• The Korean Journal of Physiology and Pharmacology
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• v.3 no.6
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• pp.579-586
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• 1999

Complement-mediated neutrophil activation has been hypothesized to be an important mechanism of reperfusion injury. It has been proposed that C1 esterase inhibitor (C1 INH) may prevent the complement- dependent activation of polymorphonuclear leukocytes (PMNs) that occurs within postischemic myocardium. Therefore, The effect of C1 INH was examined in neutrophil dependent isolated perfused rat heart model of ischemia (I) (20 min) and reperfusion (R) (45 min). Administration of C1 INH (5 mg/Kg) to I/R hearts in the presence of PMNs $(100{\times}10^6)$ and homologous plasma improved coronary flow and preserved cardiac contractile function (p＜0.001) in comparison to those I/R hearts receiving only vehicle. In addition, C1 INH significantly (p＜0.001) reduced PMN accumulation in the ischemic myocardium as evidenced by an attenuation in myeloperoxidase activity. These findings demonstrate the C1 INH is a potent and effective cardioprotective agent inhibits leukocyte-endothelial interaction and preserves cardiac contractile function and coronary perfusion following myocardial ischemia and reperfusion.

• 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).

• Journal of Chest Surgery
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• v.25 no.2
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• pp.125-130
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• 1992

To evaluate the effect of oxygenation[95% O2+5% CO2] of St. Thomas Hospital No.2 cardioplegic solution[Plegisol], 20 isolated perfused rat hearts were studied under hyp-othermic[20oC] ischemic arrest for 2 hours with infusion of cardioplegic solution every 30 minutes throughout the ischemic period. Ten isolated hearts were studied with the oxygenated cardioplegic solution and 10 another isolated hearts with the nonoxygenated one. Mean oxygen tensions of the nonoxygenated and oxygenated cardioplegic solutions were 150mmHg and 470mmHg, respectively. Two in 10 hearts infused with the nonaxygenated cardioplegic solution were not recovered from nonworking heart due to persistent ventricular fibrillation. In comparing hem-odynamic parameters between both groups, the mean postischemic recovery[expressed as a percentage of its preischemic control value] was significantly greater with the oxygenated solution[in 10 recovered hearts] than the nonoxygenated solution[in 8 recovered hearts] [95.9$\pm$1.8% compared with 88.5$\pm$2.9% in peak aortic pressure, p<0.05, 75.7$\pm$5.2% compared with 43.5$\pm$6.5% in aortic flow, p<0.01, 75.5$\pm$4.6% compared with 54.1$\pm$5.6% in cardiac output, p<0.01, 78.3$\pm$4.6% compared with 60.3$\pm$4.6% compared with 60.3$\pm$6.2% in stroke volume, p<0.05, and 80.4$\pm$5.3% compared with 58.6$\pm$7.0% in dP/dT, p<0.05]. It is concluded that oxygenation of St. Thomas Hospital No.2 cardioplegic solution improves cardiac electrical stability and postischemic hemodynamic recovery after ischemic arrest in the isolated perfused rat heart.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.390-401
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• 1997

In order to investigate the pharmacological properties of New Woohwangchungsimwon Liquid (NCL), effects of Woohwangchungsimwon Liquid (CL) and NCL were compared. In isolated rat aorta, NCL and CL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) without regard to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxation of NCL and CL. NCL and CL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NCL and CL significantly decreased heart rate. NCL and CL, at high doses, had a negative inotropic effect that was a decrease of LVDP 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 excised guinea-pig papillary muscle, NCL and CL had no effects on parameters of action potential at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NCL and CL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between two preparations.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.66-78
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• 1999

In order to investigate the pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, at high doses, had a negative inotropic effect 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 excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD$_{90}$ and V$_{max}$ at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.s.

• 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.25 no.2
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• pp.131-136
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• 1992

The effect of temperature of cardioplegic solution on myocardial preservation was studied using isolated rat heart perfusion technique. Twenty Sprague-Dawley rats, weighing 120~140gm, were pretreated with intraperitoneal injection of heparin sodium[300u/kg] and then the hearts were excised after cervical herniation 30 minutes later. The hearts were perfused in isolated working heart apparatus with oxygenated modified Tyrode solution at 37oC. After 10 minutes of non working heart perfusion, the hearts were subjected to arrest for 30 minutes by administration of 5cc cardioplegic solution at the temperature of 4oC [Group I ], 15oC [Group II], 25oC [Group III], 37oC[Group IV]. At the same time, the topical cooling of heart was performed using ice saline. After arrest, the hearts were reperfused by non working heart perfusion for 1 hour with modified Tyrode solution at 37oC. The CPK, GOT and LDH in reperfusate were measured at 5,20,40,60 minutes after start of reperfusion. With the values of those, we compared the effect of temperature of cardioplegic solution on myocardial preservation. The results were as follows; 1. The enzyme values in reperfusate were highest at 5 minute and after then declined. 2. At 5 minutes after reperfusion, the enzyme values in Group I were lower than those in other Groups. These results suggest that the cardioplegic solutions using for cardiac arrest and myocardial protection can be working better at 4oC than at any other temperature.

