• The Korean Journal of Pharmacology
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• v.8 no.2
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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.

• The Korean Journal of Pharmacology
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• v.14 no.1_2
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• pp.41-46
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• 1978

The effects of sodium taurocholate(STC) and sodium deoxycholate(SDC) on cardiac function were examined by using isolated atria of rabbit and guinea pig and heart of anesthetized frog. Also the antiarrythmic action of STC and SDC on atrial arrhythmias induced by epinephrine or ouabain was studied. The results were following. The cholates exhibited a slight decrease in rate and contractile amplitude of the isolated rabbit atria. The cholates abolished partially the spontaneous arrhythmic occurring in isolated rabbit and guinea pig atria but no effect on the atrial arrhythmia induced by ouabain and epinephrine was observed. Concomitant administration of cholates with ouabain produced a marked prolongation of atrial arrhythmia in comparison to that of ouabain alone in both isolated rabbit and guinea pig atria. The cholates exhibited a marked prolongation in ventricular arrhythmia and cardiac arrest time in comparison to that of ouabain treatment. However, the combined treatment with cholates and ouabain produced a slight prolongation in comparison to that of ouabain alone in the heart of anesthetized frog. The above results suggest that cholates have a slight antiarrythmic effect on the heart but this effectiveness is different from those of propranolol that is non-selective antiarrhythmic drug.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.417-425
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• 2000

The underlying mechanism commonly applicable for both the positive and negative force-frequency relationships (FFR) was pursued in left atria (LA) of rat and rabbit. The species differences in the roles of $Na^+/Ca^{2+}$ exchanger and sarcoplasmic reticulum (SR), which are major intracellular $Ca^{2+}$ regulatory mechanisms in the heart, were examined in the amplitude accommodation to the frequency that changed from 3 Hz to the variable test frequencies for 5 minutes in the electrically field stimulated left atria (LA) of rat and rabbit. Norepinephrine strongly increased the frequency-related amplitude accommodation in both of rat and rabbit LA, while monensin, oubain or the reduced $Na^+$ and 0 mM $Ca^{2+}$ containing Tyrode solution increased the frequency-related amplitude accommodation only in the rabbit LA. Monenisn was also able to increase the frequency-related amplitude accommodation only in 1-day old rat LA but not in 4-week old rat LA that had 75% less $Na^+/Ca^{2+}$ exchanger with 97% higher SR than 1-day old rat LA. Taken together, it is concluded that the differences in the prevalence between myocardial $Na^+/Ca^{2+}$ exchanger and SR in the amplitude accommodation to the frequency-change determine the difference in the FFR between rat and rabbit heart.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.59-65
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• 1994

The experiments were performed to determine whether lidocaine interferes with the utilization of lipid as source of energy fuel for the contractile process by the isolated rat atria. Rats were starved for two days in order to inerease the lipid content of the heart. Atria from starved rats were better able to maintain their contractility in the absence of exgenous substrate, and also were more resistant to depression by lidocaine than atria from fed rats. Starvation results in a marked loss of body weight in rats. In contrast to the starved rats, the body weight of fed rats inereased with time. The smaller reduction in contractile activity of atria from the starved rats may suggest that endogenous lipid accumulates during starvation period and is used as an energy source for the contractile process in the face of a lidocaine-induced blockade in glycolysis.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.57-63
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• 1993

The abilities of metabolic substrates, glucose, pyruvate, and acetate to produce a maximal increase in the force of contraction of substrate-depleted atria from fed rats were compared to those from starved rats, in order to observe the effect of starvation on substrate utilization of the myocardium. Starvation results in a marked loss of body weight in rats. In contrast to the starved rats, the body weight of fed rats increased with time. When placed in substrate-free medium, atria from fed rats showed marked decline in contractile force. In contrast to the atria from fed rats, the substrate-depleted atria from starved rats showed much less decline of the force of contraction. In the substrate-free medium, abilities of glucose, pyruvate, and acetate to produce a maximal increase in the force of contraction of atria from fed rats were much greater than those from starved rats. The data from these studies indicate that in the substrate-free medium atria from starved rats utilize much less exogenous substrates than those from fed rats. These results suggest that starvation has no deleterious effect on contractile activity of the myocardium, and the starvation increase the storage of readily metabolizable endogenous substrstes useful for the functional activity of the isolated heart.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.930-935
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• 2005

