Interlaboratory method validation of slope ratio determination for anticoagulant activity of leeches / 中国药理学通报

Aim To investigate the slope ratio method for the determination of anticoagulant activity of leeches. Methods Three batches of leeches, four groups of Japanese medical vermiculite yinpian and fifteen groups of leech preparations were chosen, with contrast medicinal leeches herbs and Philippine cattle leech contrast medicinal materials, and different concentrations of leaching solutions were prepared in parallel. APTT value was determined after anticoagulant activity was determined by slope ratio method for the joint validation of laboratory, intermediate precision and accuracy between the linear range. Results The slope ratio method was accurate and accurate in the determination of anticoagulant activity of leeches, with linearity between 64% and 156% relative titer level. Conclusion Slope ratio method can be used to determine the anticoagulant activity of leeches.

Interim In vitro Dose-Response Curve for the Dicentric Biodosimeter Assay from a Philippine Radiotherapy Facility using a Linear Accelerator

@#Background. Accidental radiation exposure can occur anytime. Biodosimeters help in quantifying the absorbed dose of individuals who are not equipped with personal dosimeters during radiation exposure. The dicentric assay can quantify radiation damage by correlating radiation dose exposure with the frequency of dicentric chromosomes in the peripheral lymphocytes extracted from exposed individuals. Objective. The study aims to present the interim results of the reference dose-response curve for a Philippine radiotherapy facility constructed using a 6MV linear accelerator (ClinacX, Varian). Methods. Samples of peripheral blood from healthy volunteers were irradiated in a customized water phantom of doses 0.10 to 5.0 Gray using a linear accelerator. The irradiated samples were cultured and analyzed following the International Atomic Energy Agency Cytogenetic Dosimetry Protocol (2011) with modifications. Linear-quadratic model curve fitting and further statistical analysis were done using CABAS (Chromosome Aberration Calculation Software Version 2.0) and Dose Estimate (Version 5.2). Interim results of the samples were used to generate these curves. Results. The dose-response curve generated from the preliminary results were comparable to published dose response curves from international cytogenetic laboratories. Conclusion. The generated dose-response calibration curve will be useful for medical triage of the public and radiologic staff accidentally exposed to radiation during medical procedures or in the event of nuclear accidents.

Establishment and validation of the dose-response curve of X-rays irradiation and chromosome aberrations in human peripheral blood cells / 中国职业医学

OBJECTIVE: To explore the dose-effect of X-ray irradiation and chromosome aberrations in human peripheral blood cells,and establish a dose-response curve of dicentric and ring(dic+r)aberration induced by X-ray irradiation.METHODS: Human peripheral blood samples were collected from three healthy individuals and were exposed to X-ray at the doses of 0.00,0.25,0.50,0.75,1.00,2.00,3.00,4.00 and 5.00 Gy in vitro.The dose rate was 1.158 Gy/min.The blood cells were harvested after routine culture,and the chromosome preparation was carried out.The dicentrics and rings in metaphase cells were counted under microscope,and a dose-response curve was fitted by using the software of CABAS.Dose estimation was performed according to the curve from two blind samples.RESULTS: Aberration of dic+r increased with irradiation doses in the range of 0.00-5.00 Gy(P<0.01).The dose-response relationship followed a linear-quadratic equation:■,where■ is the yield of dic+r,and D is the irradiated dose.The estimated doses of the two blind samples were in accordance with the actual doses.CONCLUSION: The dose-response curve and mathematical model of chromosome aberration following exposure to 0.00-5.00 Gy X-ray irradiation is established in this study provide a reliable method for the accurate dose estimation.

