• Title/Summary/Keyword: Rabbit heart

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Pharmacokinetics of Anticancer Agent SB-31 in Rats & Rabbits and the Cardiovascular Effect on the Isolated Perfused Rat Heart & Blood Coagulation (SB-31의 Glycyrrhizin을 지표로 한 Rat과 Rabbit에서의 약물동태 및 심혈관계에 대한 효과 연구)

  • Kang, Won Ku;Park, Yong Soon;Lee, Dong Heum;Kwon, Kwang Il
    • Korean Journal of Clinical Pharmacy
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    • v.8 no.2
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    • pp.122-132
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    • 1998
  • SB-31 which contains Pursatilla, Licoris and Ginseng extracts was recently proved as an anticancer agent. In a preclinical effort to be applied this drug to human, pharmacokinetics of SB-31 was carried out in rats and rabbits. Glycyrrhizin(GZ), a saponin of Licoris was used as a standard ingradient for the pharmacokinetics of SB-31. The rat's blood, bile and urine samples were serially collected in femoral vein, common bile duct and bladder, respectively, after bolus i.v. injection at a dose of 1 or 1/5 ampul/rat and rabbit's blood samples from the marginal ear vein at a dose of 1 or 3 amp./rabbit. GZ and glycyrrhetic acid(GA), a major metabolite of GZ in the physiological samples were analysed by HPLC with UV detection. The decline of GZ in plasma concentration was generally biexponential at each dose. GZ was almost completely recovered in bile within 18 hour. GA wasn't detected in the samples with UV detector. In the rat, Vss and Kel at a dose of 1 and 1/5 ampul of SB-31 were $98.06\pm6.07\;ml,\;0.33\pm0.05\;hr^{-1}\;and\;65.46\pm11.19\;ml,\;0.68\pm0.25\;hr^{-1}$, respectively. Those in rabbits at a dose of 3 and 1 ampul of SB-31 were $235.24\pm30.72\;ml,\;0.13\pm0.36\;hr^{-1}\;and\;341.32\pm28.58\;ml,\;0.27\pm0.04\;hr^{-1}$, respectively. 'WinNonlin' was utilized for the compartmental analysis. A two-compartment model was chosen as the most appropriate pbarmaco-kinetic model. The data were best described by using a weighting factor of $1/y^2$. To evaluate the effect of SB-31 on cardiovascular system, serially diluted SB-31 was directly injected into coronary artery in the isolated perfused rat heart and the effect of PSF, PSH, saponins of Pursatilla, and SB-31 on PT, APTT of healthy human plasma was examined. Except the positive inotropic effect of ten times diluted solution of SB-31, there was no significant effect on LVDP, (- dp/dt)/(+dp/dt), heart rate and coronary flow in comparision with that of vehicle. SB-31 had no effect on PT but slightly delayed APTT about $6.9{\sim}11.5\%$. There was no significant effect of PSF and PSH on PT & APTT. Conclusively, SB-31 did not show any notable toxic effects on cardiovascular system.

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Effect of Ammonia on the Action Potential of the Atrial Muscle and Sinus Node Cells of the Rabbit Heart (암모니아가 가토심방근 및 동방결절세포의 활동전압에 미치는 효과)

  • Cho, Yong-Soo;Kang, Sok-Han;Kim, Jin-Hyuk;Koh, Sang-Don;Kim, Kee-Soon
    • The Korean Journal of Physiology
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    • v.23 no.2
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    • pp.339-350
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    • 1989
  • Electrophysiological effects of ammonia was studied in the isolated superfused sinus node and atrial muscle cells of the rabbit heart. No significant changes were observed in the overshoot potential (05), maximum diastolic potential (MDP), and action potential amplitude (APA) of the sinus node cells following superfusion with 3.0 mM ammonia, fifty times upper limit of the normal human plasma level. However the action potential duration (APD) of sinus node cells were significantly prolonged after superfusion with 0.6 mM ammonia for 20 min or with 1.2 and 3.0 mM ammonia for 5 minutes. Ammonia in all the concentrations tested decreased the rate of spontaneous firing (RSF) from the sinus node cells. After superfusion of sinus node cells with 0.3 mM ammonia for 20 min, the RSF significantly decreased from 20 min to 25 min after onset of superfusion while a significant decrement in the RSF was observed from 7 min to 30 min following superfusion with 3.0 mM ammonia for S min. On the other hand, the effects of ammonia on the action potential of the rabbit atrial muscle cell were much similar to those on pacemaker cells except that the atrial cell was generally less sensitive to ammonia. The results suggest that ammonia may cause changes in the action potential of the rabbit cardiac cells by the direct action, and that the cardiac effects of ammonia are generally opposite to those of glycine.