We have investigated the effects of relatively high concentration of carbachol (CCh), an agonist of muscarinic acetylcholine receptor (mAChR), on cardiac automaticity in mouse heart. Action potentials from automatically beating right atria of mice were measured with conventional microelectrodes. When atria were treated with $100{\mu}M$ CCh, atrial beating was immediately arrested and diastolic membrane potential (DMP) was depolarized. After exposure of the atria to CCh for $\~4 min$, action potentials were regenerated. The regenerated action potentials had lower frequency and shorter duration when compared with the control. When atria were pre-exposed to pirenzepine $(1{\mu}M)$, an $M_1$ mAChR antagonist, there was complete inhibition of CCh-induced depolarization of DMP and regeneration of action potentials. Pre-exposure to AFDX-116 (11 ({2-[(diethylamino)-methyl]-1-piperidyl}acetyl)-5, 11-dihydro-6H-pyridol[2,3-b][1,4] benzodiazepine-6-one base, $1{\mu}M$), an $M_2$ mAChR antagonist, failed to block CCh-induced arrest of the beating. However, prolonged exposure to CCh elicited gradual depolarization of DMP and slight acceleration in beating rate. Our data indicate that high concentration of CCh depolarizes membrane potential and recovers right atrial automaticity via $M_1$ mAChR, providing functional evidence for the role of $M_1$ mAChR in the atrial myocytes.

• The Korean Journal of Pharmacology
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• v.11 no.2
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• pp.9-17
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• 1975

The adrenergic blocking activity and refractory period of cardiac muscle on isolated rabbit atria were measured after administration of Scutellaria. In rabbits and cats the antiarrhythmic action of Scutellaria on atrial and ventricular arrhythmias produced by epinephrine or ouabain was examined and also compared with that of propranolol and quinidine. The alcoholic extract of Scutellaria produced a marked decrease in heart rate and contractile amplitude of the isolated rabbit atria. Pretreatment with Scutellaria rendered the atria to fail to respond to epinephrine, indicating that this crude drug possesses an adrenergic blocking activity. The extract produced a marked prolongation of the refractory period of atrial muscle. The extract effectively abolished the spontaneous arrhythmia occurring in the isolated rabbit atria. As propranolol and quinidine it also suppressed the atrial arrhythmia induced by ouabain. The extract prevented, as propranolol and quinidine, the induction of ventricular arrhythmia arising from excessive dose of epinephrine in anesthetized rabbits and cats. With regard to the ventricular arrhythmia induced by a continuous infusion of ouabain, the alcoholic extract of Scutellaria exerted some suppressive effect in anesthetized rabbits but no effect on cats. From the above results, it may be concluded that Scutellaria is effective against atrial and ventricular arrhythmias. The antiarrhythmic effects of this drug may be the result of adrenergic beta receptor blocking and cardiac depressive activities including prolongation of the refractory period of cardiac muscle.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.41-48
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• 1992

A concentration of 0.01 mM bupivacaine was necessary to maintain approximately 50% depression of contractility of rat atria suspended in a modified Krebs-Ringer bicarbonate glucose medium, pH 7.4 at $30^{\circ}C$. Sodium pyruvate, sodium acetate, and fructose partially restored the contractility of the bupivacaine-depressed atria. However, 20 mM glucose had no effect on the bupivacaine-depressed atria, although this concentration of glucose markedly increased the contractility of normal atria not to be exposed to bupivacaine. Contractility of normal atria was not significantly influenced by sodium pyruvate, sodium acetate, and fructose. The results suggested that at least part of the negative inotropic action of bupivacaine is the result of inhibition of glucose uptake or utilization in the glycolytic pathway, and further pinpoint the blockade as an early step in the glycolytic sequence prior to the phosphofructokinase step.

