• 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.

• Journal of Chest Surgery
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• v.18 no.2
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• pp.205-213
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• 1985

It is well documented that calcium is essential to cardiac contraction and the amplitude of contractility is proportional to the ionized calcium not to total calcium. Changes of serum ionic calcium before and after extracorporeal circulation were observed in fifty two patients operated on at Dept. of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, from May 21st, 1984, to July 6th, 1984. They were 28 males and 24 females including 21 acyanotic congenital heart diseases, 21 cyanotic congenital heart diseases, and 10 acquired valvular heart diseases. In general, preoperative serum ionic calcium was around the normal level, but those of immediate postoperative day and postop-first day were decreased subnormally with significance [P<0.05 vs. preop.]. From postop-third day, serum ionic calcium was returned to normal range. No significant difference was noticed in subgroups divided by 10 Kg of body weight and by the methods of myocardial protection. But the change of serum ionic calcium in the patients with prolonged pump time over 90 minutes was remarkable and the values were as follow; on immediate postop-day 1.780.18 mEq/L vs. 1.970.20 mEq/L [P<0.005],on postop-first day, 1.940.20mEq/L vs. 2.060.12 mEq/L [P<0.025], on postop-third day, 2.030.11mEq/L vs. 2.150.13mEq/L [P<0.01], and on postop-seventh day, 2.030.09mEq/L vs. 2.190.11mEq/L [P<0.005]. In summary, the serum ionic calcium was lowered after extracorporeal circulation and even severer degree according to the prolongation of bypass time. So, after extracorporeal circulation esp. in the cases with prolonged bypass time, early correction of lowered serum ionic calcium would be helpful to the postoperative hemodynamics.

• The Korean Journal of Pharmacology
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• v.19 no.1
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• pp.61-69
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• 1983

Hypothermia is an essential preparatory procedure for cardiac surgery, which lows the metabolic rate and myocardial oxygen demand. However, hypothermia itself is a stress enough to change the tonus of sympathoadrenal system, especially the cardiovascular responses to the catecholamines. It is reported that the positive chronotropic and inotropic response of catecholamines is exaggerated during hypothermia because of decreased norepinephrine uptake at the junctional cleft or decreased catecholamine metabolism. On the other hand, there are evidences of diminished catecholamines responses in low temperature ana further, interconversion of adrenergic receptors is also suggested. Present investigation was planned to observe the cardiovascular changes and its responses to catecholamines during surface hypothermia in cat. Healthy mongrel cats, weighing $2{\sim}3\;kg$, anesthetized with secobarbital(30 mg/kg), were permitted to hypothermia by external cooling technic. Esophageal temperature, ECG (lead II), heart rate, left ventricular pressure with dP/dt, carotid artery pressure and left ventricular contractile force were monitored with Polygragh (Model 7, Grass), and the respiration was maintained with artificial respirator (V 5 KG, Narco). Followings are summarized results. 1) Surface cooling caused progressive decrease of body temperature and reached $l8.8{\pm}0.8^{\circ}C$ and $16.9{\pm}0.6^{\circ}C$ in 120 and 150 min respectively, after immersion into ice water, and ventricular fibrillation was developed at $20.4{\pm}0.65^{\circ}C$. 2) Heart rate, blood pressure and myocardial contractility were decreased after initial increase as the body temperature falls. 3) Systolic and diastolicdd P/dt of left ventricular pressure were decreased and that the decrement of diastolic dP/dt was more marked. 4) On ECG, ST depression, Twave inversion and prolongation of PR interval were prominent in hypothermia, and moreover, the prolongation of PR interval was marked just prior to the development of ventricular fibrillation. 5) The cardiovascular responses to catecholamines, especially to isoproterenol, were suppressed under hypothermia.

• Toxicological Research
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• v.16 no.3
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• pp.211-219
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• 2000

The therapeutic effect of AS2-006A, a derivative of asiaticoside, has been studied and is being developed as a new wound-healing agent. In the present study, the general pharmacological effects on 1) central nervous system, 2) autonomic nervous system, 3) respiratory system, 4) gastrointestinal system. 5) cardiovascular system. and 6) urinary system were assessed in experimental animals and in in vitro models. 1. In vivo animal study: External applications of the 1 % gel ointment of AS2-006A to rats at the doses of 200. 600 or 2000 mg/kg body weight showed no observable pharmacological effects. The effects on the central nervous system were assessed by observation of behavior, hexobarbital-induced sleeping time, pentetrazole-induced convulsion assay, body temperature measurements, and observations on spontaneous activity and catalepsy. The gel ointment exhibited no effects on the cardiovascular system (i.e. blood pressure and heart rate), renal physiology (i.e. urine volume and electrolytes excretion) and gas-trointestinal physiology (i.e. intestinal charcoal propulsion and gastric mucosal irritation). 2. In vitro experiments: The effects of AS2-006A on the physiology of smooth and cardiac muscles were assessed. Muscle contractions were isotonically and isometrically measured in organ chambers using a physiograph. Cumulative additions of AS2-006A (10$^{-9}$ -10$^{-5}$ M) induced no changes in the tension of isolated guinea pig ileum and tracheal muscles. AS2-006A only slightly increased contractility of rat atrial and papillary muscles at 10$^{-2}$ M, which was not statistically different from control. These data showed that the gel ointment of AS2-006A could be externally applied as a wound-healing agent with no potential side effects.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.2
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• pp.223-230
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• 1999