Effects of obesity on dose-response curve of rocuronium in female patients / 临床麻醉学杂志

Objective To observe the effects of obesity on dose-response curve of rocuronium in female patients and calculate ED9 5 of rocuronium.Methods Eighty female patients,aged 18-45 years, falling into ASA grade Ⅰ or Ⅱ,schedualed for elective surgery under general anesthesia,undergoing surgery less than 1.5 h,were included in the study.The patients with body mass index of 20-25 kg/m2 as group N were randomized to divided group N1,group N2,group N3 and group N4.Anoth-er 40 patients with body mass index of 30-35 kg/m2 as group B were randomized to divided group B1, group B2,group B3 and group B4.When the first twitch height of TOF (T1)was 100%,groups N1-N4 and groups B1-B4 patients were injected rocuronium 0.075,0.1,0.1 5,0.3 mg/kg respectively. The first dose of rocuronium in each group,T1 maximum inhibition degree and onset time were re-corded.The relationship between probit-transformed depression of T1 and the logarithm dose of rocu-ronium was analyzed by linear regression.ED50 and ED9 5 of rocuronium in obese and normal body weight patients were calculated.Results Dose-response curve equation of each group were Y1 =3.464X1 -2.23 and Y2 = 3.843X2 - 2.750 respectively(P < 0.05 ).The ED50 and ED9 5 (95% CI)of rocuronium were 0.122 (0.092-0.1 65 )mg/kg and 0.324 (0.242-0.433 )mg/kg in group N,and were 0.103 (0.078-0.133)mg/kg and 0.25 1 (0.1 93-0.326)mg/kg in group B.Conclusion Obesity significantly affects the dose-response curve of young women and can enhance the sensitivity of them to the rocuronium.The ED9 5 of obese patients is 0.25 1 mg/kg.

Establishing dose-response curve of chromosome aberration induced by in vitro X-ray irradiation in human peripheral blood / 中国职业医学

OBJECTIVE: To establish the dose-response curve of chromosome aberration induced by X-ray irradiation in human peripheral blood in vitro. METHODS: The median cubital vein blood of healthy male donors were collected and irradiated with X-ray at the dose of 0. 00-5. 00 Gy in vitro. The dose rate was 0. 8 mGy/s. The cells were cultured with colchicine and stained with routine Giemsa staining. The slices were blindly examined. The morphology of chromosomes were recorded as dicentric,multi-centric,dicentric plus rings or fragments( hereinafter referred to as dicentric + ring) in metaphase cells. The occurrence of dicentric + ring and the irradiation dose was used to create the dose-response curve.RESULTS: The results showed that the occurrence of dicentric + ring in abnormal cells increased with the increasing irradiation dose in the range of 0. 00-5. 00 Gy( P < 0. 01). The best fitting equation of 0. 00-1. 00 Gy is y = 23. 22 D2+4. 768 D-0. 018( P < 0. 01). The best fitting equation of 0. 50-5. 00 Gy is y = 34. 23 D-3. 072( P < 0. 01).CONCLUSION: The fitting degree of dose-response curve is good,which can be used as reference in laboratory to assess irradiation exposure dose.

Study on quality control methods of Fuzheng Xiaoji capsule based on biological detection method / 中国生化药物杂志

Objective To establish biological detection method for Fuzheng Xiaoji capsule.MethodsTaken Radix astragali,Hedyotis diffusa Willd, Fructus Polygoni orientalis and rhubarb in Fuzheng Xiaoji capsule as targets, the antimicrobial activity of the single fried mixture of Radix astragali,Hedyotis diffusa Willd,Fructus Polygoni orientalis and rhubarb to 4 kinds of standard strains(Staphylococcus aureus, Salmonella, Escherichia coli and Bacillus subtilis) were inspected.The standard curve by susceptible strains of the inhibition zone diameter and logarithm of the concentration was established,and this test also determined the biological potency of different batches of Fuzheng Xiaoji capsule according to the dose-response curve.ResultsThe single fried mixture of Radix astragali,Hedyotis diffusa Willd, Fructus Polygoni orientalis and rhubarb have strong anti-bacterial effect to the above four standard strains.There was a good linear relationship between logarithmic dose and response effect when the concentration in the range of 0.029-0.136g/mL(r=0.9583).ConclusionBiological potency detection method can be combined with traditional analysis methods to control the quality of Fuzheng Xiaoji capsule.

