• Title/Summary/Keyword: Isolated perfused rat heart

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The Effect of Additives in the Cardioplegic Solution on the Recovery of Myocardium, Compariosn Among Albumin, Mannitol, and Glucose (심마비용액의 삼투압을 유지하기위한 첨가 물질들의 차이가 심근보호에 미치는 영향)

  • Kim, Eun-Gi;Lee, Jong-Guk;Lee, Sang-Heon
    • Journal of Chest Surgery
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    • v.24 no.11
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    • pp.1058-1067
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    • 1991
  • High potassium cardioplegia is a widely accepted procedure to enhance myocardial protection from ischemic injuries associated with open heart surgery. Maintaining optimum osmolarity of the cardioplegic solution is one of the required conditions for an ideal cardioplegic solution Albumin is an frequently added component for maintaining optimum osmolarity of clinically used cardioplegic solutions. But the source of albumin is human blood so that the supply is limited and the cost of manufacturing is relatively high. Recently there are moves to minimized the use of blood product for fear of blood-associated infections or immunological disorders. In this experiment, we substituted mannitol or glucose for albumin added to the cardioplegic solution which has been used at the Wonju Medical College, To determine whether addition of mannitol or glucose instead of albumin in the cardioplegic solution can produce satisfactory myocardial protection during ischemia, three different groups of isolated rat heart perfused by modified Langendorff technique were studied. Wonju Cardioplegic Solution was selected as a standard high potassium[18mEq/L of K+] cardioplegic solution. Three kinds of cardioplegic solution were made by modifying the composition maintaining the same osmolarity[339$\pm$1mOsm/Kg] Isolated rat heart were perfused initially with retrograde nonworking mode and then changed to working mode. After measuring the heart rate, systolic aortic pressure, aortic flow, coronary flow, ischemic arrest by aorta cross clamp and cardioplegia was made maintaining the temperature of water jacket at 10oC. The heart was rewarmed and reperfused after 60min of ischemic arrest with intermittent cardioplegia at the 30min interval. The time to return of heart beat and the time required to get. Regular heart beat were observed after reperfusion. The recovery rate of the functional variables-heart rate, systolic aortic pressure, aortic flow, coronary flow and cardiac output were calculated and compared among the three groups of different cardioplegia-albumin, mannitol, and glucose. The wet weight and dry weight was measured and the water content of the heart as figured out for comparison. The time to return of heart beat was fastest in the albumin group, The functional recovery rates were best in the albumin group also. In the above conditions, albumin was the best additive to the cardioplegic solution compared to the mannitol or glucose.

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The Effect of Ginseng on Heart Contraction and Sarcoplasmic Reticulum Function(I) -The Effect of Ginseng on the Myocardial Contractility and Force-Velocity Curves of Papillary Muscles from Rats (인삼이 심장 수축력과 소포체 기능에 미치는 영향(제1보) -흰쥐 심장의 수축력 및 유두근의 Force-Velocity 곡선에 대한 인삼성분의 효과-)

  • 오우택;김낙두
    • YAKHAK HOEJI
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    • v.27 no.2
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    • pp.155-161
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    • 1983
  • The rates of deterioration of contractile forces of isolated hearts from ginseng component treated rats were determined. Rat papillary muscles were also used to study the influence of ginseng on the mechanical performance of heart. Rats weighing 200-300g were administered orally with ginseng ethanol extract (100mg/kg/day), ginseng total saponin (50mg/kg/day) and ginsenoside Rbl (5mg/kg/ day) for a week respectively. The isolated hearts from rats were perfused with Krebs-Henseleit solution by Langendorff perfusion apparatus. The force-velocity relation was clearly seen with the load-generator equipped isotonic shortening recording apparatus. The control group was only able to maintain 60% of their initial contractile forces after 120 minutes of perfusion, whereas ginseng ethanol extract treated group was able to sustain nearly their initial strength even after 120 minutes of perfusion. The similar effects were seen in the hearts treated with total ginseng saponin and ginsenoside Rb$_{1}$. Ginseng ethanol extract did alter mechanical performance of rat ventricular myocardium. It increased both maximum velocity(Vmax) of isotonic shortening and isometric force (P$_{0}$) and showed increased velocity of shortening significantly (P<0,05) at any one afterload.d.

