• Archives of Pharmacal Research
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• v.19 no.5
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• pp.381-385
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• 1996

Rat ventricles respond with a biphasic positive inotropic effect to ouabain, low-dose and high-dose effects but rat atria with only a monophasic high dose effect. In an effect to understand the difference in response to ouabain of two tissues between rat atria and ventricles the levels of the $a_{2}$ -isoform of the $Na^{+}$, $K^{+}$-ATPase which has higher affinity for ouabain than the $a_{1}$-iso-form were determined by a $[^{3}H]$ouabain binding assay. The yield of protein per gram wet weight was about 47 mg for atria and 100 mg for ventricles. The $K_{d}$ values of ouabain for the high-affinity ouabain binding site $(a_{2} -isoform)$ were nearly the same (230 nM) in the atria and ventricles. However, the numbers of the $a_{2}$-isoform $(B_{max})$ per mg protein were approximately half in the atria. When the binding data were expressed in unit per gram tissue wet weight, the numbers of $a_{2}$ -isoform in the atria was about 25% of that in the ventricles. THese results demonstrate that the $a_{2}$ -isoform of the $Na^{+}$, $K^{+}$-ATPase in the rat atria could be detected by $[^{3}H]$ouabain binding assay and the levels of this isoform are too low to show the low-dose effect of ouabain.

• Korean Journal of Veterinary Research
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• v.35 no.2
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• pp.229-236
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• 1995

The effect of ${\alpha}_1$-adrenoceptor(${\alpha}_1$-AR) stimulation on intracellular pH($pH_i$), $Na^+$ activity($a_{Na}{^i}$) and contractility were investigated in isolated papillary muscles of euthyroid or hyperthyroid guinea pig with conventional microelectrode, $Na^+$ or $H^+$-selective microelectrodes, and tension transducer. Stimulation of the ${\alpha}_1$-AR by phenylephrine produced a decrease in $a_{Na}{^i}$ in euthyroid preparations. This decrease in $a_{Na}{^i}$ was abolished in presence of PKC activator, phorbol dibutyrate, and increased contrary to decrease. Phenylephrine also increased $a_{Na}{^i}$ in hyperthyroid ones. However, phenylrephtine produced an increase in $pH_i$ in both euthyroid and hyperthyroid ones. These changes were blocked by prazosin, an antagonist of ${\alpha}_1$-AR. These findings suggest that the changes in $a_{Na}{^i}$ and $pH_i$ are mediated by a stimulation of $Na^+-H^+$ exchange via ${\alpha}_1$-AR stimulation. This study focused on the increase in $a_{Na}{^i}$, $pH_i$ and contractility. The increase in $pH_i$ was blocked by amiloride or EIPA, $Na^+-H^+$ exchange inhibitors. Therefore, the increase in $a_{Na}{^i}$ and $pH_i$ mediated by ${\alpha}_1$-AR appeared to be due to an influx of $Na^+$ and a reduction of $H^+$ through $Na^+-H^+$ exchange. This study also revealed that the increase in $pH_i$ and $a_{Na}{^i}$ might be related to the sustained positive inotropic response. The $a_{Na}{^i}$ increase may contribute to the intracellular $Ca^{2+}$ through the $Na^+-Ca^{2+}$ exchange, and the $pH_i$ increase could cause an increase in the $Ca^{2+}$ sensitivity of myofilaments and may augment the ${\alpha}_1$-AR-mediated positive inotropic response.

• The Korean Journal of Pharmacology
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• v.10 no.2
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• pp.31-37
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• 1974

