• Journal of Chest Surgery
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• 제25권11호
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• pp.1209-1217
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• 1992

Triiodothyronine[T3] is an important regulator of the tissue metabolism, and may have potential use as an inotropic agent. The change of serum T3 level was studied in the pediatric age patients after cardiopulmonary by pass. Thyroid function was tested pre-operatively in 33 patients and total triiodothyronine[TT3] levels were serially measured during and after cardiopulmonary bypass[CPB]. After correction of dilutional effect, effects of various factors on the TT3 levels were analyzed. Abrupt fall of TT3 level was demonstrated at 15 minutes after CPB[80.1$\pm$5.9ng/dL] from the initial level of 133.6$\pm$5.3ng/dL, with some recovery at 6 hours[115.4$\pm$6.7ng/dL]. After then, gradual decrease occured reaching to the level of 77.2$\pm$4.2ng /dL at 24 hours. These falls of the TT3 after CPB were statistically significant. [p<0.01 ANOVA] Statistically significant correlation were found between the degree of hemodilution and TT3 concentration at 15 and 30 minutes after CPB[p<0.05]. But, other factors were analyzed to have no effect on TT3 levels. As the degree of the hemodilution increases, TT3 decreased less. This observation probably supports the fact that decrease of TT3 during CPB may be a result of sequestration of T3 into peripheral tissue. Although it was not statistically significant[p=0.08], the fall of TT3 was greater in the group to which plasmanate was added, than those not added. This finding seemed to be due to the increase of albumin and other thyroid-hormone-binding-proteins in the serum. Increase of these binding proteins might potentiate the sequestration of T3 into the liver and the kidney from serum, and as a consequence, decrese the serum TT3 level further.

• 생약학회지
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• 제13권4호
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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.

• 한국임상약학회지
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• 제8권2호
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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.

• Journal of Yeungnam Medical Science
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• 제5권2호
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• pp.59-69
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• 1988

Strontium은 calcium파 같은 2가 양이온으로서 평활근에서 calcium과 치환되어 평활근을 수축시킬 수 있으며, 골격근에서도 calcium과 치환되어 이를 수축시킬 수 있는 것으로 알려져 있다. 그러나 심근에서는 strontium이 calcium과 치환되어 심근을 수축시킬 수 있다는 보고가 있으나 그 기전에 대해서는 잘 알려져 있지 않다. 이에 저자는 심근에서 strontium이 calcium과 치환되어 사용될 수 있는지를 관찰하고, 그 기전을 알아보기 위해서 다음과 같은 실험을 하였다. 체중 200 g m 내지 230 g m의 흰쥐(Sprague-Dawley)의 심장을 적출하여 Langendorff씨 심관류 장치에 현수한 후 자율 수축운동을 하는 적출심장의 좌심실 내에 balloon을 넣어 수축성, 좌심실압 및 심박동수의 변화를 측정하였다. 먼저 strontium 치환용액의 관류시 나타나는 좌심실압, 수축성 및 심박동수의 변화를 관찰하였다. 그리고 심근을 흥분시키는 norepinephrine과 억제하는 verapamil이 포함된 strontium 치환용액을 관류할 때 나타나는 수축성, 좌심실압 및 심박동수의 변화를 관찰하여 다음과 같은 결과를 얻었다. 1. 저 calcium 관류용액을 관류 하였을 때 심근수축력은 현저히 억제되었으며, strontium을 첨가하여 calcium파 strontium의 농도의 합이 정상 관류용액의 calcium농도 (2.43mM)가 되게 하여 관류 하였을 때 심근 수축력은 정상 calcium농도의 관류용액을 관류했을 때의 심근 수축력에 비해 억제되지 않았다. 2. 관류용액 내의 calcium을 strontium으로 완전치환시 심정지가 유발되었으며, 이때 관류용액내에 calcium이나 strontium을 첨가 했을 때도 심근수축력은 회복되지 않았다. 3. Norepinephrine 유발 양성변력성 작용은 정상관류용액, 저calcium 관류용액 및 strontium 치환용액 모두에서 농도에 비례한 증가 양상을 보였다. Strontium 치환용액에서는 정상 관류용액에서와 차이가 없었으나, 저calcium용액에서는 고농도의 norepinephrine의 수축력 증가작용은 정상 용액에서와 차이가 없었고 저농도의 norepinephrine의 수축력 증가작용은 정상용액에서 보다 유의하게 낮았다. 4. verapamil은 calcium 용액 뿐만 아니라 strontium 치환용액에서도 심근 수축력을 현저히 감소시켰다. 이상의 실험 결과로 미루어 볼 때 strontium은 calcium과 대치되어 심근을 수축시킬 수 있으며 calcium과 같은 자격으로 norepinephrine 유발 양성 변력성작용에 참여하고 verapamil에 의해서는 calcium과 같은 양상으로 그 이동이 억제된다고 사료된다.

