• 대한수의학회지
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• 제39권3호
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• pp.463-471
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• 1999

Magnesium($Mg^{2+}$) is one of the most abundant intracellular divalent cation. Although recent studies demonstrate that adrenergic receptor stimulation evokes marked changes in $Mg^{2+}$ homeostasis, the regulation of $Mg^{2+}$ by dopaminergic receptor stimulation is not yet known. In this work, we used dopaminergic agents to identify which type(s) of receptors were involved in the mobilization of $Mg^{2+}$ by dopaminergic receptor stimulation in the perfused rat hearts, isolated myocytes and circulating blood. The $Mg^{2+}$ content was measured by atomic absorbance spectrophotometry. Dopamine(DA), apomorphine(APO) and pergolide stimulated $Mg^{2+}$ efflux in the perfused rat hearts and these effects were inhibited by haloperidol or fluphenazine, nonselective dopaminergic antagonists. SKF38393, a selective doparminergic agonist, increased $Mg^{2+}$ efflux from the perfused hearts in dose dependant manners and SKF38393-induced $Mg^{2+}$ efflux was blocked by haloperidol. However, dopaminergic agonists-induced $Mg^{2+}$ efflux was potentiated in the presence of sulpiride or eticlopride, $D_2$-selective antagonist, from the perfused hearts. This increase of $Mg^{2+}$ efflux was blocked by haloperidol or imipramine. DA or pergolide increased in circulating $Mg^{2+}$ from blood. By contrast, PPHT stimulated $Mg^{2+}$ influx(a decrease in efflux) from the perfused hearts and circulating blood. PPHT-induced $Mg^{2+}$ influx was blocked by fluphenazine in the perfused hearts. DA-stimulated $Mg^{2+}$ efflux was inhibited by dopaminergic antagoinst in the isolated myocytes. In conclusion, the flux of $Mg^{2+}$ is modulated by DA receptor activation in the rat hearts. The efflux of $Mg^{2+}$ can be increased by $D_1$-receptor stimulation and decreased by $D_2$-receptor stimulation, respectively.

• 약학회지
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• 제26권4호
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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.

• Biomolecules & Therapeutics
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• 제7권4호
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• pp.354-361
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• 1999

In this study, the effects of tauroursodeoxycholic acid (TUDCA) on ischemia/ reperfusion injury were investigated on isolated heart perfusion models. Hezrts were perfused with oxygenated Krebs-henseleit solution (pH 7.4, $37^{\cire}C$) on a Langendorff apparatus. After equilibration, isolated hearts were treated with TUDCA 100 and 200 $\mu\textrm{M}$ or vehicle (0.02% DMSO) for 10 min before the onset of ischemia in single treatment group. In 7 day pretreatment group. TUDCA 50, 100 and 200 mg/kg body weight were given orally for 7 days before operation. After global ischemia (30 min), ischemic hearts were reperfused for 30 min. The physiological (i.e. heart rate, left ventricdular developed pressure, coronary flow, double product, time to contracture formation) and biochemical (lactate dehydrogenase; LDH) parameters were evaluated. In vehicle-treated group, time to contracture formation was 810 sec during ischemia, LVDP was 34.0 mmHg at the endpoint of reperfusion and LDH activity in total reperfusion effluent was 34.3 U/L. Single treatment with TUDCA did not change the postischemic recovery of cardiac function, LDH and time to contractur compared with ischemic control group. TUDCA pretreatment showed the tendency to decrease LDH release and to increase time to contracture and coronary flow. Our findings suggest that TUDCA does not ameliorate ischemia/reperfusion-reduced myocardial damage.