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Effects of Kimchi Solvent Fractions on Accumulation of Lipids in Heart, Kidney and Lung of Rabbit Fed High Cholesterol Diet (김치 용매획분이 고 콜레스테롤 식이를 섭취한 토끼의 심장, 신장 및 폐의 지질 축적에 미치는 영향)

  • 송영옥;전혜년;권명자
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.5
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    • pp.814-818
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    • 2002
  • The effects of dichloromethane (CH$_2$C1$_2$), ethylacetate (EtOAc) or water ($H_2O$) fraction of Korean cabbage kimhi on accumulation of lipids in the heart, kidney and lung of rabbit fed 1% cholesterol diet for 16 weeks were studied. The amount of kimhi fraction added to the 100 g of diet was 8.3 mg of CHaC12.5.6 W of EtOAc, and 221.9 mg of $H_2O$, which are equivalent to 5% of freeze-dried kimhi added to the diet. Each group had 6 rabbits and rabbit was housed individually. Cholesterol and triglyceride concentrations of three organs were noticeably decreased due to these solvent fractions of kimhi but for phospholipid and total lipids, only CH$_2$C1$_2$ fraction group showed decreasing effects. In the heart, compared to the control, cholesterol concentrations for CE$_2$C1$_2$, EtOAc, and H2O fraction group were decreased by 42 (P<0.05),21 (P<0.05), and 8%, respectively, and triglyceride for these groups were decreased by 29 (p<0.05),4, and 11%, respectively. In kidney, cholesterol concentration for CH$_2$C1$_2$, EtOAc, and H2O fraction group were decreased by 23, 12, and 11%, respectively (p<0.05) and triglyceride concentration for CH$_2$Cl$_2$ and H2O fraction groups were significantly decreased by 51 and 21%, respectively (p<0.05). In lung, cholesterol concentrations for CItCIB, EtOAc, and H2O fraction groups were decreased by 37,20, and 22%, respectively (p<0.05) and triglyceride concentration of these groups were significantly decreased by 39, 28, and 28%, respectively (p<0.05). And phospholipid and total lipid of CH$_2$CI$_2$ fraction group were significantly decreased by 33 and 34% respectively (p<0.05). Among three organs the cholesterol content of lung was the highest followed kidney and heart. For triglyceride, heart, kidney and lung is in the order of showing the highest concentration. The phospholipid concentration was not significantly different among three organs. According to these results, we may conclude that CH$_2$C1$_2$, fraction of kimhi might have the most active component, which decreases cholesterol, triglyceride, phospholipid and total lipids concentrations in heart, kidney, and lung of rabbit fed high cholesterol diet.

Pharmacological Studies of Plantaginis Semen (차전자(車前子)(질경이)의 약리학적(藥理學的) 연구(硏究))

  • Ko, Suk-Tai;Lim, Dong-Yoon
    • Journal of Pharmaceutical Investigation
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    • v.7 no.1_4
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    • pp.28-37
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    • 1977
  • The pharmacological actions to methanol extract(PME) obtained from Plantaginis semen were examined in the rabbit. 1) PME, when administered into the vein of rabbit, produced the fall of blood pressure and stimulation of respiration. The former action was inhibited by atropine but the latter not affected by atropine. 2) PME caused contraction in both isolated intestinal and uterus strips, atropine blocked the contraction of intestinal strips while did not the uterus contraction. 3) PME decreased the heart rate of rabbit anesthetized with urethane. 4) PME elicited antidiuresis with doses ranging from 10mg/kg. The antidiuresis appeared to be related to the hemodynamic changes decreases in the renal plasma flow and glomerular filtration rate. Urinary sodium and potassium decrease in the renal plasma flow and glomerular filtration rate. Urinary sodium and potassium decrease in relation to the diminished filtration.

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Studies on the Components of Umbelliferous Plants in Korea(IX) Pharmacological Study of Isoimperatorin and Oxypeucedanin (한국산산형과식물의 성분연구 IX Isoimperatorin 및 Oxypeucedanin의 일선약리작용)

  • 지형준;김학성
    • YAKHAK HOEJI
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    • v.14 no.1_2
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    • pp.21-27
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    • 1970
  • Isoimperatorin and Oxypeucedanin isolated from root of Angelica Koreana Max. (Umbelliferae) that is used as "Kang-Whal" a botanical drug, in Korea, Show following general pharmacologic activities. The treatment with Oxypeucedanin on the exercised duodenum of the rabbit increased the motility of it while isoimperatorin shows little effects. But on the exercised heart of the frogs, both components depressed its contractility. Whereas Oxypeucedanin depressed both blood pressure of the carotied artery and respiration of the rabbit, Isoimperatorin tends to increase blood pressure, respiration and the tonus of the muscle of the earth worm. Oxypeucedanin did not affect the tonus of the muscles of the earth worm, but depressed the uterus contraction of the rabbit, which was, on the contrary, increased by Isoimperatorin.