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Experimental Studies on the Effect of Ginsenoside Rg1 Mixtures in an Isolated Rat Heart after Ischemic Arrest and Reperfusion (흰 쥐 적출 심장에서 비작업성 관류 회로를 이용한 인삼 성분 Ginsenoside Rg1 Mixtures의 심근 보호 효과에 관한 실험적 연구)

  • 김동원;신원선;이재영;김범식;조규석;유세영
    • Journal of Chest Surgery
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    • v.31 no.6
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    • pp.567-575
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    • 1998
  • Panax Ginseng C.A. Meyer has been known for hundreds of years as the most valuable drug having mysterious effects among all the herbal medicines and plants in Korea. Also, many experimental studies have been performed recently that the various effects were identified and applied clinically. So we attempted an experimental study on the effect of ginsenoside Rg1 mixtures in an isolated rat heart with the use of the Langendorff model. The objective of this study was to determine whether this ginsenoside Rg1 mixtures would protect the myocardial injury after ischemic arrest and reperfusion. Isolated rat hearts were allowed to equilibrate for 20 minutes and were then subjected to 15 minutes of normothermic ischemia. After this ischemic period, isolated rat hearts were allowed to reperfusion for 10 minutes(Ischemic Group). In other group , isolated rat hearts were perfused for 60 minutes continuously with normothermia( Normothermic Group). Hemodynamic and biochemical parameters such as heart rate, left ventricular pressure, +dp/dt max, coronary blood flow and cardiac enzymes were measured during initial perfusion, ischemia, reperfusion period (Ischemic group) and 20, 40 and 60 minutes after continuous perfusion(Normothermic group). After completion of the experiment, this data was evaluated and the following results were obtained. 1. Heart rates showed an increase in both ischemic and normothermic experimental groups, but statistically significant differences were not identified. 2. LVP(Left Ventricular Pressure) showed statistically significant differences in both ischemic and normothermic experimental groups(p<0.005, p<0.01). 3. +dp/dt max showed statistically significant differences in both ischemic and normothermic experimental groups(p<0.01, p<0.01). 4. There were no statistically significant differences in coronary blood flow and cardiac cenzymes in all groups, but experimental groups seemed to have better protection and recovery. These results suggest that ginsenoside Rg1 mixtures has a protective effect on the myocardial injury after ischemia and reperfusion.

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Role of Calcium in Reperfusion Damage of Ischemic Myocardium; Influence on Oxygen Radical Production

  • Park, Jong-Wan;Kim, Myung-Suk;Park, Chan-Woong
    • Toxicological Research
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    • v.4 no.1
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    • pp.23-35
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    • 1988
  • The role of calcium in the production of oxygen radical which causes reperfusion damage of ischemic heart has been examined. The reperfusion damage was indrced in isolated Langendorff perfused rat hearts by aortic clamping for 60 min followed by reperfusion with oxygenated Krebs-Henseleit solution with or without 1.25 mM $CaCl_2.$ On reperfusion of the ischemic hearts with the calcium containing solution, the release of cytosolic enzymes (LDH and CPK) increased abruptly. These increased release of enzymes were significantly inhibited by additions of oxygen radical scavengers (SOD, 5,000 U; catalase, 12,500 U) into the reperfusion solution. In the hearts isolated from rats pretreated with allopurinol(20 mg/kg orally, 24 hr and 2 hr prior to the experiments), the levels of enzymes being released during reperfusion were significantly lower than that of the control. However, in the hearts perfused with the calcium-free but oxygenated solution, the increase in the release of cytosolic enzymes during reperfusion was neither inhibited by oxygen radical scavengers nor by allopurinol pretreatment. For providing the evidence of oxygen radical generation during the reperfusion of ischemic hearts in situ, the SOD-inhibitable reduction of exogenously administered ferricytochrome C was measured. In the hearts perfused with the calcium containing solution, the SOD-inhibitable ferricytochrome C reduction increased within the first minute of reperfusion, and was almost completely inhibited by allopurinol pretreatment. When the heart was perfused with the calcium free solution, however, the reduction of ferricytochrome C was not only less than that in the calcium containing condition, but also was not so completely inhibited by allopurinol pretreatment. By ischemia, xanthine oxidase (XOD) in the ventricular tissue was changed qualitatively, but not quantitatively. In the heart made ischemic with the calcium containing condition, the oxygen radical producing O-form of XOD increased, while the D- and D/O-form decreased. However, in the ischemic heart reperfused with the calcium free condition, the D/O-form of XOD was elevated without significant increase in O-form of the enzyme. It is suggested from these results that the calclum may play a contributing role in the genesis of reperfusion damage by promoting the conversion of xanthine oxidase from the D/O-form to the oxygen radical producing O-form in the ischemic myocardium.