Alterations of cardiovascular function associated with various thyroid states have been studied. In hyperthyroidism left ventricular contractility and relaxation velocity were increased, whereas these parameters were decreased in hypothyroidism. The mechanisms for these changes have been suggested to include alterations in the expression and/or activity levels of various proteins; ${\alpha}-myosin$ heavy chain, ${\beta}-myosin$ heavy chain, ${\beta}-receptors,$ the guanine nucleotide-binding regulatory protein, and the sarcolemmal $Ca^{2+}-ATPase.$ All these cellular alterations may be associated with changes in the intracellular $Ca^{2+}$ concentration. The most important regulator of intracellular $Ca^{2+}$ concentration is the sarcoplasmic reticulum (SR), which serves as a $Ca^{2+}$ sink during relaxation and as a $Ca^{2+}$ source during contraction. The $Ca^{2+}-ATPase$ and phospholamban are the most important proteins in the SR membrane for muscle relaxation. The dephosphorylated phospholamban inhibits the SR $Ca^{2+}-ATPase$ through a direct interaction, and phosphorylation of phospholamban relieves the inhibition. In the present study, quantitative changes of $Ca^{2+}-ATPase$ and phospholamban expression and the functional consequences of these changes in various thyroid states were investigated. The effects of thyroid hormones on (1) SR $Ca^{2+}$ uptake, (2) phosphorylation levels of phospholamban, (3) SR $Ca^{2+}-ATPase$ and phospholamban protein levels, (4) phospholamban mRNA levels were examined. Our findings indicate that hyperthyroidism is associated with increases in $Ca^{2+}-ATPase$ and decreases in phospholamban levels whereas opposite changes in these proteins occur in hypothyroidism.

• Korean Journal of Veterinary Research
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• v.37 no.1
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• pp.103-110
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• 1997

The experiments were carried out to elucidate the relationships between neurogenic effects of electrical transmural nerve stimulation and effect of adenosine 5'-triphosphate(ATP) to purinoceptor on the urinary bladder smooth muscle of pig. The results were as follows : 1. The contractile responses induced by electrical transmural nerve stimulation(10V or 20V, 0.5msec, 10sec) were the frequency(2~64Hz) dependent manner. 2. The contractile response induced by carbachol was responsed with a dose-dependent manner and the maximum contractility was $10^{-4}M$. 3. The contractile responses induced by ATP were increased in a dose-dependent manner ($10^{-5}{\sim}10^{-3}M$). 4. The contractile response induced by electrical transmural nerve stimulation(10V, 2~32Hz, 0.5msec, 10sec) was partially blocked by the treatment with atropine($10^{-5}M$), and was powerfully inhibited by 3 times of addition with ATP($10^{-5}M$). 5. The contractile response induced by electrical transmural nerve stimulation(10V, 2~32Hz, 0.5msec, 10sec) was partially blocked by the treatment with atropine($10^{-5}M$), and was completely blocked by the desensitization of the $P_{2X}$-purinoceptor using ${\alpha}$, ${\beta}$-methylene ATP($5{\times}10^{-5}M$). These results suggest that purinergic nerve was innervated, and ATP and acetylcholine was released by the electrical transmural nerve stimulation in urinary bladder smooth muscle of pig.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.329-337
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• 1999

Thyroid hormone-induced cellular dysfunctions may be associated with changes in the intracellular $Ca^{2+}$ concentration. The ryanodine receptor, a $Ca^{2+}$ release channel of the SR, is responsible for the rapid release of $Ca^{2+}$ that activates cardiac muscle contraction. In the excitation-contaction coupling cascade, activation of ryanodine receptors is initiated by the activity of sarcolemmal $Ca^{2+}$ channels, the dihydropyridine receptors. In hyperthyroidism left ventricular contractility and relaxation velocity were increased, whereas these parameters were decreased in hypothyroidism. The mechanisms for these changes have been suggested to include alterations in the expression and/or activity levels of various proteins. In the present study, quantitative changes of ryanodine receptors and the dihydropyridine receptors, and the functional consequences of these changes in various thyroid states were investigated. In hyperthyroid hearts, $[^3H]ryanodine$ binding and ryanodine receptor mRNA levels were increased, but protein levels of ryanodine were not changed significantly. However, the above parameters were markedly decreased in hypothyroid hearts. In case of dihydropyridine receptor, there were a significant increase in the mRNA and protein levels, and [3H]nitrendipine binding, whereas no changes were observed in these parameters of hypothyroid hearts. Our findings indicate that hyperthyroidism is associated with increases in ryanodine receptor and dihydropyridine receptor expression levels, which is well correlated with the ryanodine and dihydropyridine binding. Whereas opposite changes occur in ryanodine receptor of the hypothyroid hearts.