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Studies on the Components of Umbelliferae Plants in Korea -Pharmacological Study of Decursin, Decursinol and Nodakenin- (한국산 산형과 식물의 성분연구 -Decursin, Decursinol 및 Nodakenin 의 일반약리작용-)

  • Chi, Hyung-Joon;Kim, Hak-Sung
    • Korean Journal of Pharmacognosy
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    • v.1 no.1
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    • pp.25-32
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    • 1970
  • Decursin, decursinol and nodakenin which were isolated from the root of Angelica gigas $N_{AKAI}$ (Umbelliferae) that is used as a botanical drug Dang-Gui (當歸) in Korea show following general pharmacologic activities. Decursin and decursinol increased the motility of the excised duodenum of the rabbit, but nodakenin did not. All of these three compounds depressed the heart contraction of the frog and blood pressure of the carotid artery and respiration of the rabbit. Decursin increased uterus contraction of the rabbit, but decursinol depressed it. And the tonus of the muscle of the earth worm was increased by decursinol, but was decreased by decursin.

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Effects of Kimchi Solvent Fractions on Anti-oxidative Enzyme Activities of Heart, Kidney and Lung of Rabbit Fed a High Cholesterol Diet (김치 용매획분이 고 콜레스테롤 식이를 섭취한 토끼의 심장, 신장 및 폐의 항산화 효소계 활성에 미치는 영향)

  • 전혜년;김현주;송영옥
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.32 no.2
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    • pp.250-255
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    • 2003
  • The effects of dichlorornethane (CH$_2$C$_2$), ethylacetate (EtOAc) or water ($H_2O$) fraction of Korean cabbage kimchi on anti-oxidative enzyme activities of the heart, kidney and lung of rabbit fed 1% cholesterol diet for 16 weeks were studied. The amount of kimchi fraction added to the 100 g of diet was 8.3 mg of CH$_2$C1$_2$,5.6mg of EtOAc, and 221.9 mg of $H_2O$, which are equivalent to 5% of freeze-dried kimchi in the diet. Each group had 6 rabbits and rabbit was housed individually. Lipid peroxide values for the heart was the highest followed by lung and kidney. But the activities of catalase and GSH-px were the lowest in the heart and the highest in the kidney. Activities of anti -oxidative enzymes (catalase, GSH-px, Mn-SOD, Cu, Zn-SOD) of rabbits fed kimhi solvent fractions added diets were lower than those of the control which fed 1% cholesterol diet. Among kimchi groups, CH$_2$Cl$_2$ group showed the lowest (p<0.05) enzymes activities. Lipid accumulation in these organs fed diets with kimchi solvent fractions, especially with CH$_2$C1$_2$fraction, were lower than that of the control. Therefore, production of the lipid free radicals might be suppressed and the activities of anti -oxidative enzymes responsible for removing the free radicals seemed to be lowered in kimch frachoin-fed rabbits.

Hypotensive Action of Coptis Rhizoma in Rabbit (황련성분의 혈압하강 작용)

  • Kwak I.S.;Lee S.B.;Cho B.H.;Cho K.C.
    • The Korean Journal of Pharmacology
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    • v.12 no.2 s.20
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    • pp.61-65
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    • 1976
  • Coptis rhizoma had been applied in the chines medicine as well as in the folk remidies and it was advocated that coptis rhizoma exerts good therapeutic effect in some case of alimentary disorders and other hypotensive ailments. However the basic pharmacology and the mechanism of hypotensive action are not clear. This experiment was carried out in order to reevaluate the pharmacology, especially hypotensive action of coptis rhizoma and to clarify the mechanism of action, in the rabbits and also $LD_{50}$ of coptis rhizoma was determined using mice as experimental animals. The results of the experiment were as follows. 1) $LD_{50}$ to the mice was 69 mg/kg. 2) Blood pressure manifested gradual responses by the fall of -17, -26, -62 mmHg in proportion to the administration of 3, 5, 10 mg/kg of coptis rhizoma extract respectively. 3) No significant differance was observed in heart rate between the normal control group and the coptis rhizoma extract treated group. 4) Administration of coptis rhizoma extract 5 mg/kg to the rabbit pretreated with atropine or avil did not show any significant difference in the blood pressure compared with that of control group. 5) In the rabbit pretreated with coptis rhizoma extract 5mg/kg, the hypotensive effect of epinephrine was significantly inhibited in comparison with that of normal rabbit.

