• Archives of Pharmacal Research
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• 제28권8호
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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.

• 인터넷정보학회논문지
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• 제12권2호
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• pp.9-17
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• 2011

본 논문은 유비쿼터스 홈 네트워크 시스템에서 저장된 사용자 행동 프로파일 데이터에 은닉 마르코프 모델에 적용하여 사용자의 행동 상태를 예측하는 알고리즘을 제안한다. 은닉 마르코프 모델은, 순차 데이터를 갖는 패턴을 인식하기 위해서 데이터에 내포되어 있는 시간성을 적절히 표현하고, 그것으로부터 원하는 정보를 추론할 수 있는 대표적인 모델이다. 제안 알고리즘에서는 "행동 인지 시스템(Activity Recognition System)"에 의하여 저장된 행동 발생 횟수, 행동 지속시간, 행동이 발생된 위치 데이터를 학습 데이터로 이용하였다. 사용자의 행동에 가중치를 부여하여 사용자의 행동에 대한 흥미를 객관적으로 수식화 하는 방법을 제안하였으며 은닉 마르코프 모델을 이용하여 시간에 따른 가중치 변화를 구하여 사용자의 행동 상태 변화를 예측하였다. 제안 알고리즘은 현실적인 유비쿼터스 홈 네트워크 구축에 도움을 준다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.126.2-127
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• 2003

The therapeutic potential of currently available antiarrhythmic drugs is limited by their tendency to induce proarrhythmic and extracardiac side effects. An ideal antiarrhythmic agent would selectively prolong the action potential duration more in extraordinarily depolarized cardiac myocytes than in normal cells. and show tissue selectivity. Voltage-gated K+ (Kv) channels represent a structurally and functionally diverse group of membrane proteins. (omitted)

• The Korean Journal of Pain
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• 제1권1호
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• pp.64-73
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• 1988

Recent studios have shown that narcotic drags produce an unusually intense, prolonged and segmental analgesic action in man whoa injected into the spinal subarachnoid or epidural space (Wang et al, 1979; Behar et al, 1979; Cousins et al, 1979; Magora et a., 1980, Johnston and McCaughey, 1980). Since 1960, many investigators claimed that low molecular weight(LMW) dextran increased the clinical duration of lidocaine(Loder, 1960; Loder, 1962), tetracaine (Chinn and Wirjoatmadja, 1967) and bupivacaine(Kaplan et al, 1975) in man but the mechanism of the action of dextran was unclear. But Curtiss and Scurlock(1979), and Buckled and Fink(1979) claimed that LMW dextran has no effect on the duration of action of bupivacaine in animal studies. The present study was performed to evaluate the clinical efficacy of analgesia by the thoracic epidural injection of morphine and bupivacaine mixture for the relief of pain due to fractured or contused ribs, to evaluate the duration of analgesic effect by the use of the above mixture in a hypertonic solution(dextran 70 or 50% dextrose in water) and to observe the possibility of improvement in the lung function after the pain block. The complications following the pain block were also observed. The 50 single thoracic epidural injections of the mixture were divided into three groups : Group 1(n=15) served as a control group and drags used for the relief of pain were as follows(Mean$\pm$S.D.): morphine($2.13{\pm}1.64\;mg$), 0.5% bupivacaine($3.10{\pm}1.04\;ml$) and 0.9% saline($3.64{\pm}1.11\;ml$). Group 2(n=16) serves as an experimental group and drugs were as follows(Mean$\pm$S.D.): morphine($2.13{\pm}0.72\;mg$), 0.5% bupivacaine($3.06{\pm}0.77\;ml$) and dextran 70($3.75{\pm}1.29\;ml$). Group 3 (n=19) served as an experimental group and drags were as follows(Mean$\pm$S.D.) : morphine($2.42{\pm}0.51\;mg$), 0.5% bupivacaine($3.21{\pm}0.71\;ml$) and 50% dextrose in water($3.58{\pm}1.11\;ml$). The results are were follows: 1) The Dumber of patients who obtained excellent and good analgesic effects following the block were greater in the experimental Croup 2(94%) and Group 3 (90%) than theme of the control Group 1 (80%). 2) The duration of pain relief which lasted more than 3 days after the epidural block was longer in the experimental Group 2 (81%) and Group 3 (75%) than those of the control Croup 1(67%). 3) The pulmonary reserve(FVC%+FEV 1.0%) of 27 cases who were treated by the pain block between 1 and 31 drys following the chest injury was increased to about 13% than those before the block, and that of 13 cases between 32 and 82 days following the chest injury was decreased to about 4% than those before the block. 4) Of the complications following the pain block, there were 5 cased(10%) of nausea within 2 hours following the block, 4 cases(8%) of vomiting after 2 hours following the block, 10 cases(20%) of pruritus after 3~4 hours following the block, 17 cases(34%) of transient urinary retention which tasted 8 to 19 hours, 3 cases(6%) of headache within 2 hoers following the block and 2 cases(4%) of dural puncture. In conclusion, it is suggested that the clinical duration of analgesic effect produced by morphine and bupivacaine mixture can be prolonged by addition of the hypertonic solution to the mixture.