• Journal of Microbiology and Biotechnology
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• v.25 no.8
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• pp.1371-1379
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• 2015

The Ca_v1.2 Ca²⁺ channel is essential for cardiac and smooth muscle contractility and many physiological functions. We mutated single, double, and quadruple sites of the four potential Asn (N)-glycosylation sites in the rabbit Ca_v1.2 into Gln (Q) to explore the effects of Nglycosylation. When a single mutant (N124Q, N299Q, N1359Q, or N1410Q) or Ca_v1.2/WT was expressed in Xenopus oocytes, the biophysical properties of single mutants were not significantly different from Ca_v1.2/WT. In comparison, the double mutant N124,299Q showed a positive shift in voltage-dependent gating. Furthermore, the quadruple mutant (QM; N124,299,1359,1410Q) showed a positive shift in voltage-dependent gating as well as a reduction of current. We tagged EGFP to the QM, double mutants, and Ca_v1.2/WT to chase the mechanisms underlying the reduced currents of QM. The surface fluorescence intensity of QM was weaker than that of Ca_v1.2/WT, suggesting that the reduced current of QM arises from its lower surface expression than Ca_v1.2/WT. Tunicamycin treatment of oocytes expressing Ca_v1.2/WT mimicked the effects of the quadruple mutations. These findings suggest that Nglycosylation contributes to the surface expression and voltage-dependent gating of Ca_v1.2.

• The Korean Journal of Pharmacology
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• v.13 no.1 s.21
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• pp.7-12
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• 1977

Recently several reports have claimed that the bath temperature changes, such as lower bath temperature, produce supersensitivity on the positive chronotropic effect of catecholamine in cat, mouse and guinea pig atria. However, others showed controversial results against temperature-dependent supersensitivity. Similarly, the inotropic effect of ouabain is diminished in febrile state, however some investigators indicated that cardiac glycoside showed less toxicities and less effects in hypothermic condition. In this study, the effects of norepinephrine and epinephrine on inotropy and chronotropy in isolated rat atria was investigated by changing the temperature of bath ($30^{\circ}C$, $^35{\circ}C$ and $38^{\circ}C$). In addition, the effects of ouabain on atria in hypothermic bath was also studied. The followings are the results. 1. At the lower bath temperature isolated rat atrial rate was decreased and contractility was increased. 2. The chronotropic responses to norepinephrine and epinephrine in $38^{\circ}C$ were decreased when the bath temperature lowered to $35^{\circ}C$ or $30^{\circ}C$, while the inotropic responses were not affected. 3. Hypothermic supersensitivity to norepinephrine or epinephrine was not observed in rat atrium. 4. The inotropic response to ouabain was potentiated but chronotropic response was diminished by a lowering in the bath temperature. In conclusion, the chronotropic response of rat atrium to catecholamine was decreased, however, hypothermic supersensitivity was no longer present in rat atrium and the inotropic response of ouabain was increased at lower bath temperature.

• Journal of Veterinary Clinics
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• v.32 no.5
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• pp.422-425
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• 2015

This study evaluated the myocardial performance on echocardiography after the sedation/anesthesia of medetomidine (D), the combination of medetomidine and tiletamine/zolazepam (DZ), and the combination of medetomidine, tiletamine/zolazepam and tramadol (DZT) in Beagle dogs. Ten healthy adult Beagle dogs (weighing $8.6{\pm}1.0kg$) were enrolled in this study. Heart rate (HR), fractional shortening (%FS), left ventricular ejection fraction (%LVEF), stroke volume (SV), cardiac output (CO), left ventricular internal diameter in systole (LVIDs) and left ventricular internal diameter in diastole (LVIDd) using M-mode echocardiography were measured prior to anesthesia, then every 10 min for 60 min. The HR, %FS, %LVEF, SV and CO were significantly decreased during sedation/anesthesia with D, DZ and DZT combination of anesthesia. Although those anesthetic protocols provided acceptable quality of sedation/anesthesia, levels of cardiovascular suppression were substantial and persistent and thus the continuous monitoring on vital signs should be accompanied in any situation. Close attention is required for dogs with pre-existing heart diseases, when those anesthetic protocols were applied.