• 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.

• 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.

• Korean Journal of Pharmacognosy
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• v.16 no.2
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• pp.93-98
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• 1985

This investigation was performed to study the effect of Ginseng water extract on the cardiac sarcolemma $Na^+,\;K^+-ATPase$ activity of rat hearts. The Ginseng water extract (100mg/kg/day) was administered orally to Sprague-Dawley rats for one, four and seven days. The fragment of sarcolemma was prepared by the method of Matsui and Erdmann and the $Na^+,\;K^+-ATPase$ and $Mg^{++}-ATPase$ activity were measured by the method of Martins and Doty. $Na^+,\;K^+-ATPase$ activity in the rat heart treated with Ginseng water extract for 1 day was not significantly different from control value, but the activity was decreased by 13.4% in the rat heart treated for 4 days and was decreased by 20.4% in the 7 days treated group. $Mg^{++}-ATPase$ activity in the rat treated with ginseng water extract was similar to control value. It may be concluded that chronic administration of Ginseng may inhibit the $Na^+,\;K^+-ATPase$ enzyme activity, but single administration may not inhibit the activity.

• Journal of Chest Surgery
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• v.23 no.6
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• pp.1074-1083
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• 1990

This study was evaluated the metabolic, physiologic and histologic effects of myocardial protection of verapamil[isoveratril]on isolated rat hearts to 90 minutes of ischemic arrest. Heart was perfused with a modified Kreb’s Henseleit bicarbonate buffer with glucose and arrested with retrograde coronary perfusion by glucose insulin[GI], potassium and verapamil. Mean aortic systolic pressure, heart rate, coronary flows were measured and morphologic changes were examined during working heart perfusion. Perfusion and arrest were controlled four groups subjected 60 isolated rat hearts. Four groups hearts reperfused during 40 minutes after 90 minutes global ischemia for physiologic recovery. 15 hearts of four groups were assayed to histological morphologic changes. GI treated hearts recovered less than 28% of function and changed more than 80% of mitochondria of control group. Verapamil hearts[0.2, 0.1 gm/kg] recovered more than 88% of function and permitted the maintenance of continuous cellular level of Serum Glutamic Oxalaxetate Transaminase[SGOT], but declined 28% of Phosphate Kinase[CP], GI treated heart showed widespread evidence of extensive damage of mitochondria. The damage was that interstitial huge edema are present and there was contraction band formation within the swollen cells. The verapamil and potassium group were not found morphologic change compared with control group. Their functions were shown that metabolic and physiologic action of verapamil-group lasted 20 minutes longer than potassium group.

• Journal of Chest Surgery
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• v.28 no.6
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• pp.549-556
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• 1995

We investigated the effects of aprotinin, a protease inhibitor, on isolated rat heart subjected to cardioplegia and global ischemia for 4 hours and then reperfused for 40 minutes. Before ischemia, hearts were perfused with either aprotinin 1x105KIU/L[Aprotinin group,n=8 or no aprotinin[control group,n=8 added to Krebs-Henseleite solution for 30 minutes. Hemodynamic and biochemical parameters such as heart rate, LVP, dP/dt, coronary flow and creatine kinase were measured before cardioplegia and after reperfusion 10,20,30,40 minutes. After completion of experiment, wet and dry heart weight were measured for tissue water and water content evaluation. On reperfusion, recovery of LVP of aprotinin group at each time point was significantly better than that of control group[p<0.05 , and of dP/dt at reperfusion 40 minutes[p=0.034 . No statistically significant differences in heart rate, coronary flow and CK were observed between the two groups, but aprotinin group seemed to have better recovery. No significant differences in tissue water and water content were observed between the two group.These results suggest that pretreatment of aprotinin is effective in myocardial preservation in prolonged hypothermic ischemia and reperfusion.

• The Journal of Pediatrics of Korean Medicine
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• v.21 no.1
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• pp.173-187
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• 2007

Objectives : In order to verify the cardiovascular hemodynamic function of Kammaegdaejo-tang, the experiment was performed in the rats. Methods : Twelve hearts removed from male Sparague-Dawley rats weighing between 250g and 300g were perfused by the Langendorff technique with modified 37 Krebs-Henseleit's buffer solution at a constant perfusion pressure. They were randomly assigned to one of two groups, supplied with either normal saline or Kammaegdaejotang administration. Heart rate, left ventricular pressure, +dp/dt maximum, -dp/dt maximum, and -dp/dt/ +dp/dt ratio were evaluated at baseline after the administration of either normal saline or Kammaegdaejotang. Results : Kammaegdaejotang made the heart rate increasing significantly (p<0.05). Kammaegdaejotang did not effectively work on left ventricular pressure of the isolated heart(p=0.11, no significance). The significant effects of Kammaegdaejotang were observed on +dp/dt max and -dp/dt max(p<0.05). Kammaegdaejotang did not effectively work on -dp/dt/ +dp/dt ratio(p=0.24, no significance).