• 대한수의학회지
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• 제43권1호
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• pp.31-39
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• 2003

We have investigated the effect of extracellular $Mg^{2+}$ ($[Mg^2+]_o$) on action potential duration (APD) in guinea pig papillary muscles by using microelectrodes. Increasing $[Mg^2+]_o$ resulted in progressive negative inotropic effect, progressive ascending depolarization of membrane potential, and increase in intracellular $Mg^{2+}$ concentration. In addition, increase in $[Mg^2+]_o$ from 1.1 to 3, 6, 10, and 20 mM produced a reversible dose-dependent shortening of both APD at 30% ($APD_{30}$) and 90% repolarization ($APD_{90}$), especially showing a tendency towards more remarkable prominent shortening in $APD_{30}$ than $APD_{90}$. Cooling from 37 to 33 and $27^{\circ}C$ diminished the $[Mg^2+]_o$-induced APD shortening. Increase in extracellular $Ca^{2+}$ concentration from 1.8 to 3.6 and 5.4 mM caused a significant depressed effect on the increasing $[Mg^2+]_o$-induced APD shortening. Furthermore, increase in $[Mg^2+]_o$ from 1.1 to 10 and 20 mM produced a significant depressed effect on the APD shortening induced by extracellular $Ca^{2+}$. Pretreatment of verapamil and imipramine significantly attenuated the increasing $[Mg^2+]_o$-induced APD shortening in both $APD_{30}$ and $APD_{90}$, whereas the $[Mg^2+]_o$-induced APD shortening was not affected by strophanthidin, glibenclamide and tetrabutylammonium. These findings suggest that the effects of $[Mg^2+]_o$ on APD are probably due to a decrease in ionic transport across plasma membrane. In conclusion, the present study indicates that $[Mg^2+]_o$ exerts antiarrhythmic activities by antagonistic actions on intracellular $Ca^{2+}$.

• 대한약리학회지
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• 제28권1호
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• pp.41-48
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• 1992

국소마취제인 bupivacaine의 심근억제작용에 관한 기전을 규명하기 위하여, bupivacaine에 의해 수축력이 감소된 흰쥐 적출심장에 대한 각종 대사기질의 영향을 관찰한 바 다음과 같은 결과를 얻었다. 1. Krebs-Ringer glucose medium에 현수한 적출심방의 수축력은 0.01% bupivacaine에 의해 약 50% 감소되었다. 2. Pyruvate, acetate 및 fructose는 bupivacaine 억제심방의 수축력을 증가시켰으나, 정상 Krebs-Ringer medium에서의 수축력에는 현저한 영향이 없었다. 3. Glucose는 bupivacaine 억제심방의 수축력에는 별 영향이 없었으나, 정상 Krebs-Ringer medium에서의 수축력은 증가시켰다. 4. Pyruvate, acetate 및 fructose는 hypertonic medium에 의해 억제된 심방의 수축력에 영향이 없었으나, glucose는 약간의 수축력 증가를 보였다. 5. 각종 대사기질중 pyruvate가 bupivacaine 억제심방의 수축력을 최대로 증가시켰다. 이상의 결과는 bupivacaine이 심근의 glucose 섭취를 억제하거나, 해당과정을 통한 glucose의 이용을 억제하였음을 시사한다. 나아가서, bupivacaine에 의한 대사억제는 심근의 해당과정에서의 phosphofructokinase step이전의 단계에서 작용함을 시사하고 있다.

• The Korean Journal of Physiology
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• 제9권1호
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• pp.69-76
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• 1975

Cardiac performances were analyzed in intact turtle heart(Amyda japonica), perfusing with turtle Ringer-Locke's solution containing various hydrogen ion concentration, at several levels of arterial and venous pressure. 1. Ventricular work increased when venous pressure, or venous filling pressure increased, and also increased when arterial pressure increased. 2. The higher the arterial pressure, the lower the cardiac to output, for arterial pressure is the resistance to the ventricular blood flow. On the other hand, in specific arterial pressure, cardiac output was proportional to the venous filling pressure. 3. Heart rates did not change significantly during the perfusion with Ringel· solution of various pH. 4. In the heart Perfused with Ringer solution of various pH, ventricular work was the highest at PH 7.6 (at 6 $cmH_2O$ arterial pressure and 8 $cmH_2O$ venous pressure, the ventricular work was 63.09m$\cdot$cm). However, within the range of pH $7.1{\sim}7.6$, there were no significant changes in cardiac output and ventricular work. Below the level of pH 7.0, ventricular work decreased to less than 56% of maximium value (at $6cmH_2O$ arterial pressure and $8cmH_2O$ venous Pressure, ventricular work was 36.0$gm{\cdot}$ at pH 7.0). At pH 7.7 ventricular work decreased to less than 48% of maximum value (ventricular work: 30.0 $gm{\cdot}$). The nature of the cardiac performance at the various arterial and venous pressures was similar to that of normal heart. 5. Turtle heart seemed to be relatively insensitive to acid-base disturbances. The mechanism of negative inotropic effect of hydrogen ion was discussed.