Citrus unshiu Marc., a family of Rutaceae, has been used as antitussives, antiemetics, expectorants, spasmolytics, stomachics and digestants in oriental medicine. But there is few reports on the pharmacological effects of Citrus unshiu pericarpium. Present experiment was performed to observe the effects of the water extract of Citrus unshiu on isolated auricle and intestine in rabbits and blood pressure in rats and also to study on the active component on the cardiovascular system by means of thin layer chlomatography and spectrophotometer. 1. The water extract showed positive inotropic and positive chronotropic effect in the concentration of $1{\times}10^{-4}g/ml$, $5{\times}10^{-4}g/ml$, and $1{\times}10^{-3}g/ml$. 2. The motility of isolated rabbit intestine was significantly depressed by the water extract. 3. The blood pressure was markedly increased by the water extract. 4. The blood vessel of rabbit ear was constricted by perfusion of the ether extract. 5. The purified alkaloid of Citri pericarpium by ion exchange resin showed the same Rf value with l-synephrine on thin layer chromatography. 6. The purified alkaloid of Citri pericarpium by thin layer chromatography showed the same absorption curve with l-synephrine in the ultraviolet scanning.

• Journal of Chest Surgery
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• v.22 no.4
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• pp.609-619
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• 1989

During aortic valve surgery, cardioplegic solution is delivered through direct cannulation of both coronary ostia. Since this approach may cause an intimal injury leading to acute dissection or late ostial stenosis, this study was undertaken to evaluate myocardial protective effect of retrograde perfusion of cardioplegia [RCSP <% RRAP] in 18 clinical cases, which were compared with antegrade perfusion of cardioplegia in 27 clinical cases. This study were investigated 1] cease and return of electromechanical activity after cardioplegia infusion 2] the myocardial temperature during operation 3] the aortic cross clamping time and total bypass time 4] frequency of DC shock for defibrillation 5] need for inotropic drugs after operation 6] electrocardiographic evidence of myocardial infarction or ventricular arrhythmia after operation 7] the enzymes activity during preoperative and postoperative period as an evaluation of myocardial ischemic injury and 8] operative mortality rate The combination of retrograde cardioplegia and topical cooling with ice slush yielded promptly hypothermia of myocardium and shorter aortic cross-clamping time compared with antegrade cardioplegia [P < 0.05]. The temperature of the interventricular septum was maintained below 20oC by continuous perfusion or intermittent perfusion of cold blood cardioplegia and other results were no statistically significant difference between the two methods [P >0.05]. This technique provides clear operative field and avoids some serious complications which are caused by coronary ostial cannulation. These results suggested that the retrograde perfusion of cardioplegia is a simple, safe, and effective means of myocardial protection during open heart surgery.

• Tuberculosis and Respiratory Diseases
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• v.76 no.3
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• pp.127-130
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• 2014

The risk of dying from a pulmonary embolism (PE) is estimated to be about 30% if inotropic support is required and no cardiopulmonary arrest occurs. Fibrinolysis in massive PE is regarded as a life-saving intervention, unless there is a high risk of bleeding following the use of the fibrinolytic therapy. Rivaroxaban is an oral factor Xa inhibitor, however its anticoagulation effects before or after administration of fibrinolytics in massive PE are still unknown. Two patents were admitted: 61-year-old woman with repeated syncope, and a 73-year-old woman was admitted with dyspnea and poor oral intake. Systemic arterial hypotension with radiologic confirmation led to a diagnosis of massive PE in both patients. Rivaroxaban was administered before in one, and after firbrinolytic therapy in the other. One showed similar efficacy of rivaroxaban with currently used anticoagulants after successful fibrinolysis, and the other one without antecedent administration of the fibrinolytic agent showed unfavorable efficacy of rivaroxaban.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.301-301
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• 1994

〔$^3$H〕Ouabain binding parameters(K$\_$D/ and B$\_$max/,) in homogenates prepared fpom control rat ventricular strip and Langendorff preparations which were not previously exposed to ouabain were compared to those in homogenates from ventricular strip and Langendorff preparations that had been first exposed to a complete ouabain dose-response curve(10$\^$-7/M to 10$\^$-4/ M). In rat ventricular strips and Langendorff perfused rat heart preparations, cumulative dose-response cruves of ouabain revealed biphasic positive inotropic effects, a "low-dose" and a "high-dose" effect with ED$\_$50/ values of 0.5${\mu}$M and 35${\mu}$M ouabain, respectively- The "low-dose" effect in rat ventricular strips disappeared or was diminished significantly when the ouabain dose-response curve wag repeated after the washout of the effects of the first curve, whereas the maximal "high-dose" effect was identical in both exposures to oubain. However, there was no change in the "low-dose" effects in both sets of the Langendorff perfused hearts. The contractile activity of the pre-exposed strips did not indicate the presence of residual ouabain since their basal contractile force was decreased 10% compared to initial control. 〔$^3$H〕Ouabain binding parameters, K$\_$D/ and B$\_$max/, were not changed comparing homogenate of control ventricular strips with that of strips pre-exposed to ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site(${\alpha}$$_2$ isoform).