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Myocardial Protective Effect of Adenosine in Ischemic Rat Heart (흰쥐의 허혈심장에서의 Adenosine의 심근 보호 효과에 관한 연구)

  • 박승규
    • Journal of Chest Surgery
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    • v.23 no.6
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    • pp.1090-1106
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    • 1990
  • This study was undertaken to investigate whether adenosine administered during cardioplegic arrest could enhance myocardial protection and improve recovery of function after ischemia. Isolated Langendorff-perfused rat hearts were subjected to 40 minutes of normothermic [37oC] ischemia. Control hearts [n=10] received modified St. Thomas’ cardioplegic solution, and the remaining hearts received modified St. Thomas’ cardioplegic solution with either 20 \ulcornerM [n=10], 200 \ulcornerM [n=10] adenosine. After ischemia of 40 minutes and 30 minutes of reperfusion, left ventricular contractility was superior in all groups of adenosine-treated hearts compared with control hearts. Furthermore, there was a significant incremental increase in functional recovery with increasing dose of adenosine. Post-ischemic diastolic stiffness was significantly better in all adenosine groups compared with controls. No differences were noted in coronary flow or myocardial water content between adenosine-treated and control hearts. These data demonstrate that adenosine administered in these concentrations provides myocardial protection, preservation of myocardial ATP and creatine phosphokinase and improved post-ischemic functional hemodynamic recovery after normothermic ischemia, presumably metabolically by reducing depletion of adenosine triphosphate, inducing rapid cardiac arrest and enabling improved post-ischemic recovery.

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Effect of Drugs on the Cardiac Transport, Metabolism and Action of Idarubicin: Pharmacokinetic and Pharmacodynamic Modeling

  • Kang, Won-Ku
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.212-213
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    • 2002
  • Using the isolated perfused rat heart this study investigated 1) the cardiac uptake of idarubicin (IDA), 2) the role of P-glycoprotein (P-gp) in the uptake process, 3) the formation of IDOL from IDA in the heart, and 4) the effect of P-gp inhibitors (verapamil, amiodarone, PSC 833), doxorubicin, hypothermia, xanthine derivatives (caffeine, theophylline) and metabolism inhibitors (rutin, phenobarbital) on the pharmacokinetics and pharmacodynamics of IDA using a mathematical modeling approach. A minimal model was constructed; the differential equations were numerically solved and fitted to the data using the ADAPT II-software package using maximum likelihood estimation assuming that the measurement error has a standard deviation which is a linear function of the measured quantity[1]. (omitted)

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Myogenic Autoregulation of Coronary Vessels and Heterometric Autoregulation of the Myocardium

  • Doring, H.J.;Schlicht, I.;Hiller, V.;Jiang, X.R.
    • The Korean Journal of Physiology
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    • v.23 no.2
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    • pp.225-236
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    • 1989
  • 1) At the isolated perfused guinea-pig and rat heart heterometric autoregulation of the myocardium and myogenic autoregulation of the coronary vessels were induced by means of stepwise increases of perfusion pressure. 2) According to this loading test Frank-Starling function curves of the left ventricle and pressure-flow curves of the coronary vessels can be drawn. This graphic evaluation gives more information about the condition of the heart and the coronary vessels than simple evaluation under hemodynamic equilibrium. 3) There are significant differences in both curves between animal species and between different perfusate Mg concentration. 4) Myogenic autoregulation is not affected by the cyclooxygenase inhibitors indometacin and me- clofenamate. Thus it appears unlikely that prostanoides are involved in myogenic autoregulation. 5) Ca antagonists (Gallopamil, prenylamine) depress myogenic autoregulation dose-dependently. Enhanced myogenic autoregulation, induced by low extracellular magnesium, can be reduced effectively by Gallopamil. 6) Ginsenosides from Panax ginseng as well as the ginsenoside 'Rg' are effective inhibitors of myogenic autoregulation without major negative inotropic effects.