Potency Determination of Lonicera Granule Based on Bacterial Inhibitory Activity / 中国药师

Objective:To explore the chemical-biological evaluation pattern for the quality control and evaluation of Chinese materia medica solid preparations( CMMSP) according with the characteristics of Chinese traditional medicines. Methods:Lonicera granule as the model drug, the bacteria sensitive tests [minimal inhibitory concentration (MIC) and minimal bactericidal concentration(MBC)] were applied to study the antimicrobial effect of Lonicera extract on 4 kinds of standard strains ( Staphylococcus aureus, Streptococcus pneumoni-ae, Escherichia coli and Pseudomonas aeruginosa). The standard curves of the relationship between the anti-bacterial ring diameter for sensitive bacterial and the concentration of Lonicera extracts were established, and the biological potency of Lonicera granule from differ-ent manufacturers was calculated and compared with the result of the HPLC method ( measured by chlorogenic acid) . Results:The anti-microbial test showed that Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and Pseudomonas aeruginosa were susceptible to Lonicera, and the antibacterial circle edge for Staphylococcus aureus was clear with higher sensitivity. There was a good linear relation-ship between the logarithmic dose and the response effect when the concentration of Lonicera was within the range of 0. 014 2-0. 068 0 g· ml-1(r=0.990 9). Conclusion:As a quality control method for Lonicera and Lonicera granules, the bioassay is feasible, which can ef-fectively cooperate with the traditional test method for the quality control of Lonicera and its preparations.

Investigating the dose-response curves of cisatracurium in the different gender epileptics / 临床麻醉学杂志

Objective To evaluate the gender differences in dose-response curve with cisatra-curium in epileptics.Methods Eighty ASA grade Ⅰ or Ⅱ epileptics were enrolled in this study.All patients were divided into male and the female groups and received the method of single dose injection under midazolam-fentanyl intravenous anesthesia.Each patient received intravenous bolus of 20,30, 40,50μg/kg of cisatracurium respectively.The neuromuscular block was measured by Neuromuscular Transmission Monitor and the responses were defined in terms of the percentages of maximum sup-pression in T1 of TOF of the adductor pollicis muscle.According to log-probit transformation of the data of dose and response,the dose-response curve of cisatracurium was established through linear re-gression.The onset time of cisatracurium was also observed.Results The ED50 ,ED75 ,ED90 ,ED95 values of cisatracurium in male epilepsy patients were 37.2±9.7,48.1±11.3,60.4±12.8,69.3± 14.0 μg/kg and that of female epilepsy patients were 36.6±4.3,47.5±7.7,60.5±14.0,70.1± 19.4 μg/kg.There was no significant difference between the two gender groups.No significant change in onset time was observed among 4 dose groups.Conclusion No gender differences are ob-served in dose-response curve of cisatracurium in epileptics.

Effects of Nimodipine on Dose-Response Curves of Vecuronium, Rocuronium, and Atracurium Using Phrenic Nerve-Diaphragm Preparations of Rats / 대한마취과학회지

BACKGROUND: Interactions between nimodipine, a calcium channel blocker, used perioperatively for the treatment of subarachnoid hemorrhage, and vecuronium, rocuronium, and atracurium were studied with phrenic nerve-hemidiaphragm preparations of rats. METHODS: Male 200-300 g Sprague-Dawley rats were randomly allocated into four groups (control, NMD(5), NMD(50) and NMD(500) group, n = 10, respectively) according to the nimodipine concentration, and three groups (control, NMD(2D) and NMD(7D), n = 10, respectively) according to the pretreatment duration. A square wave 0.1 Hz supramaximal stimuli was applied to the phrenic nerve-hemidiaphragm preparation and the twitch height response was recorded with mechanomyography. The dose-response curves were measured, and ED(5), ED(50), ED(90), and ED(95) of each vecuronium, rocuronium, and atracurium in different concentrations of nimodipine of 5, 50, and 500 ng/ml and rocuronium in pretreatment with nimodipine 2.5 mg/kg/d for 2 and 7 days were calculated using an inhibitory sigmoid Emax model. RESULTS: The dose-response curves of rocuronium and atracurium were significantly shifted to the left in NMD(500) group, and significantly shifted to the right in NMD(7D) group (P < 0.05). In NMD(500) group, ED(50), ED(90), and ED(95) of rocuronium and atracurium were significantly reduced, and those of rocuronium in NMD7D group were significantly increased compared with the control group (P < 0.05). CONCLUSIONS: Nimodipine 500 ng/ml in the phrenic nerve-hemidiaphragm preparation of rat increased sensitivity to rocuronium and atracurium, and the dose-response curve was significantly shifted to the left, but following pretreatment for 7 days, nimodipine decreased the potency of rocuronium, and the dose-response curve was significantly shifted to the right.

