• Title/Summary/Keyword: Isolated rat heart

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Cardioprotective and Antihypertensive Effects of KR-31281, KR-31282 and KR-31299, Newly Synthesized $K_{ATP}$ Openers, in Conscious Rats and Isolated Ischemic Rat Hearts (신규 합성 $K_{ATP}$ 통로 개방제인 KR-31281, KR-31282 및 KR-31299의 흰쥐 적출 허혈 심장 및 비마취 흰쥐에 대한 심장보호 및 혈압강하 작용)

  • Lee, Sun-Sook;Yun, Yeo-Pyo;Shin, Hwa-Sup
    • 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.

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Pharmacological Actions of New Wonbang Woohwangchungsimwon Pill on Cardiovascular System (신원방우황청심원의 심혈관계에 관한 약효)

  • 조태순;이선미;김낙두;허인회;안형수;권광일;박석기;김상호;신대희
    • YAKHAK HOEJI
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    • v.43 no.2
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    • pp.237-250
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    • 1999
  • In order to investigate the pharmacologic properties of New Wonbang Woohwangchungsimwon Pill(NSCH), effects of Wonbang Woohwangchungsimwon Pill (SCH) and NSCH were compared using various experimental models. In rat aorta, NSCH and SCH made the relaxation of blood vessels in maximum contractile response to phenylephrine (10-6 M) regardless to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not affect significantly the relaxing effects of NSCH and SCH. NSCH and SCH inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCH and SCH decreased significantly heart rate. These, at high doses, had a negative inotropic effects that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In guinea-pig papillary muscle, these had no effects on parameters of action potential such as action potential amplitude (APA), $V_{max}$ and resting membrane potential (RMP) at low doses, whereas inhibitory the cardiac contractility at high doses. Furthermore, these had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These results suggest that NSCH and SCH have weak cardiovascular effects, and that there is no significant differences between cardiovascular effects of two preparations.

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Effects of Verapamil in Cardioplegic Perfusates on the Ischemic Myocardium in Isolated Rat Heart (흰쥐의 적출된 심장에서 Verapamil이 허혈성 심근에 미치는 효과)

  • Kim, Su-Cheol;Jo, Gyu-Seok;Park, Ju-Cheol;Yu, Se-Yeong
    • Journal of Chest Surgery
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    • v.30 no.2
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    • pp.119-124
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    • 1997
  • Using isolated rat heart preparations, we observed the protective effe ts of verapamil cardioplegia on ischemic myocardial injury. Isolated rat hearts were subjected to global ischemia at $25^{\circ}C$ Twenty four isolated Sprague Dawley rat hearts underwent 30 minutes of the retrograde nonworking perfusion with Krebs-Henseleit buffer solution followed by $25^{\circ}C$ cardioplegic solution (St. Thomas'Hospital Cardioplegic Solution) for 60 minutes. Before ischemic arrest, rat hearts were treated with cold cardioplegic solution in control group (n=12) and cold cardioplegic solution with verapamil (1 mg/L) in experimental group (n=12). After 60 minutes of ischemia, hemodynamic and biochemical parameters such as heart rate, left ventricular pressure (LVP), + dp/dt max, coronary flow and creatine phosphokinase (CPK) were measured before giving cardioplegia and 30 minutes after reperfusion. Verapamil group exhibited greater recovery of heart rate, LVP, +dpldt max, coronary flow and CPK than control group (p < 0.05).

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Cardioprotective Effect of the Mixture of Ginsenoside Rg3 and CK on Contractile Dysfunction of Ischemic Heart

  • Kim, Jong-Hoon
    • 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.

Study on the Effect of Ginseng on the cyclic AMP Content in the Rat Hearts (인삼(人蔘)이 백서심장(白鼠心臟)의 cyclic AMP함량(含量) 변화(變化)에 미치는 영향(影響)에 관(關)한 연구(硏究))

  • Kim, Nak-Doo;Cha, Soo-Man
    • Korean Journal of Pharmacognosy
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    • v.13 no.4
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    • pp.137-144
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    • 1982
  • It was previously reported from our laboratory that the rate of deterioration of the force of contraction was slower in heart from Panax ginseng extract treated rats. The study carried out to elucidate its mechanism of the action on hearts. The cyclic AMP content in the rat hearts was measured by the method of radioimmunoassay techniques. Panax ginseng extract (100mg/kg/day) was administered orally to male Sprague-Dawley rats weighing 150g to 250g for 1 week and after 24 hrs the hearts were isolated and the cyclic AMP content in the fresh heart was assayed. The difference in cyclic AMP content between the rats treated with Panax ginseng extracts and normal rats was not significant. Panax ginseng extract(l00mg/kg/day) was administered orally to the rats for I week and after 24 hrs the hearts were isolated and perfused with Krebs-Henseleit buffer (pH7.4) for 90min. The cyclic AMP content in the both treated and normal rats was not also significantly different. On the other hand, when total ginseng saponin (50mg/kg/day) was administered orally to rats for 1 week and after 24 hrs, the isolated hearts were perfused with Krebs Henseleit solution for 32min, the cyclic AMP content in total ginseng soponin treated hearts was decreased by 18.7% compared to normal rats. It was also observed that when isolated hearts were perfused with total ginseng saponin $(10^{-4}g/ml)$ for 12 min after 30 min equilibration period, the cyclic AMP content in total ginseng saponin treated hearts was decreased by 23.7% compared to normal rats. Isolated hearts were perfused with ginseng saponins $(10^{-4}g/ml)$ or with Krebs-Henseleit solution alone for 10min and subsequently with dl-isoproterenol $(1/2{\times}10^{-6}M)$ until the positive inotropic effect of isoproterenol was initiated. The cyclic AMP content in each rat hearts treated with total ginseng saponin, or with ginsenoside $Rb_1$, or with Krebs-Henseleit solution alone were increased by 35.5%, 42.4%, 47.5%, respectively, compared to normal rats.