• Archives of Pharmacal Research
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• 제22권5호
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• pp.479-484
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• 1999

In this study, the effects of ursodeoxycholic acid (UDCA) on ischemia/reperfusion injury were investigated on isolated heart perfusion model. Hearts were perfused with oxygenated Krebs-Henseleit solution (pH 7.4, $37^{\circ}C$) on a Langendroff apparatus. After equilibration, isolated hearts were treated with UDCA 20 to 160 $\mu$M or vehicle (0.04% DMSO) for 10 min before the onset of ischemia. After global ischemia (30 min), ischemic hearts were reperfused and allowed to recover for 30 min. The physiological (i.e. heart rate, left ventricular developed pressure, coronary flow, double product and time to contracture formation) and biochemical (lactate dehydrogenase; LDH) parameters were evaluated. In vehicle-treated group, time to contracture formation was 21.4 min during ischemia, LVDP was 18.5 mmHg at the endpoint or reperfusion and LDH activity in total reperfusion effluent was 54.0 U/L. Cardioprotective effects of UDCA against ischemia/reperfusion consisted of a reduced TTC $(EC_{25}=97.3{\mu}M)$, reduced LDH release and enhanced recovery of cardiac contractile function during reperfusion. Especially, the treatments of UDCA 80 and $160 {\mu}M $ significantly increased LVDP and reduced LDH release. Our findings suggest that UDCA ameliorates ischemia/reperfusion-induced myocardial damage.

• 대한한의학회지
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• 제18권2호
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• pp.340-354
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• 1997

Background : The stenosis of the coronary artery results in a decrease in the myocardial oxygen supply, ischemia and infarction. Jakamchotang as a drug of liquid is generally regarded to have the effect of arrythmia, palpitation from Heart disease and promoting the flow of Ki and Blood. Methods : The purpose of this experimental study is to find whether Jakamchotang is effective or not in curing ischemia in isolated perfused rat hearts and to measure the degree of its curing effect. In this study, under the Langendorff apparatus, ischemia was induced in isolated Sprague-Dawley rat hearts by ceasing the perfusion for 20 minites. Subjects were divided into a normal saline orally administered group(control group), an Jakamchotang orally 100mg administered group (sample A), an Jakamchotang orally 300mg administered group (sample B), and an Jakamchotang injection perfused group(sample C). The heart rates, left ventricular pressure, myocardial dilatation/contraction, cardiac perfusion flow and cardiac ezyme(LDH, CPK) of the four group were measured and compared in order to assess the influence of Jakamchotang on isolated perfused rat hearts recovering abillity from ischemia and infarction. results : 1. Heart rates were increased significantly in Jakamchotang orally 100mg administered group, Jakamchotang orally 300mg administered group and Jakamchotang injection perfused group on perfusion and reperfusion(p<0.01). 2. Left ventricular pressure were increased significantly in Jakamchotang orally 100mg administered group and 300mg administered and Jakamchotang injection perfused group(p<0.01) in comparison with control group on perfusion, but every group did not significant on reperfusion. 3. While there were no differances in each group's abillities of myocardial dilatation, the ability of myocardial constriction of Jakamchotang 100mg administered group only on perfusion was significantly greater than that of control group(p<0.05). 4. CBF was no significant on perfusion and reperfusion in comparison with control group(N.S.) 5. LDH was not significantly decreased on perfusion, but significactly decreased in Jakamchotang orally 100mg administered group, Jakamchotang orally 300mg administered group on reperfusion. 6. CPK was significantly decreased in Jakamchotang orally 100mg administered group, 300mg administered and Jakamchotang injection perfused group on perfusion(p<0.01), but was not significantly in Jakamchotang 300mg administered group only on reperfusion(P<0.05) Conclusion : According to the result above, Jakamchotang have an effect to recover in the isolated perfused rat hearts. Especially, the effect of Jakamchotang in orally adminstered group is greater than that of Jakamchotang injection perfused group on preischemia. The followings are the two important results of this study: First, the effect of Jakamchotang used traditionally on heart disease was proved statistcally under the Langendorff apparatus. Second, on the basis of this study, the effect of other type medications on myocardial ischemia can be evaluted in further studies.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제1회 추계심포지움 and 제2회 생리분자과학연구센터워크숍
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• pp.25-27
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• 1993

The effect of alpha$_1$-adrenergic stimulation on cardiac automaticity changes during myocardial development. To illustrate, in isolated tissues from the mature canine heart, alpha$_1$-adrenergic stimulation usually induces a decrease in automatic rate. On the other hand, many early neonatal fibers exhibit an increase in automatic rate In response to alpha$_1$-agonists, which is not seen in the adult.