Effects of Phenytoin on Rocuronium-induced Neuromuscular Blockade Using a Rat Phrenic Nerve-diaphragm Preparation / 대한마취과학회지

BACKGROUND: Chronic anticonvulsant therapy with phenytoin antagonizes the action of nondepolarizing muscle relaxants. Rocuronium is a new non depolarizing muscle relaxant of rapid onset and intermediate duration. This study was designed to investigate the effects of phenytoin on rocuronium-induced neuromuscular blockade using a rat phrenic nerve-diaphragm preparation. METHODS: Male Sprague-Dawley rats (200 g, n = 70) were randomly allocated into a control group (C, n = 10), three phenytoin-pretreated groups (PP, n = 30) and three phenytoin-non-pretreated groups (PNP, n = 30). In phenytoin-pretreated groups, phenytoin 50 mg/kg/day was administered intraperitoneally once a day for one day (PP1D), seven days (PP7D) or twenty eight days (PP28D). Animals were anesthetized with 40 mg/kg of thiopental sodium intraperitoneally and the diaphragm with the phrenic nerve were dissected, and the phrenic nerve-diaphragm preparation was suspended in 100 ml of Krebs solution in an organ bath. The bath was aerated with 95% O2-5% CO2 at 32oC, and the phrenic nerve was stimulated with supramaximal intensity using a stimulator. Twitch responses were measured using a precalibrated force displacement transducer and recorded. The cumulative dose-response relationships of rocuronium and phenytoin were determined. After one hour's stabilization, rocuronium 100 microgram was added to the bath, and when a stable 3-5 twitch was obtained, incremental 50 microgram doses of rocuronium were added to obtain more than 95% neuromuscular twitch inhibition at 0.1 Hz. In the phenytoin-non-pretreated group, phenytoin was administered simultaneously with the initial dose of rocuronium to a phenytoin concentration of 1 microgram/ml (PNP1), 10 microgram/ml (PNP10), or 100 microgram/ml (PNP100) in Krebs solution. Data were analyzed by probit and logistic models. In the PP group, the plasma concentration of phenytoin was analyzed by high performance liquid chromatography. RESULTS: The dose-response curve of rocuronium was significantly shifted to the left in the PNP100 group (P < 0.05), and significantly shifted to the right in the PP28D group (P < 0.05). The plasma phenytoin concentration was found to be directly proportional to the duration of the phenytoin pretreatment. CONCLUSIONS: The potency of rocuronium is reduced in chronic phenytoin therapy and increased after an acute high dose of phenytoin.

Effects of Dexamethasone on Neuromuscular Transmission in a Phrenic Nerve-Hemidiaphragm Preparation in the Rat / 대한마취과학회지

BACKGROUND: MacFarlane and Rosenthal reported a case of acute quadriplegia after nondepolarizing muscular blocking agents in status asthmaticus patient treated with high doses of corticosteroid. Reports regarding the reactions of glucocorticoid treated muscles to neuromuscular blocking agents are sparse and inconsistent. The aims of this study were to examine the degree of muscle atrophy and its effects on sensitivity to neuromuscular blocking agents in relation to the dose and duration of dexamethasone. METHODS: Sixty Sprague-Dawley rats were divided into six groups. They were treated daily with dexamethasone 0.4 mg/kg and 4 mg/kg daily for 1 week or 3 weeks. The two control groups were treated with normal saline. The day after treatment, the dose-response curves of vecuronium were measured using a phrenic nerve-hemidiaphragm preparation. To classify muscle fiber, the diaphragm was stained for myofibrillar adenosine triphosphatase after alkaline and acid preincubation, and a morphometric examination was carried out. RESULTS: The diaphragmatic muscle in rats treated with long term, high dose dexamethasone showed significant atrophy. For the short term, low dose dexamethasone group, the ED50 and ED95 of vecuronium decreased 41.5% and 26.8% compared to those of the control group, respectively (P<0.05). However, the ED50 of vecuronium in the long term, high dose dexamethasone group increased 22.2% compared to that of the control group (P<0.05). CONCLUSION: This study suggests that sensitiviy to vecuronium was not modulated by dexamethasone-induced muscle atrophy. Quantitative changes of receptors at the neuromuscular junction or some anoother process might be responsible for this change.