• Journal of Veterinary Clinics
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• v.29 no.3
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• pp.203-206
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• 2012

Treatment for heart failure is directed to reduce atrial volume overload by diuretic agents, to lessen ventricular pressure overload by vasodilatory agents and to increase myocardial performance through inotropic agents. Of those cardiac therapeutics, diuretic agents are the most important to control heart failure in dogs, although long-term use often causes detrimental side-effects such as acute renal failure and electrolyte abnormalities. Thus, this study was designed to find a new diuretic agent from medicinal herbs which has better diuretic effect and less unfavorable complications in dogs. In a preliminary study performed with 5 normal healthy dogs, the extract from Akebia quinata Decaisne showed mild to moderate diuretic effect (0.3-0.5 potency of furosemide 2 mg/kg) and minimal changes in serum chemistry and electrolyte. Although the study population was not large enough and study period was not sufficient enough, this study found a good alternative diuretic agent which can replace or reduce the use of furosemide in dogs with heart failure.

• Archives of Pharmacal Research
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• v.29 no.11
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• pp.990-997
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• 2006

Sarcococca saligna is a shrub that is traditionally used for its medicinal properties in Pakistan. In this study we report the cardio-suppressant, vasodilator and tracheal relaxant activities of the aqueous-methanolic extract (Ss.Cr) of the plant. Ss.Cr, that tested positive for the presence of saponins, flavonoids, tannins, phenols, and alkaloids, exhibited a dose-dependent (0.3-5 mg/mL) negative inotropic and chronotropic effect on the isolated guinea-pig atrium which was resistant to atropine ($1\;{\mu}M$) and aminophylline ($10\;{\mu}M$) pretreatment. In rabbit thoracic aorta, Ss.Cr dose-dependently (0.1-3 mg/mL) relaxed the high $K^{+}$ (80 mM) and phenylephrine ($PE,\;1\;{\mu}M$)-induced contractions, indicating a possible $Ca^{++}$ channel blocking (CCB) effect. When tested against PE ($1\;{\mu}M$) control peaks in normal $Ca^{++}\;and\;Ca^{++}$-free Kreb's solution, Ss.Cr exhibited dose-dependent (0.1-3 mg/mL) inhibition, being more potent in relaxing the PE responses in $Ca^{++}$-free Kreb's solution, thus indicating specific blockade of $Ca^{++}$ release from the intracellular stores. Ss.Cr also relaxed the agonist-induced contractions in: a) rat aorta irrespective of the presence of endothelium or nitric oxide synthase inhibitor L-NAME and b) rabbit and guinea-pig tracheal strips. The data shows that Ss.Cr possesses possible $Ca^{++}$ channel blocking activity which might be responsible for its observed cardio-suppressant, vasodilator and tracheal relaxant effects though more tests are required to confirm this $Ca^{++}$ channel blocking effect.

• Journal of Yeungnam Medical Science
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• v.8 no.2
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• pp.52-62
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• 1991