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Protective Effect on the Rat's Myocardium with Changes in Magnesium Concentrations (마그네슘 농도변화에 따른 흰쥐의 심근 보호효과)

  • Hong, Chi-Uk;Jo, Gyu-Seok;Yu, Se-Yeong
    • Journal of Chest Surgery
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    • v.30 no.1
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    • pp.11-16
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    • 1997
  • The Increasing use of coronary perfusates for the protection of the human heart during ischemic cardiac arrest has placed great emphasis on the need for a rational and safe formulation. For the purpose of this study isolated rat hearts were connected to retrograde nonworking perfusion system proposed by Langendorff, and then perfused for 20 minutes by coronary infusates of magnesium concentration of 1.66 m Mol per liter(group A, n: 10) or 15mMo1 per liter(group B, n: 10). After 20 minutes perfusion, cold cardioplegic solution (modified St. Thomas'Hospital solution) was infused for 2 minutes, and prepared within 4$^{\circ}C$ Krebs-Henseleit solution. Finally, 20 minutes of cononay reprsfuslon was reestablished after I hour of cold ischemic cardiac arrest. Hemodynamic parameters (heart rate, left ventricular pressure, $\pm$ dp/dt max. and coronany flow) and enzymes assay (creatine phosphokinase, lactic dehydrogenase and flutamic oxaloacetic transaminase) were performed each other at whic rat heart was perfused for 20 minutes and reperfused for 20 minutes thereafter. There were significant differences in the recovery rate of heart rate, systolic left ventricular pressure, + dp/dt max, and coronary flow and reperfusion-perfusion ratio of creatine phosphokinase(P < 0.05). But, there were no signicant differences in the recovery rate of dp/dt max, and reperfunion-perfusion ratio of lactic dehydrogenase and glutamic oxaloacetic acid (P > 0.05).

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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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Involvement of Adenosine in Cardioprotective Effect of Catecholamine Preconditioning in Ischemia-Reperfused Heart of Rat

  • Kim, Young-Hoon;Kim, Chan-Hyung;Kim, Gi-Tae;Kim, In-Kyu;Park, Jong-Wan;Kim, Myung-Suk
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.6
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    • pp.753-761
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    • 1998
  • Preconditioning of a heart with small doses of catecholamines induces a tolerance against the subsequent lethal ischemia. The present study was performed to find a specific receptor pathway involved with the catecholamine preconditioning and to test if adenosine plays a role in this cardioprotective effect. Isolated rat hearts, pretreated with small doses of ${\alpha}-\;or\;{\beta}-adrenergic$ agonists/antagonists, were subjected to 20 minutes ischemia and 20 minutes reperfusion by Langendorff perfusion method. Cardiac mechanical functions, lactate dehydrogenase and adenosine release from the hearts were measured before and after the drug treatments and ischemia. In another series of experiments, adenosine $A_1\;or\;A_2$ receptor blockers were treated prior to administration of adrenergic agonists. Pretreatments of a ${\beta}-agonist,\;isoproterenol(10^{-9}{\sim}10^{-7}\;M)$ markedly improved the post-ischemic mechanical function and reduced the lactate dehydrogenase release. Similar cardioprotective effect was observed with an ?-agonist, phenylephrine pretreatment, but much higher $concentration(10^{-4}\;M)$ was needed to achieve the same degree of cardioprotection. The cardioprotective effects of isoproterenol and phenylephrine pretreatments were blocked by a ${\beta}_1-adrenergic$ receptor antagonist, atenolol, but not by an ${\alpha}_1-antagonist,$ prazosin. Adenosine release from the heart was increased by isoproterenol, and the increase was also blocked by atenolol, but not by prazosin. A selective $A_1-adenosine$ receptor antagonist, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) blocked the cardioprotection by isoproterenol pretreatment. These results suggest that catecholamine pretreatment protects rat myocardium against ischemia and reperfusion injury by mediation of ${\beta}_1-adrenergic$ receptor pathway, and that adenosine is involved in this cardioprotective effect.

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The Effect of Cyclosporine A on the Expression of the Major Histocompatibility Complex Antigen Class II(MHC II) (Cyclosporine A의 MHC Class II 항원에 대한 억제 효과)

  • 박국양
    • 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.

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Protective Effect of Chlorpromazine for the Isolated Rat Heart from Reperfusion Injury (Chlorpromazine 이 과분극 정지심장의 재관류 손상에 미치는 보호효과)

  • 류한영
    • 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.

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