Effects of berberine on left atria and trachea in guinea pigs / 中国临床药理学与治疗学

AIM: To observe the effects of berberine (Ber) on left atria and trachea in guinea pigs. METHODS: The experiment was carried out with isolated left atria and trachea in guinea pigs, and the effects and interactions were compared between Ber and pinacidil (Pin). RESULTS: Ber concentration-dependent increased the force of contractile, while Pin decreased the force. Ber leaded a parallel rightward shift in accumulated response curve of depression contraction of left atria by Car, and it hardly changed the maximum response (E_(max)), while Pin leaded a parallel leftward shift in the same curve. In the combination of Ber and Pin, the dose-response curve hardly changed as the control one. In isolated guinea pig trachea, Ber caused a leftward shift in the dose-response curve of ACh, whereas Pin produced a rightward shift in the same curve without changing E_(max). When both Ber and Pin existed in the same container, there was no modification in the response to ACh. CONCLUSION: Ber shows the effect of blocking potassium channel.

Clinical Impact of Bronchial Reactivity and Its Relationship with Changes of Pulmonary Function After Asthmatic Attack Induced by Methacholine / 결핵

BACKGROUND: Bronchial reactivity is known to be a component of airway hyperresponsiveness, a cardinal feature of asthma, with bronchial sensitivity, and is increments in response to induced doses of bronchoconstric tors as manifested by the steepest slope of the dose-response curve. However, there is some controversy regarding methods of measuring bronchial reactivity and clinical impact of such measurements. The purpose of this study was to evaluate the clinical significance and assess the clinical use by analyzing the relationship of the bronchial sensitivity, the clinical severity and the changes in pulmonary function with bronchial reactivity. METHOD: A total of 116 subjects underwent a methacholine bronchial provocation test. They were divided into 3 groups : mild intermittent, mild persistent, moderate and cough asthma. Severe patients were excluded. Methacholine PC20 was determined from the log dose-response curve and PC40 was determined by one more dose inhalation after PC20. The steepest slope of log dose-response curve, connecting PC20 with PC40, was used to calculate the bronchial reactivity. Body plethysmography and a single breath for the DLCO were done in 43 subjects before and after methacholine test. RESULTS: The average bronchial reactivity was 38.0 in the mild intermittent group, 49.8 in the mild persistent group, 61.0 in the moderate group, and 41.1 in the cough asthma group. There was a weak negative correlation between PC20 and bronchial reactivity. A heightened bronchial reactivity tends to produce an increased clinical severity in patients with a similar bronchial sensitivity and basal spirometric pulmonary function. There were significant correlations between the bronchial reactivity and the initial pulmonary function before the methacholine test in the order of sGaw, Raw, FEV1/FVC, MMFR. There were no correlations between the bronchial sensitivity and the % change in the pulmonary function parameters after the methacholine test. However, there were significant correlations between the bronchial reactivity and the PEF, FEV1, DLCO. CONCLUSION: There was weak significant negative correlation between the bronchial reactivity and the bronchial sensitivity, and the bronchial reactivity closely reflected the severity of the asthma. Accordingly, measuring both the bronchial sensitivity and the bronchial reactivity can be of assistance in assessing of the ongoing disease severity and in monitoring the effect of therapy.