• 대한한의학회지
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• 제19권1호
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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.

• 대한약리학회지
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• 제8권2호
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• pp.63-69
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• 1972

The effects of omission of buffers from Krebs-Ringer medium on contractile activity, membrane potentials and ATP content of electrically stimulated isolated rat atria were investigated. 1) Contractile status: A rapid and marked depression of the contractile activity of atria occurred when buffer-free medium was substituted for the normal Krebs-Ringer medium. 2) Electrical status: The omission of buffers from medium did not alter the resting or action potential magnitudes of atria. However, the action potential duration was on initial increase followed by a decrease in the buffer-free medium. 3) ATP concentration: The omission of buffers from medium resulted in a marked decrease in the ATP levels of atria. It has been also found in the present study that bicarbonate buffer plays an important role for the maintenance of the contractility and ATP levels of the heart. The contractile depression by the omission of buffers was not directly associated with electrical alterations in resting or action potentials of the heart. In the absence of bicarbonate-buffer, glucose no longer plays to maintain the contractile activity and the ATP levels of rat atria.

• 약학회지
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• 제27권2호
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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.

• 대한한방소아과학회지
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• 제24권3호
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• pp.106-120
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• 2010

Objectives: Sanjointang has been clinically used much for treating sleeplessness. However, the effects of Sanjointang in artificial sleep deprivation situations are not known. The purpose of this study is to evaluate the heart rate, left ventricular systolic pressure, left ventricular diastolic pressure, +dp/dt maximum, -dp/dt maximum, and -dp/dt / +dp/dt ratio which are related to the hemodynamic functions of the heart by using sleep-deprived Sparague-Dawley rats, in order to clarify the impact of Sanjointang on hemodynamic functions of the heart of sleep deprived rats. Methods: Eighteen hearts were removed from the male Sparague-Dawley rats weighting about 180g were perfused by the Langendorff technique with modified 37 Krebs-Henseleit's buffer solution at a constant perfusion pressure (60mmHg). They were randomly assigned to one of the following three groups, 1) Normal group (those which did not have sleep deprivation and received normal saline administration), 2) Control group (sleep deprived and normal saline administered), 3) Sample group (sleep deprived and Sanjointang was administered). Control and sample groups rats were deprived 96 hours of sleep by using the modified multiple platform technique. Heart rate, left ventricular systolic pressure, left ventricular diastolic pressure, +dp/dt maximum, -dp/dt maximum, -dp/dt / +dp/dt ratio were evaluated at baseline after the administration of either normal saline or Sanjointang. Results: The heart rate and -dp/dt / +dp/dt ratio was significantly decreased in rats with 96 hours of sleep deprived significantly decreased. The change in the heart rate after administering Sanjointang did not show any significant difference. The left ventricular systolic pressure of the removed heart significantly decreased due to Sanjointang administration, while the left ventricular diastolic pressure significantly increased (p<0.05). The +dp/dt maximum and -dp/dt maximum both significantly decreased in the removed heart after administering Sanjointang. (p<0.05). There was no significant difference observed in the -dp/dt / +dp/dt ratio after administering Sanjointang. Conclusions: According to the results above, sleep deprivation significantly decreases heart rate and -dp/dt / +dp/dt ratio. This is considered as a result of exhaustion due to accumulation of fatigue. Meanwhile, Sanjointang reduced left ventricular systolic pressure and raised left ventricular diastolic pressure, and relieved the contractility and relaxation of the myocardium. Consequently, this reduces the burden of the heart and creates a relatively stabilized heart condition similar to a sleeping condition.