic rats.

• The Journal of Internal Korean Medicine
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• v.18 no.2
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• pp.160-166
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• 1997

To evaluate the effect of acupuncture on the hypertension, the study was done by acupuncture on bilateral Inyong(ST9) with rats which are normal and acutely increased hypertensive. The results are as follows: 1. Under the normal condition, the acupuncture on bilateral Inyong caused a quick drop of mean arterial pressure(MAP), but heart rate(HR) was not changed significantly. 2. To increase the blood pressure, acutely epinephrine was administered and it caused a increase in both MAP and HR. With acupuncture, the MAP was decreased while HR did not show a significant change. In conclusion, the acupuncture was somewhat effective in lowering the mean arterial pressure in the rat.

• Journal of Korean Neurosurgical Society
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• v.47 no.4
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• pp.287-290
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• 2010

Objective : The authors evaluated the accuracies and ease of use of several commonly used microanastomosis training models (synthetic tube, chicken wing, and living rat model). Methods : A survey was conducted among neurosurgeons and neurosurgery residents at a workshop held in 2009 at the authors' institute. Questions addressed model accuracy (similarity to real vessels and actual procedures) and practicality (availability of materials and ease of application in daily practice). Answers to each question were rated using a 5-point scale. Participants were also asked what types of training methods they would chose to improve their skills and to introduce the topic to other neurosurgeons or neurosurgery residents. Results : Of the 24 participants, 20 (83.3%) responded to the survey. The living rat model was favored for model accuracy (p<0.001; synthetic tube $-0.95{\pm}0.686$, chicken wing, $0.15{\pm}0.587$, and rat, $1.75{\pm}0.444$) and the chicken wing model for practicality (p<0.001; synthetic tube $-1.55{\pm}0.605$, chicken wing, $1.80{\pm}0.523$, and rat,$1.30{\pm}0.923$). All (100%) chose the living rat model for improving their skills, and for introducing the subject to other neurosurgeons or neurosurgery residents, the chicken wing and living rat models were selected by 18 (90%) and 20 (100%), respectively. Conclusion : Of 3 methods examined, the chicken wing model was found to be the most practical, but the living rat model was found to represent reality the best. We recommend the chicken wing model to train surgeons who have mastered basic techniques, and the living rat model for experienced surgeons to maintain skill levels.

• Korean Journal of Clinical Pharmacy
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• v.7 no.1
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• pp.33-39
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• 1997

Cardiac and antihypertensive effects of BMS-180448, a cardiac-selective ATP-sensitive potassium channel opener, and its newly synthesized derivatives KR-31281, KR-31282 and KR-31299 were evaluated in isolated perfused rat hearts (25 min global ischemia/30 min reperfusion) and conscious rats. Three new compounds $(10\;{\mu}M)$ induced positive inotropism as evidenced by increased LVDP (left ventricular developed pressure) and RPP (Rate-Pressure Product) in nonischemic rat heart. HR-31299 increased CF (coronary flow) and HR (heart rate) but the other two had no effects. KR-31282, KR-31281 and HR-31299 had a tendency to increase reperfusion LVDP and RPP compared with vehicle, while the latter two significantly reduced reperfusion EDP with a tendency to inclose TTC (time to contracture). All three KR-compounds had very weak effects on MBP and HR in conscious rats. These results indicate that KR-31281 and HR-31299 may have some cardioprotective effects, although weaker than BMS-180448, and their mode of action different from that of BMS-180448, despite the similarity in major structural moeity.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.4
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• pp.385-392
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• 1997

The phospholipase C (PLC)-mediated intracellular signal transduction pathway is considered to be involved in the regulation of blood pressure. However, little information is available concerning the distributional and functional significance of PLC in the genetic hypertensive rats. As the first step of knowing the role of PLC on hypertension, we investigated the distribution of 6 PLC isozymes $(PLC-{\beta}1,\;-{\beta}3,\;-{\beta}4,\;-{\gamma}1,\;-{\gamma}2\;and\;-{\delta}1)$ in the heart and brain, which are concerned with hypertension, in the normotensive Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR) using the western blotting and immunocytochemistry. The immunoreactivities of PLC isozymes in brain were detected, but there were no distributional and quantitative differences between the WKY and SHR. In the heart, but the immunoreactivities to $PLC-{\beta}1$ and $-{\gamma}2$ in the SHR were higher than those in WKY. In immunocytochemistry to confirm these western blotting data, $PLC-{\beta}1$ and $-{\gamma}2$ were localized in cardiac myocytes and the intensities of immunoreactivity in SHR were stronger than that in WKY. These results suggest that $PLC-{\beta}1$ and $-{\gamma}2$ would have possibility to concern with the establishment of spontaneous hypertension.