Effects of Lidocaine on the Dose-Response Curve of Cisatracurium / 대한마취과학회지

BACKGROUND: Lidocaine is useful as a local anesthetic and antiarrhythmic agent perioperatively. It may augment a neuromuscular block from both nondepolarizing and depolarizing muscle relaxants. Cisatracurium is a new muscle relaxant as an isomer of atracurium. We investigated the interaction of cisatracurium and lidocaine on the dose-response curve in vitro. METHODS: Institutional approvement was obtained. Forty male Sprague-Dawley rats (150 - 200 gm) were divided into four groups (control, lidocaine 0.01, 0.1, or 1ng/ml). The animals were anesthetized with 40 mg/kg pentobarbital. The hemidiaphragm with the phrenic nerve was dissected and mounted within 5 minutes in a bath containing 100 ml Kreb's solution at 32degreesC. The phrenic nerve was stimulated at supramaximal intensity by a Grass(R) S88 stimulator through an SIU5 isolation unit. A twitch height was measured by a precalibrated Grass FT88 force displacement transducer and recorded with a Grass 79 polygraph. After stabilization of the twitch response, cisatracurium was added to the solution to obtain an initial concentration of 50ng/ml with saline 1 ml or lidocaine 0.01, 0.1 or 1ng/ml. When a stable 3 - 5 twitch inhibition was obtained after the first dose, additional cisatracurium was added to the Kreb's solution in increments of 25ng/ml to more than a 90% neuromuscular block. The data was analyzed by repeated measures of ANOVA. RESULTS: There was a significant decrease in the effective dose of cisatracurium needed to depress the twitch response in lidocaine 0.1ng/ml and 1ng/ml groups compared with the control group and with the lidocaine 0.01ng/ml group. CONCLUSIONS: We concluded that lidocaine will increase the sensitivity to cisatracurium in the hemidiaphragm preparation of rats.

Effect of Duration of Lower Motor Neuron Injury on Mivacurium-induced Muscluar Relaxation in Rabbits / 대한마취과학회지

BACKGROUND: The purpose of this study was to investigate whether the effects of mivacurium on muscular relaxation were similar by the duration of more than 2 weeks after the injury of lower motor neurons in rabbits. METHODS: The animals were divided into five groups. The control group was without lower motor neuron injury. In the experimental groups, the lower motor neuron injury was made by denervating with 75 - 80% lesion on the common peroneal nerve to the right anterior tibialis muscle. The experimental groups were subdivided as 1, 2, 3 and 4 week groups (referred to ad the 1 wk, 2, 3 and 4 wks group) according to the durations of the denervation of common peroneal nerve, respectively. The dose-response relationship of mivacurium on the muscle twitches induced by TOF (train of four) stimulation (supramaximal stimulus of 0.2 ms duration, square-wave pulses, 2 Hz rate, repeated every 10 seconds) was studied by calculating ED50 and ED95 in the anterior tibialis muscles and compared between all groups. After recording the muscle twitches, microscopic findings were observed. RESULTS: The effective dose for 95% twitch depression (ED95) of mivacurium at 1week after denervation was significantly higher than that of the control group (P <0.05), but the ED95 of 2, 3 and 4wks groups were not significantly different from that of the control group. However, the ED95 of 3 and 4wks group were inclined to be lower than that of the control and significantly lower than 1wk group (P < 0.05). There was no significant difference in the effective dose for 50% twitch depression (ED50) of mivacurium in all groups. The size of the anterior tibialis muscle was significantly decreased at 4weeks after the lower motor neuron injury (P <0.05), but the number of its sarcoplasmic nuclei was increased, according to the duration after the denervation. CONCLUSIONS: Our results therefore suggest that neuromuscular response of denervated anterior tibial muscle was resistant to intravenous mivacurium in early periods of 1 or 2 weeks but sensitive 4 weeks after the lower motor neuron injury.

Neuromuscular Blocking and Vagolytic Effects of Atracurium, Cisatracurium, and Mivacurium in the Anesthetized Cat / 대한마취과학회지