• The Korean Journal of Pharmacology
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• v.22 no.1 s.38
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• pp.51-59
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• 1986

The effect of metabolic substrate fructose on the force of contraction of isolated rat atria depressed with lidocaine was determined. Fructose produced dose-dependent increase in the force of contraction of isolated atria depressed by substrate-free Krebs-Ringer bicarbonate medium. The maximally effective concentration of fructose was 30 mM. The isolated atria, suspended in Krebs-Ringer bicarbonate glucose medium aerated with 95% $O_2-5%CO_2$at $30^{\circ}C$ and pH 7.4, were depressed 50% by approximately 2.34 mg/100 ml of lidocaine. Addition of 30 mM fructose to these depressed atria resulted in a marked increase in the contractile force similar to that with pyruvate and acetate. Fructose had no significant effect, however, on atria exposed to low-calcium medium. The results are consistent with a previous report suggesting blockade by lidocaine of the uptake or utilization of glucose in the glycolytic pathway, and further pinpoint the blockade as an early step in the glycolytic sequence prior to the phospho-fructokinase step.

• The Korean Journal of Pharmacology
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• v.2 no.1 s.2
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• pp.21-29
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• 1966

Dichloroisoproterenol(DCI) i; one of the well known ${\beta}$-adrenergic receptor blocking agents. According to Moran and Perkins, DCI has sympathomimetic like action in relatively low concentrations. Fleming and Hawkins confirmed that DCI acts upon the receptors concerned with positive chronotropic and inotropic actions in the heart. Vogins reported that DCI, in concentration of $5{\times}10^{-8}$ to $5{\times}10^{-6}g/ml$, had properties of sympathomimetic amine causing positive inotropic and chronotropic actions in normal rat atria. And James and Nadeau found that DCI had not only adrenergic blocking effect in moderate and higher concentrations, but it also blocked the effect on the sinus node by vagal stimulation and of directly administered acetylcholine in higher concentrations. As stated above by many authors, DCI has complicated actions according to its concentrations. Our aim at the present experiments was to study the effects of DCI to the action of ouabain and acetylcholine upon the excised rabbit atria, as well as to the action of barium chloride and acetylcholine upon the excised rabbit intestine. In addition, Pan ax Ginseng is widely used as tonics in oriental nations, its pharmacological action, however, has not been clearly established. So we atempted to investigate the effects of the water extract of Panax Ginseng to the action of ouabain and DCI upon both atria and intestine. The results obtained were as follows. 1) DCI has a negative inotropic effect on the excised rabbit atria at concentration of $10^{-5}$ and a positive inotropic effect at concentration of $10^{-6}$. 2) DCI (at concentration of $10^{-6}$) potentiates the positive inotropic effect of ouabain upon the excised rabbit atria. 3) DCI antagonizes the action of acetylcholine upon the excised rabbit atria. 4) The water extract of Panax Ginseng, at concentration of $10^{-3}$, decreases the contractile force of rabbit atria, and tends to slightly increase that of rabbit atria at $10^{-4}$. 5) The water extract of Panax Ginseng exhibits a synergistic action with ouabain on the contractile force of rabbit atria. 6) DCI, in concentrations of $10^{-7}{\sim}10^{-6}$, depresses the tone and amplitude of contraction of the excised rabbit intestine. The depression of the intestinal tone markedly appears in pretreatment with reserpine 2mg/kg 24 hours. 7) DCI antagonizes the contractile effect of barium chloride on the excised rabbit atria. 8) DCI has no significant influence on the action of acetylcholine upon the excised rabbit intestine. 9) The series of those evidences indicates that DCI has a sympathomimetic-like action and more over a relaxing action directly on the excised rabbit intestine. 10) The water extract of Panax Ginseng in concentrations of $10^{-4}{\sim}10^{-3}$, has transient depression of the intestinal tone, but later gradually recovers its normal motility: 11) The water extract of Panax Ginseng has a synergistic action with ouabain on the intestinal contractility.