The toxic effect of azalea extract, expecially on cardiovascular system, is relatively unclear. The purpose of this study is to study the possible underlying mechanism and effect of toxic ingredient of azalea on cardiovascular system. The 71 healthy rabbits were divided into 10 groups : In group as preliminary study ; 4cc of normal saline was administered intravenously(N) ; 0.7gm/kg and 1.0gm/kg of azalea extract was administered respectively in the same route, volume(A1, A2) ; atropine was administered intravenously(A) ; after pretreatment with atropine(0.04mg/kg) to block parasympathetic system, azalea extract was injected like the above groups(AA1, AA2) ; normal saline, 0.7gm/kg and 1.0gm/kg of azalea extract were administered respectively with 0.2cc(1 : 1000) epinephrine(E0,E1,E2). We measured the following indices at I minute interval during first 10 minutes and then 10 minute interval during next 30 minutes : RR interval, QTc interval, maximal systolic and diastolic pressure drop with occuring time and presence of significant arrhythmia. The results were as follows : 1. The changes of RR interval, QTc interval were significantly increased in groups by Azalea extract. The blood pressure change was significantly decreased in groups by Azalea extract. There were no significant differences according to dosage of Azalea extract. 2. The changes of RR interval, blood pressure were significant differences between administration of atropine and Azalea extract after pretreatment with atropine, but not in the change of QTc interval. 3. There were no significant differences in the change of RR interval, ATc interval, blood pressure drop according to pretreatment with atropine. 4. The interaction between epineprine and Azalea extract was not noted by the effect of epineprine itself. 5. The ST change by 0.7gm/kg, 1.0gm/kg of Azalea extract was revealed in 1 case(14.0%), 7 case(100%), respectively. 6. Most of all cases with arrhthymia, ventricular tachycardia, ventricular fibrillation, were noted in the group by epineprine, except one case by Azalea extract(1.0gm/kg). It was idioventricular rhythm. In conclusion, azalea extract has negative inotropic and chronotropic effect with arrhythmogenic potential possibly through direct myocardial ischemia or injury but we cann't be absolutely exclusive of actions of autonmic nervous system, especially parasympathetic nervous system.

• The Korean Journal of Pharmacology
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• v.10 no.2
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• pp.43-54
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• 1974

The cactus family Cactaceae, numbering about 1,500 species, is a fleshy-stemmed perennial plant which is principally distributed in the south and north America. On the other hand, the cactus plant is presumed to be introduced into Korea in 1912-1945, thereafter it has been cultivated merely in favor of ornamentation with the exception of being occasionally used as medication among laymen. Opuntia elata which belongs to Opuntia genus, the Cactaceae family is one of the cacti being cultivated a great deal in Korea. Cho et. al. reported in 1974 that Opuntia dilenii manifested the cardiac inhibitory effect and oxytocic effect, and its mechanism might be partially due to the direct action. Besides this, there are few reports on the pharmacological research concerning Opuntia genus to be demonstrated in Korea. However, some other cacti have the remarkable pharmacological effects; the active ingredients, mescaline, anhalamine, anhalanine, etc. from Peyote cactus (Lophophora williamsii) belonging to Lophophora genus have the psychotomimetic and sympathomimetic effects, and the cardioactive glycosides from Cactus Grandifolius (Selenicereus grandiflorus) belonging to Cereus genus have the cardioactive and diuretic effects. The authors hereby inquired into this study to find out the propriety of the pharmacological properties of the ethanol extract of Opuntia elata (EX) on the heart, blood pressure, respiration, intestine and uterus in the experimental animals. The results of the experiment were as follows: 1. Administration of EX manifested the cardiac inhibitory effect caused by the negative inotropic action in the isolated heart of frog, and the pretreatment of atropine did not affect the inhibitory effect produced by EX. 2. Administration of EX manifested the transient hypotensive effect in the intact rabbit, and the pretreatment of atropine did not affect the hypotensive effect produced by EX. 3. Administration of the small dose of EX manifested no significant effect, but moderate dose or more the stimulating effect, and the large dose the asphyxia on the respiratory motility in the intact rabbit. 4. Administration of EX manifested the sustained augmentation of contractility in the excised duodenum of rabbit, and the pretreatment of atropine did not affect the stimulating effect produced by EX. 5. Administration of EX manifested the sustained augmentation of contractility in the excised pregnant uterus of rabbit, and the pretreatment of atropine and oxytocin did not affect the oxytocic effect produced by EX, but that of barium chloride more or less stimulated the oxytocic effect produced by EX.