BACKGROUND: Atracurium is a benzylisoquinolium nondepolarizing neuromuscular blocking drug. It releases histamine upon the rapid administration of more than 2 x ED95. Cisatracurium is about three to four times more potent than atracurium, less likely to release histamine, and has weaker cardiovascular or autonomic effects. Mivacurium releases histamine to about the same degree as atracurium at the same dose. This study was undertaken to reevaluate the experimental model for the evaluation of effects on the autonomic nervous system, and to determine the neuromuscular blocking profiles and the vagolytic effects of atracurium, cisatracurium and mivacurium in cats. METHODS: Cats, either sex, anesthetized with pentobarbital, were used. Neuromuscular blocking effects were assessed using the effects on the anterior tibialis muscle twitch evoked with supramaximal stimuli (0.2 ms-duration, 0.1 Hz). Inhibition of the parasympathetic nervous system was assessed in response to bradycardia to vagal nerve stimulation with ten-second trains of square-waves (0.5 ms-duration, 20 Hz). The dose-response curves for both neuromuscular blocking and vagolytic actions were determined for each animal. The dose-response curves were constructed in cumulative fashion. The response for vagal stimuli was measured two minute after each dosing. Vagal ID50 (The doses that produced 50% inhibition of the response to vagus nerve stimulation) were determined. RESULTS: NMB ED95 and NMB ED50, respectively, were 102.0 +/- 28.3 and 143.7 +/- 40.5 microgram/kg for atracurium, 81.4 +/- 13.3 and 110.7 +/- 18.8 microgram/kg for cisatracurium, and 56.8 +/- 17.4 and 74.2 +/- 25.0 microgram/kg for mivacurium. Vagal ID50 was 2,654 +/- 1,651 microgram/kg for atracurium, 655 +/- 389 microgram/kg for cisatracurium, and 606 +/- 182 microgram/kg for mivacurium. The vagal ID50/NMB ED95 and vagal ID50/NMB ED50 were 18.5 and 26.0 for atracurium, 5.9 and 8.1 for cisatracurium, and 8.2 and 10.7 for mivacurium. CONCLUSIONS: Atracurium has a wider margin of safety only for vagal stimulation as compared with cisatracurium and mivacurium. However, we couldn't exclude that either sympathetic stimulation or histamine release might contribute to heart rate.

Comparison of the Effects of Nitroglycerin and Nitroprusside on Hypoxic Pulmonary Vasoconstriction in the Isolated Rabbit Lung / 대한마취과학회지

BACKGROUND: It has been reported that two common vasodilators, nitroglycerin (NTG) and sodium nitroprusside (SNP), inhibit regional HPV and decrease arterial oxygenation as a result. The purpose of the present study was, therefore, to determine the comparative effect of NTG and SNP on HPV in a rabbit model of isolated lung perfusion with exclusion of the influential factors on HPV. METHODS: In adult white rabbits (n=20), lungs were isolated and perfused with the constant pulmonary blood flow. The acid-base status and temperature of perfusate was also constantly maintained. Thirty minutes later, baseline hypoxic pressor response (HPR) was measured as the difference of pulmonary artery pressure (PAP) between a period of 95% hyperoxic gas inhalation and that of 3% hypoxic gas inhalation. ED50 of NTG and SNP was calculated from the hypoxic pressor response measured in the same way, according to changes of doses (0.5, 1.0, 2.0, and 5.0 microgram/kg). RESULTS: Both NTG and SNP significantly decreased the baseline PAP in the doses of 1.0 microgram/kg and above, and also decreased the HPR in a dose-related manner. ED50 of SNP was significantly lower than that of NTG. CONCLUSIONS: NTG and SNP dilated directly the pulmonary vasculature and inhibited HPV in a dose- related manner. SNP had a greater inhibiting effect on HPV than NTG.

The Effects of Vecuronium and Pancuronium on the Tension of the Isolated Rat Tracheal Smooth Muscle / 대한마취과학회지