• Journal of Chest Surgery
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• v.13 no.4
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• pp.338-345
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• 1980

We have modified an isolated perfusion rat heart model of cardiopulmonary bypass, with which we are able to screen the effects of various cardioplegic solutions and hypothermia upon the ability of the heart to survivie during and recover from period of ischemic arrest. The modified experimental model was differed from the original as follow : a heat coil chamber of atrial and aortic reservoir provided temperature control, and the perfusate was gassed with each pure oxygen and pure carbon dioxide in 95:5 ratio. The Langendorff perfusion was initiated for a 10 minute period by introducing perfusate at $37^{\circ}C.$ into the aorta from the aortic reservoir located 100 cm above the heart. The isolated perfused working rat heart model was a left heart preparation in which oxygenated perfusion medium (at $37^{\circ}C.$) entered the cannulated left atrium at a pressure of 20 cm $H_{2}O$ and was passed to the ventricle, from which it was sponeously elected(no electrical pacing) via an aortic cannula, against a hydrostatic pressure of 100cm $H_{2}O$. during this working period various indices of cardiac functin were measured. The cardiac functions were stable for over 3 hour with perfusion of Krebs-Henseleit bicarbonate buffer solution containing only glucose (11.1 mM/L). The percentage of cardiac functins were maintained about 94% on heart rate, 80.6% on peak aortic pressure, 87.7% on coronary flow and 76.3% on aortic flow rate after 3 hour of working heart perfusion at a pressure of 20 cm $H_{2}O$. We believe this preparation to be a good biochemical model for the human heart which offers many advantages including economic, speed of preparation, reproducibility, and the ability to handle large numbers.

• YAKHAK HOEJI
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• v.26 no.4
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• pp.239-251
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• 1982

The rate of deterioration of contractile force of isolated hearts from control and panax ginseng treated rats was determined and response of contractile force of the hearts from ginseng treated rats to several autonomic and other drugs was investigated. Rats weighing 150-250g were administrered orally with ginseng ethanol extract (100mg/kg) and total ginseng saponin (50mg/kg/day) for a week. Ginsenoside Rb$_{1}$ (5mg/kg/day) and ginsenoside Re (5mg/kg/day) were administered respectively for a week. The isolated hearts from rats were perfused with Krebs-Henseleit solution by using Langendorff perfusion apparatus. The control group was only able to maintain approximately 75.5% of their initial strength after 60 min of perfusion, whereas ginseng ethanol extract, total ginseng saponin treated hearts were able to sustain nearly their initial strength even after 60 min. Ginsenoside Rol treated hearts also sustained 93% of their initial strength, but there was no significant difference in the deterioration percentage of the contractile force of ginsenoside Re treated hearts. Experiments were conducted to study the response to perfusion of ginseng treated animal heart with epinephrine, isoproterenol, propranolol, and phenobarbital. The isolated hearts were perfused with Krebs-Henseleit solution containing epinephrine (10$^{-6}$ M), isoproterenol ($10^{-7}$M), propranolol ($10^{-6}$M) and phenobarbital (7{\times}10^{-3}M$) respectively. The maximum inotropic effect of epinephrine and isoproterenol was observed after 2~3 minutes of drug perfusion. Effect of epinephrine on ginseng ethanol extract and total ginseng saponin treated hearts was reduced compared with control. On the other hand, this phenomenon was not observed in ginsenoside Re treated rats but on ginsenoside $Rb_{1}$ treated rats. The positive inotropic effect of isoproterenol was reduced in the hearts from ginseng treated rats compared with control heart, Propranolol or phenobaribital decreased the contractile force in the control rats. The depressant effect of propranolol and phenobarbitat on ginseng treated rat hearts was less than those of control rat hearts. The result suggest that ginseng ethanol extract , ind total ginseng saponin and ginsenoside $Rb_{1}$ may protect the deterioration of contractile force of the heart and may attenuate the response to several drugs on hearts.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.251-270
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• 1998

The effects of Gamigunshimtang on the isolated perfused ischemic heart in rats, heart rates, left ventricular pressure, cardiac blood flow and cardiotoxicity were stu.died in H9C2 myoblast cell, myocardial slice culture The results were as follows: 1. The administration of Gamigunshimtang to the rat recovered effectively heart rate, left ventricular pressure and flow rate from the experimental ischemia in perfused rat heart. The release of lactic dehydrogenase after the ischemia also decreased compared to the control group. 2. The administration of Gamigunshimtang to H9C2 myoblast culture enhanced the cell proliferation and protected against doxorubicin and allylamine induced release of the lactic dehydrogenase into the culture medium. It also protected effectively against doxorubicin and allylamine induced decrease of Ca ATPase activity and the increase of NADPH-cytochrome C reductase activity in the microsome. 3. The administration of Gamigunshimtang to the rat myocardial slice culture protected effectively against doxorubicin and allylamine induced decreases of protein synthesis and ATP content, and increases of cvtosolic enzyme, creatin kinase into the medium and lipid peroxidation.