• The Korean Journal of Physiology
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• 제21권1호
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• pp.1-12
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• 1987

There is evidence that the effect of extracellular $Ca^{2+}$ on heart rate is temperature-dependent: at $38^{\circ}C$ excess $Ca^{2+}$ induces positive chronotropic response, whereas at $30^{\circ}C$ there is no significant chronotropic effect of $Ca^{2+}$. The cause of this temperature-dependency, however, remains still unclear. Therefore, this study was undertaken to investigate the chronotropic effect of external $Ca^{2+}$ at different temperature in the isolated rabbit atria and in the small strips of SA node cut perpendicularly to crista terminalis. In the isolated atria, the $Ca^{2+}$ effect was temperature-dependent: at $35^{\circ}C$ excess $Ca^{2+}$ evoked positive chronotropic response, while at $30^{\circ}C$ there was no significant changes in sinus rate. On the contrary, in the small SA strips external $Ca^{2+}$ induced negative chronotropic effect. At $35^{\circ}C$ changes in $Ca^{2+}$ concentration from 2 to 4, 6, and 10 mM decreased the sinus rate by $2.7{\pm}1.6%$, $11.2{\pm}3.7%$ and $23.2{\pm}8.1%$ respectively. Lowering the temperature to $30^{\circ}C$, the negative chronotropic effect of $Ca^{2+}$ became greater. With intracellular microelectrodes transmembrane potential was recorded in the small SA strips at $30^{\circ}C$, $35^{\circ}C$ and $38^{\circ}C$. As temperature increased from 30 to $38^{\circ}C$, sinus rate was accelerated by $13/min/^{\circ}C$, $APD_{50}$(action ptential duration from peak to 50% repolarization) decreased by $5\;msec/^{\circ}C$, and amplitude of action potential was slightly decreased. With an increase in $Ca^{2+}$ concentrations from 0.5 to 6 mM, overshoot increased and MDP decreased. These $Ca^{2+}$ effects on the overshoot and MDP of action potentials were not altered by temperature. But the $Ca^{2+}$ effects on the rates of diastolic depolarization, systolic depolarization and repolarization were modified by temperature. Discrpancy of the chronotropic effects of $Ca^{2+}$ between isolated atria and small SA strips was discussed.