BACKGROUND: Non-depolarizing muscle relaxants have their muscle relaxing effect by competing with acetylcholine (ACh) at the nicotinic receptor level. What are the effects of such muscle relaxants on the tracheal smooth muscle? This present study was set up to address the question as to how vecuronium and pancuronium influence the tracheal smooth muscle. METHODS: Sixty male Sprague-Dawley rat tracheal smooth muscles were isolated at optimal length for isometric force. The preparations were set up in an organ bath containing Tyrode's solution. And isometric force displacement transducer and physiograph were used to record the change in force. After the equilibration period the preparations were contracted with ACh 10(-5) M and carbachol 3x10(-7)M seperately. The preparations were washed with fresh tyrode's solution and allowed to return passively to resting tone. Then the cumulartive effect of ACh (from 3 10(-7) M through 10(-5) M) and carbachol (CCh, from 10(-8) M through 3 10(-6) M) were produced before and after pretreating the preparation with vecuronium (10(-5) M and 10(-6) M) and pancuronium (10(-5) M and 10(-6) M) respectively. Also, we studied the changes of contraction produced by neostigmine before and after pretreatment with vecuronium (10(-5) M and 3 10(-5) M) and pancuronium (3 10(-6) M and 3 10(-5) M). RESULTS: Vecuronium shifted the ACh dose-response curve of the tracheal contraction to the left (p0.05). CONCLUSIONS: Vecuronium inhibits the ACh hydrolyzing enzyme, especially acetylcholinesterase. Therefore it potentiates ACh contraction in the tracheal smooth muscle, but not the CCh contraction, while pancuronium has a different effect in comparison with vecuronium. That is, at a low concentration it reveals an antagonistic effect on the muscarinic M2 receptor and at a higher concentration it has an antagonistic effect on the muscarinic M3 receptor in the tracheal smooth muscle.

Effect of Sevoflurane and Isoflurane on Hypoxic Pulmonary Vasoconstriction in the Isolated Rabbit Lung / 대한마취과학회지

BACKGROUND: In vitro and in vivo studies have shown that inhalation anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV). The aim of this study was to investigate the effect of isoflurane and sevoflurane on HPV in the isolated rabbit lungs. METHODS: Isolated constant-flow perfused lungs from New Zealand white rabbit were randomly allocated to treatment with either isoflurane (n=8) or sevoflurane (n=8). HPV, defined as an increase in pulmonary arterial pressure at constant flow, was elicited by decreasing inspiratory oxygen concentration from 95% to 3% for 5 min. This effect was determined without and with increasing concentration of anesthetics (at 0.5, 1.0, and 2.0 MAC of isoflurane, and at 0.6, 0.9, and 1.2 MAC of sevoflurane). The HPV response in the presence of anesthetics was expressed as a percentage of the pressor response in the absence of anesthetics and dose-response relationship were calculated using the nonlinear least-squares method. RESULTS: The percent hypoxic pressor response (%deltaP) of isoflurane were 100%, 78.4%, 45.1%, and 19.6% at 0, 0.5, 1.0, and 2.0 MAC, respectively. The %deltaP of sevoflurane were 100%, 66.6%, 40.0%, and 22.2% at 0, 0.6, 0.9, and 1.2 MAC, respectively. Values (mean+/-SD) for the half-inhibition values (ED50) were 0.90+/-0.14 and 0.81+/-0.15 MAC, and for the slopes were 1.97+/-0.52 and 1.84+/-0.59 for isoflurane and sevoflurane, respectively. There were no statistical difference between the values for ED50 or between the values for slope. CONCLUSIONS: We conclude that sevoflurane and isoflurane inhibit the HPV reponse in a dose-related manner with same potency and slope.

The Effects of Acid-Base Imbalance on the Cisatracurium-Induced Neuromuscular Blockade in the Cat / 대한마취과학회지

BACKGROUND: Cisatracurium is a nondepolarizing muscle relaxant. It less likely release histamine and has better cardiovascular stability. It presumably undergoes pH and temperature- dependent, nonenzymatic chemical process, Hofmann reaction. In vitro studies, Hofmann reaction was enhanced with increasing pH, but, in vivo the influence of acid-base imbalance is not well defined. METHODS: To evaluate the effects of acid-base imbalance on the neuromuscular blockade of cisatracurium in the cat, we induced acid-base imbalance and performed cumulative dose-response studies. RESULTS: ED50 of the cisatracurium was significantly reduced in all groups. Dose-response curves from all acid-base imbalance groups did not have significant differences in slopes. But, all showed shift-to-left when compared with control curve, showing decreased ED50. Duration of action was not affected. Recovery index was significantly changed in respiratory and metabolic alkalosis. CONCLUSIONS: It may be concluded that acid-base imbalance significantly augmented the potency of cisatracurium, but, changes of recovery index in this study may be resulted from systemic instability such as unstable hemodynamic state by the prolonged experiment.