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The Effect of Bone Marrow-Derived Osteoblasts on Mandibular Deffect in Rabbit (가토골수에서 유래된 골모세포의 하악골 결손부 이식시 골형성에 미치는 효과)

  • Park, Young-Ju;Nam, Jeong-Hun;Kim, Bo-Gyun;Jeon, Min-Su;Chung, Jae-An;Lee, Jung-Won;Ahn, Jang-Hoon;Gang, Tae-In;Park, Mi-Hee;Lim, Sung-Chul
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.32 no.4
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    • pp.306-312
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    • 2010
  • Purpose: The purpose of this experiment was to evaluate the clinical effect of cultured autoglogous osteoblasts as a way to treat the defect of mandible in rabbits. Materials and Methods: Twelve rabbits were used to determine the rate of osteogenesis. The osteoblasts were obtained from the iliac crest of rabbits using aspiration. They were then cultured in Dulbecco's Modified Eagles's Medium (DMEM) with beta-glycerophosophatate, L-ascorbicacid, and dexamethasone to proliferate and differentiate osteoprogenitor cells. The expression of osteogenic markers were detected by reverse transcription-polymerase chain reaction (RT-PCR) and silver nitrate staining techniques. Five, 10-mm holes were placed in each rabbit mandible to simulate defective regions with the use of a low speed trephine bur. In the experimental group, the previously cited defects were grafted with both activated osteoblastic and autogenous bone. The control group, however, was only grafted with autogenous bone. Both groups were then analyzed at 2, 4, and 8-week intervals using bone histomorphometric analysis. Results: According to histomorphologic analysis, the rates of new bone formation at the 2, 4, and 8-week intervals were 36%, 51%, and 23% for the control group, respectively; 52%, 39%, and 28%, for the experimental group, respectively. The experimental group showed higher rates of new bone formation compared to the control group at both the 2-week and 8-week interval. Conclusion: Bone marrow-derived osteoblasts seems to be a promising bone graft material.

Influence of Dichloroisoproterenol and Panax Ginseng on the action of some drugs. (Dichloroisoproterenol및 인삼(人蔘)의 이삼약물(二三藥物)의 작용(作用)에 미치는 영향(影響))

  • Chun, Yun-Sook;Choi, Baik-Hi;Kim, Chi-Euk;Lim, Kyu-Bok;Choi, Kyung-Hun
    • The Korean Journal of Pharmacology
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    • v.2 no.1 s.2
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    • pp.21-29
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    • 1966
  • Dichloroisoproterenol(DCI) i; one of the well known ${\beta}$-adrenergic receptor blocking agents. According to Moran and Perkins, DCI has sympathomimetic like action in relatively low concentrations. Fleming and Hawkins confirmed that DCI acts upon the receptors concerned with positive chronotropic and inotropic actions in the heart. Vogins reported that DCI, in concentration of $5{\times}10^{-8}$ to $5{\times}10^{-6}g/ml$, had properties of sympathomimetic amine causing positive inotropic and chronotropic actions in normal rat atria. And James and Nadeau found that DCI had not only adrenergic blocking effect in moderate and higher concentrations, but it also blocked the effect on the sinus node by vagal stimulation and of directly administered acetylcholine in higher concentrations. As stated above by many authors, DCI has complicated actions according to its concentrations. Our aim at the present experiments was to study the effects of DCI to the action of ouabain and acetylcholine upon the excised rabbit atria, as well as to the action of barium chloride and acetylcholine upon the excised rabbit intestine. In addition, Pan ax Ginseng is widely used as tonics in oriental nations, its pharmacological action, however, has not been clearly established. So we atempted to investigate the effects of the water extract of Panax Ginseng to the action of ouabain and DCI upon both atria and intestine. The results obtained were as follows. 1) DCI has a negative inotropic effect on the excised rabbit atria at concentration of $10^{-5}$ and a positive inotropic effect at concentration of $10^{-6}$. 2) DCI (at concentration of $10^{-6}$) potentiates the positive inotropic effect of ouabain upon the excised rabbit atria. 3) DCI antagonizes the action of acetylcholine upon the excised rabbit atria. 4) The water extract of Panax Ginseng, at concentration of $10^{-3}$, decreases the contractile force of rabbit atria, and tends to slightly increase that of rabbit atria at $10^{-4}$. 5) The water extract of Panax Ginseng exhibits a synergistic action with ouabain on the contractile force of rabbit atria. 6) DCI, in concentrations of $10^{-7}{\sim}10^{-6}$, depresses the tone and amplitude of contraction of the excised rabbit intestine. The depression of the intestinal tone markedly appears in pretreatment with reserpine 2mg/kg 24 hours. 7) DCI antagonizes the contractile effect of barium chloride on the excised rabbit atria. 8) DCI has no significant influence on the action of acetylcholine upon the excised rabbit intestine. 9) The series of those evidences indicates that DCI has a sympathomimetic-like action and more over a relaxing action directly on the excised rabbit intestine. 10) The water extract of Panax Ginseng in concentrations of $10^{-4}{\sim}10^{-3}$, has transient depression of the intestinal tone, but later gradually recovers its normal motility: 11) The water extract of Panax Ginseng has a synergistic action with ouabain on the intestinal contractility.

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