• The Korean Journal of Physiology
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• 제16권1호
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• pp.13-23
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• 1982

Effects of external pH and potassium concentrations on the electrical and mechanical properties were investigated on rabbit papillary muscle. Papillary muscles were perfused in horizontal chamber with Tris Tyrode solutions and action potential along with isometric tension was recorded simultaneously. Potassium concentrations were varied between 1 and 12 mM at low(6.9), normal(7.4) and high (7.9) external pH. The following results were obtained: 1) On rasing the potassium concentration from 1 to 12 mM resting membrane potentials decreased from $-88.8{\pm}2.8$ to $-66.4{\pm}1.2\;mV$ at normal pH and the amplitude of action potential decreased from $115.1{\pm}0.7$ to $97.5{\pm}2.8\;mV$. On lowering the potassium concentration, membrane hyperpolarized and at 1 mM potassium concentration resting potentials were $-107{\pm}2.2\;mV$. Duration of action potential especially $APD_{60}{\sim}APD_{90}$ increased($APD_{90}$: $214{\pm}15.8\;ms$ at 1 mM $K^+$ to $287{\pm}18.1\;ms$ at 12 mM $K^+$). 2) During acidosis membranes hyperpolarized by more than 20 mV within 1 min. and then slow recovery was observed during the following 10 min. During alkalosis membranes depolarized about 10 mV, which were maintained until washing with normal Tyrode solutions. 3) On lowering the external pH(7.9-6.5), duration of action potential increased progressively and it was most prominent at pH 6.5 and $K^+$ 1mM. 4) Magnitude of developed tension was $0.6{\pm}0.14\;g/mm^2$ at normal pH and potassium concentration (stimulus frequency : 60/min). Relative isometric tension to normal value increased along the increment of stimulus frequency($44.2{\pm}4.2%$ at 6/min to $271{\pm}86.7%$ at 180/min). Force-frequency relations were altered quantitatively during the perfusion with different external pH solutions. 5) Developed tension did not show marked variation within the range of $2{\sim}8\;mM$ potassium concentrations. Positive inotropism was observed at less than 2 mM $K^+$ and negative inotropism beyond 12 mM $K^+$ concentrations. From the above results we concluded that the effects of potassium ion concentration on electrical and mechanical properties of rabbit papillary muscle are related to the changes in surface negative charge due to acid base disturbances.

• The Korean Journal of Physiology
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• 제17권2호
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• pp.169-176
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• 1983

It is well known that the acupuncture has been used effectively for the relief of certain types of pain. Although the precise mechanism of action of acupuncture analgesia is unknown, it is generally accepted that their analgesic properties are related to the activation of endogenous opiate system in central nervous system. And it is suggested that pain-relieving properties of acupunture may be related to a stimulation of peripheral nerve underlying the acupuncture point on the skin. However, the efficacy of acupuncture has no relationship between the site of pain and the acupuncture point. Consequently, the present study was undertaken to investigate electroacupuncture analgesia in relation to the site of peripheral nerve stimulation. Cats were decerebrated ischemically and the flexion reflex as an index of pain was elicited by stimulating the sural nerve (20V, 0.5 msec duration) and recored as a compound action potential from the nerve innervated to the posterior biceps femoris muscle in the ipsilateral hindlimb. Bilateral common peroneal nerve and contralateral superficial radial nerve were selected as the site of peripheral nerve stimulation. For the stimulation of peripheral nerve, a stimulus of 20 V intensity, 2 msec-duration and 2 Hz-frequency was applied for 60 min respectively. The results obtained are summarized as follows: 1) Both stimulation of contralateral common peronal nerve and contralateral superficial radial nerve did not change the flexion reflex and there were no significant differences between them. 2) Stimulation of ipsilateral common peroneal nerve markedly depress the flexion reflex, the effect being reversed by naloxone application. These results suggest that stimulation of ipsilateral common peroneal nerve has the analgesic effect but both stimulation of contralteral common peroneal nerve and contralateral superficial radial nerve to the pain site where flexion reflex was elicited have no analgesic effect.