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The Protective Effect of Epigallocatechin-3 Gallate on Ischemia/Reperfusion Injury in Isolated Rat Hearts: An ex vivo Approach

  • Piao, Cheng Shi;Kim, Do-Sung;Ha, Ki-Chan;Kim, Hyung-Ryong;Chae, Han-Jung;Chae, Soo-Wan
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.5
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    • pp.259-266
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    • 2011
  • The aim of this study was to evaluate the preventive role of epigallocatechin-3 gallate (EGCG, a derivative of green tea) in ischemia/reperfusion (I/R) injury of isolated rat hearts. It has been suggested that EGCG has beneficial health effects, including prevention of cancer and heart disease, and it is also a potent antioxidant. Rat hearts were subjected to 20 min of normoxia, 20 min of zero-flow ischemia and then 50 min of reperfusion. EGCG was perfused 10 min before ischemia and during the whole reperfusion period. EGCG significantly increased left ventricular developed pressure (LVDP) and increased maximum positive and negative dP/dt (+/-dP/dtmax). EGCG also significantly increased the coronary flow (CF) at baseline before ischemia and at the onset of the reperfusion period. Moreover, EGCG decreased left ventricular end diastolic pressure (LVEDP). This study showed that lipid peroxydation was inhibited and Mn-SOD and catalase expressions were increased in the presence of EGCG. In addition, EGCG increased levels of Bcl-2, Mn-superoxide dismutase (SOD), and catalase expression and decreased levels of Bax and increased the ratio of Bcl-2/Bax in isolated rat hearts. Cleaved caspase-3 was decreased after EGCG treatment. EGCG markedly decreased the infarct size while attenuating the increase in lactate dehydrogenase (LDH) levels in the effluent. In summary, we suggest that EGCG has a protective effect on I/R-associated hemodynamic alteration and injury by acting as an antioxidant and anti-apoptotic agent in one.

Effect of Strontium on Norepinephrine Induced Positive Intoropic Effect of Isolated Perfused Rat Hearts (흰쥐 적출심장의 Norepinephrine 유발 양성 변력성작용에 미치는 Strontium의 영향)

  • Kwon, Oh-Cheal;Lee, Kwang-Youn
    • Journal of Yeungnam Medical Science
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    • v.5 no.2
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    • pp.59-69
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    • 1988
  • This study was designed to investigate the effect of substitution of strontium for calcium on mechanical activity in isolated perfused spontaneously beating rat hearts. The mechanical activity of the hearts of Langendorff's preparation in conditions of low calcium and strontium-substitution for calcium was compared. The effect of norepinephrine and verapamil were also observed in those conditions. The results were as follows : 1. In low calcium, the mechanical activity of the heart preparation was significantly reduced, but when the equimolar strontium was substituted for the reduced calcium, the activity was kept at similar level to the normal condition. 2. When equimolar strontium was substituted for the total calcium in perfusate, the heart preparation stopped its beating, and it was not restored in spite of reperfusion with normal calcium perfusate. 3. Norepinephrine-induced positive inotropic effect was inhibited in low-calcium condition especially with low concentration of norepinephrine, but not in strontium-substitution for calcium. 4. Verapamil reduced the activity of the heart both in low-calcium and strontium-substitution as well as in normal calcium conditions. From above results, it was concluded that strontium served as a substitute of calcium in maintaining mechanical activity and in responsiveness to norepinephrine, and the influx of strontium through cell membrane is inhibited by verapamil as the influx of calcium.

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Effects of Cyclobuxine D on the Derangement Induced by Ischemia and Reperfusion in the Isolated Rat Heart (Ischemia에 의해 유발된 흰쥐의 적출 심장 손상에 대한 Cyclobuxine D의 보호효과)

  • Lee, Jong-Hwoa;Moon, Chang-Kyu;Kwon, Jun-Tack;Cho, Byung-Heon;Kim, Yu-Jae;Kim, Jong-Bae;Kim, Chang-Ho;Cha, Young-Deog;Kim, Young-Suk
    • The Korean Journal of Pharmacology
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    • v.26 no.1
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    • pp.7-12
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    • 1990
  • Cyclobuxine D is a steroidal alkaloid, which was extracted from Buxus microphylla var. koreana Nakai. In our previous studies, we clarified several pharmacological actions of cyclobuxine D: an antiinflammatory action, hypotensive and bradycardiac effects, negative inotropic effects on the several smooth muscles and cardiac muscle. The present study was undertaken to elucidate possible mechanisms by protection of myocardial tells from ischemia and reperfusion induced derangement in cardiac function and metabolism by cyclobuxine D. For this purpose, the isolated rat heart was used. Rat hearts were perfused for 60 min under ischemia conditions in the presence and absence of cyclobuxine D and verapamil, and for 30 min under reperfusion conditions. Ischemia produced a marked decline in contractile force, an increase of resting tension, an immediate release of ATP metabolites and an accumulation of calcium in the left ventricle. Cyclobuxine D (100ng/ml) ameliorated the myocardial injury produced by ischemia.

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