• Archives of Pharmacal Research
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• v.6 no.1
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• pp.69-73
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• 1983

It was reported from our laboratory that the rate of deterioration of the force of contraction was slower in heart from Panax ginseng extract treated rats. Present investigation was designed to elucidate the mechanism of the slow deterioration of contractility of ginseng treated hearts. Therefore, $^{45}Ca^{2+}$ Uptake by sarcoplasmic reticulum (SR) isolated from ginseng treated rate and control rats was studied. Rate weighing 150-250g were administered orally with ginseng ethanol extract (100mg/kg) for 10 days. Cardiac SR was isolated by differential centrifugation and $^{45}Ca^{2+}$ uptake was assessed by the Millipore method. Freshly isolated SR from treated as well as control animals did not show any differences, but after incubation for 30 and 60 min at 37.deg.C, $^{45}Ca^{2+}$ uptake of control animal SR was found to be greatly depressed. The SR of treated animal possessed a greater degree of resistance to incubation. Thus it can be concluded that ginseng may have an ability to sustain the normal function of the heart by sustaining Ca accumulation by SR involved with the excitationcontraction coupling processes.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.1
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• pp.55-62
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• 1998

${\alpha},\;{\beta}-Adrenergics$, and calcium channels were known to be related to inducing cardiac hypertrophy. Recently, it was reported that the cardiac renin-angiotensin system (RAS) was an important factor in ventricular hypertrophy. The present study was aimed to investigate the effects of ${\alpha},\;{\beta}-adrenergic$, and calcium channel blockers that might be involved in the regulation of cardiac RAS. The reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of renin gene in the perfused rat heart. Changes in angiotensin converting enzyme (ACE) activity and cyclic AMP (cAMP) content which were thought to play a role in inducing cardiac hypertrophy were measured in the perfused rat heart. The expression of renin gene was not only increased by isoproterenol with metoprolol-pretreatment but also increased by vasopressin treatment in the presence of calcium channel blocker, nifedipine or verapamil. Either prazosin alone or norepinephrine with prazosin-pretreatment significantly increased the ACE activity. However, isoproterenol with metoprolol-pretreatment significantly decreased the ACE activity. On the other hand, the ACE activity was not changed by vasopressin, nifedipine, or verapamil treatments. The content of cAMP was significantly increased by either isoproterenol or vasopressin treatment. According to these results, renin gene expression was associated with ${\beta}2$ - adrenoceptor and calcium channel. ACE activity was associated with ${\alpha}-\;and{\beta}2$ - adrenoceptor. In conclusion, ${\beta}2$ - adrenoceptor was important in cardiac renin gene expression and ACE activity and ${\alpha},\;{\beta}$ -adrenergic, and calcium channel blockers might be involved in the regulation of cardiac RAS in a complicated way.

• 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.

• Korean Journal of Veterinary Service
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• v.41 no.3
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• pp.217-220
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• 2018

A female Russian rat snake, Elaphe schrenckii, was presented for loss of movement. Physical examination showed the swelling in the area of heart. Radiographic examination revealed cardiomegaly, pericardial effusion, and a soft opacity in the area of swelling. Although pericardiocentesis to remove fluid out from the heart as well as vigorous treatments were given to the Russian rat snake, it died during treatments. Postmortem examination confirmed pericardial effusion of pale yellow, translucent fluid with mild dilation of the right atrium and ventricle. Formalin -fixed paraffin embedded tissue sections were stained with routine H&E and the classical von Kossa's method for histopathological demonstration. Histopathological examination revealed multifocal calcification in myocardium and consists of the displacement of muscular fiber by limy deposits. Congestive heart failure was suspicious for the snake when it was alive. In wild reptiles, muscle degeneration has been reported with nutrition disorders but the present case is the first report of myocardial degeneration in a Russian rat snake and contributes to the rare reports of cardiac disease in snakes.