• 한국임상약학회지
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• 제30권3호
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• pp.161-168
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• 2020

Background: Recently, a study comprising adult patients with sepsis admitted in the intensive care unit (ICU) was conducted. The patients were treated with high doses of intravenous ascorbic acid, thiamine, and hydrocortisone; the clinical outcomes demonstrated significant therapeutic benefits. The mortality rate in children with sepsis is approximately 25%. However, the effects of additional treatment with ascorbic acid and thiamine ("vitamin protocol") in children are rarely investigated. Methods: A retrospective analysis was performed using medical records of patients diagnosed with sepsis and admitted to the pediatric ICU (PICU) between September 2016 and June 2019. The control group received treatment only as per sepsis protocol, whereas the treated group received both sepsis protocol and the vitamin protocol. The primary endpoint was change in Vasoactive-Inotropic Score (VIS) for 5 days. The secondary endpoints included the length of stay in the PICU, duration of using mechanical ventilators and vasopressors, and mortality rate. Results: The number of patients in the treated and control groups was 33 and 24, respectively. The treated group showed greater decrease in their VIS for 5 days than the control group (44.4 vs 18.6); however, the difference was not statistically significant. The length of stay in the PICU was significantly longer for the treated group than for the control group [10.0 days (Interquartile range (IQR), 6-18) vs 4.5 days (IQR, 4-10.3); p=0.004]. Conclusions: No significant treatment benefits were observed following vitamin protocol administration to the pediatric patients with sepsis. Further studies are necessary for improving the efficacy and safety of the vitamin protocol.

• Biomolecules & Therapeutics
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• 제20권4호
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• pp.386-392
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• 2012

The endothelin (ET) signaling pathway controls many physiological processes in myocardium and often becomes upregulated in heart diseases. The aim of the present study was to investigate the effects of ET receptor upregulation on the contractile function of adult ventricular myocytes. Primary cultured adult rat ventricular myocytes were used as a model system of ET receptor overexpression in the heart. Endothelin receptor type A ($ET_A$) or type B ($ET_B$) was overexpressed by Adenoviral infection, and the twitch responses of infected ventricular myocytes were measured after ET-1 stimulation. Overexpression of $ET_A$ exaggerated positive inotropic effect (PIE) and diastolic shortening of ET-1, and induced a new twitch response including twitch broadening. On the contrary, overexpression of $ET_B$ increased PIE of ET-1, but did not affect other two twitch responses. Control myocytes expressing endogenous receptors showed a parallel increase in twitch amplitude and systolic $Ca^{2+}$ in response to ET-1. However, intracellular $Ca^{2+}$ did not change in proportion to the changes in contractility in myocytes overexpressing $ET_A$. Overexpression of $ET_A$ enhanced both systolic and diastolic contractility without parallel changes in $Ca^{2+}$. Differential regulation of this nature indicates that upregulation of $ET_A$ may contribute to diastolic myocardial dysfunction by selectively targeting myofilament proteins that regulate resting cell length, twitch duration and responsiveness to prevailing $Ca^{2+}$.

• 대한약리학회지
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• 제31권1호
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• pp.39-51
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• 1995

갑상선 기능 항진증 심장에서의 ${\beta}-adrenoceptor$의 역할은 잘 알려져 있으나 ${\alpha}-adrenoceptor$에 대해서는 알려져 있지 않은 바, 저자 등은 갑상선 기능 항진증 기니픽 심장의 유두근에서 일반 미세 전극과 이온-선택적 미세 전극을 이용하여 세포내 $Na^+$과 $H^+$ 활성도에 대한 phenylephrine의 영향을 연구하였다. Phenylephrine ($10^{-5}$ 또는 $3{\times}10^{-5}M$)에 의한 ${\alpha}_1-adrenoceptor$ 자극은 다양한 활동전위의 변동, 수축기 막전위의 과분극 ($1.5{\pm}0.1mM$), 세포내 활성도 증가 ($0.4{\pm}0.15mM$), 현저한 수축력 증가 ($220{\pm}15%$) 그리고 세포내 pH의 증가 ($0.06{\pm}0.002\;unit$)를 일으켰고, 이와 같은 변동이 prazosin과 atenolol에 의해 차단되었다. 그래서 이들 효과가 ${\alpha}_1-adrenoceptor$를 경유함을 알 수 있었고, 역시, 세포내 $Na^+$ 활성도와 수축력 증가 효과가 $Na^{+}-H^{+}$ 교환기 억제제인 ethylisopropylamiloride로 차단됨으로 보아 ${\alpha}_1-adrenoceptor$ 자극은 $Na^{+}-H^{+}$ 교환기를 자극하여 세포내 $a^{i}_{Na}$와 pH를 증가시킴을 시사한다. 이는 ${\alpha}_1-adrenoceptor$ 자극에 의한 세포내 $Na^+$감소와 초기 수축력 감소 효과를 나타내는 정상 기니픽 심장과는 매우 다른 결과로 갑상선 기능 항진증 심장에서 ${\alpha}_1-adrenoceptor$는 매우 중요한 기능을 갖고 있음을 의미한다.