• Journal of Dental Anesthesia and Pain Medicine
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• 제18권3호
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• pp.143-149
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• 2018

Background: We evaluated the changes in mean arterial pressure (MAP) and heart rate (HR), and the anesthetic and hemostatic effects, after injection of 2% lidocaine containing various concentrations of epinephrine in rats and mice to determine the appropriate concentration of epinephrine in various anesthetic mixtures. Methods: Rats and mice were randomly allocated to experimental groups: 2% lidocaine without epinephrine (L0), 2% lidocaine with epinephrine 1:200,000 (L200), 1:100,000 (L100), and 1:80,000 (L80). Changes in MAP and HR after administration of the anesthetic mixture were evaluated using a physiological recording system in rats. Onset and duration of local anesthesia was evaluated by pricking the hind paw of mice. A spectrophotometric hemoglobin assay was used to quantify the hemostatic effect. Results: MAP increased in response to epinephrine in a dose-dependent manner; it was significantly higher in the L80 group than in the L0 group at 5 min post-administration. The HR was relatively lower in the L0 group than in the L80 group. The time required for onset of action was < 1 min in all evaluation groups. The duration of action and hemostatic effect of the local anesthetic were significantly better in the L200, L100, and L80 groups than in the L0 group. Conclusion: L200 demonstrated relatively stable MAP and HR values with satisfactory efficacy and hemostatic effect. L200 might be a better local anesthetic for dental patients in terms of anesthetic efficacy and safety.

• Toxicological Research
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• 제24권4호
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• pp.289-295
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• 2008

Toxicology screening following treatment with astemizole, a histamine receptor antagonist, at oral doses of 0, 10, 30 and 60 mg/kg was carried out in male cynomolgus monkeys (Macaca fascicularis). No dose-related changes in mortality, clinical signs, body weight changes, food consumption, or urine analysis occurred in any animal compared to the vehicle control. However, the high-dose group showed a decrease in BUN and ALP compared to vehicle control group. In addition, the levels of TG, AST, ALP and CK increased. Although astemizole did not produce significant toxicological changes at any dose tested, we predict that it can cause toxicological changes of the liver and heart based on the changes in the serum parameters related to the heart and liver. The Action Potential Duration (APD) was prolonged in the heart of 60 mg/kg treatment group compared to the control group. The APD increase in 60 mg/kg treatment group along the other related changes in toxicological parameters imply that astemizole has major cardiotoxic effects in the cynomolgus monkey. This study is a valuable assessment for predicting the general toxicity and cardiotoxic effects of antihistamine drugs using nonhuman primates.

• Journal of Sport and Applied Science
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• 제7권2호
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• pp.39-51
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• 2023

Purpose: The purpose of this study was to investigate differences in the control process to satisfy spatial and temporal constraints imposed upon the anticipation timing response by analyzing the effect of spatio-temporal accuracy demands on eye movements, response accuracy, and the coupling of eye and hand movements. Research design, data, and methodology: 12 right-handed male subjects participated in the experiment and performed anticipation timing responses toward a stimulus moving at three velocities (0.53m/s, 0.66m/s, 0.88m/s) in two task constraint conditions (temporal constraint, spatial constraint). During the response, response accuracy and eye movement patterns were measured from which timing and radial errors, the latency of saccade, fixation duration of the point of gaze (POG), distance between the POG and stimulus, and spatio-temporal coupling of the POG and hand were calculated. Results: The timing and radial errors increased with increasing stimulus velocity, and the spatio-temporal constraints led to larger timing errors than the temporal constraints. The latency of saccade and the temporal coupling of eye and hand decreased with increasing stimulus velocity and were shorter and longer respectively in the spatio-temporal constraint condition than in the temporal constraint condition. The fixation duration of the POG also decreased with increasing stimulus velocity, but no difference was shown between task constraint conditions. The distance between the POG and stimulus increased with increasing stimulus velocity and was longer in the temporal constraint condition compared to the spatio-temporal constraint condition. The spatial coupling of eye and hand was larger with the velocity 0.88m/s than those in other velocity conditions. Conclusions: These results suggest that differences in eye movement patterns and spatio-temporal couplings of stimulus, eye and hand by task constraints are closely related with the accuracy of anticipation timing responses, and the spatial constraints imposed may decrease the temporal accuracy of response by increasing the complexity of perception-action coupling.