Intradermal Histamine Release by 3 Muscle Relaxants

The induration and redness caused by intradermal injections of equipotent doses of atracurium, vecuronium and d-tubocurarine were measured in six healthy, male volunteers. Atracurium and d-tubocurarine were almost indistinguishable in their reactions. Vecuronium caused a significantly smaller response than both atracurium and d-tubocurarine. We therefore suggest that of these three drugs, vecuronium may cause the least histamine release and is, perhaps, the drug of choice in patients with a history of asthma or allergy.     

Five Non-Depolarizing Muscle Relaxants in Precurarization

Five different non-depolarizing muscle relaxants and a control solution of saline were studied as precurarization agents. Two hundred and twenty-two surgical patients (ASA I-II) were allocated in a double-blind fashion to one of the following groups: d-tubocurarine 0.05 mg/kg, alcuronium 0.03 mg/kg, pancuronium 0.01 mg/kg, gallamine 0.25 mg/kg, ORG NC-45 (vecuronium) 0.01 mg/kg and saline solution 0.005 ml/kg. Pretreatment was performed 4 min before administering a 1.5 mg/kg bolus of succinylcholine (SCh). Fasciculations, intubation conditions, duration of neuromuscular blockade after SCh, serum potassium changes and postoperative myalgias (in 60 patients) were recorded. All the drugs studied prevented fasciculations significantly (P less than 0.05) more than in the control group. d-Tubocurarine and alcuronium were superior to the others in this respect. Intubation conditions were best in the control and pancuronium groups, but there was no significant difference between the pancuronium and d-tubocurarine or between the d-tubocurarine and alcuronium groups. Pancuronium pretreatment prolonged the SCh block significantly, whereas other agents shortened the duration of the SCh block. The antagonism of the SCh block apparently also affected intubation conditions, although intubation remained satisfactory. A statistically significant rise in serum potassium level was measured only in the control and pancuronium groups. In the control and pancuronium groups, four patients out of 10 had postoperative myalgias, whereas in the other groups only one or none out of 10 had them (0/10 vs. 4/10; 0.10 greater than P greater than 0.05). In conclusion, d-tubocurarine and alcuronium seem to have advantages over pancuronium, ORG NC-45 and gallamine for precurarization.     

肌松药在肝移植围术期的应用

终末期肝病导致全身脏器受累,使肌肉松弛药药代和药效方面发生复杂改变。肝移植病人应用肌松药,除了要考虑减少肝脏负担外,尚需注意神经肌肉阻滞恢复的困难。以主要经肝脏清除的非去极化肌松药的药效学来评价移植肝功能的早期恢复值得研究。     

肌松药的黄金时代结束了？!

肌松药是现代全麻的重要组成成分，对几乎所有麻醉医生来观是“必不可少”的药物。似乎，它为麻醉医生提供了“安全舒适”的麻醉条件，但不见得其必然为外科医生带来更优越的手术条件，同时也肯定为手术患者带来隐患。不用肌松药实施全麻是天方夜谭吗？常规需要永远延续下去？打破常规的利弊如何权衡？     

Muscle Activation during Push-Ups with Different Suspension Training Systems

The purpose of this study was to analyze upper extremity and core muscle activation when performing push-ups with different suspension devices. Young fit male university students (n = 29) performed 3 push-ups each with 4 different suspension systems. Push-up speed was controlled using a metronome and testing order was randomized. Average amplitude of the electromyographic root mean square of Triceps Brachii, Upper Trapezius, Anterior Deltoid, Clavicular Pectoralis, Rectus Abdominis, Rectus Femoris, and Lumbar Erector Spinae was recorded. Electromyographic signals were normalized to the maximum voluntary isometric contraction (MVIC). Electromyographic data were analyzed with repeated-measures analysis of variance with a Bonferroni post hoc. Based upon global arithmetic mean of all muscles analyzed, the suspended push-up with a pulley system provided the greatest activity (37.76% of MVIC; p < 0.001). Individually, the suspended push-up with a pulley system also provided the greatest triceps brachii, upper trapezius, rectus femoris and erector lumbar spinae muscle activation. In contrast, more stable conditions seem more appropriate for pectoralis major and anterior deltoid muscles. Independent of the type of design, all suspension systems were especially effective training tools for reaching high levels of rectus abdominis activation.

Key Points

• Compared with standard push-ups on the floor, suspended push-ups increase core muscle activation.
• A one-anchor system with a pulley is the best option to increase TRICEP, TRAPS, LUMB and FEM muscle activity.
• More stable conditions such as the standard push-up or a parallel band system provide greater increases in DELT and PEC muscle activation.
• A suspended push-up is an effective method to achieve high muscle activity levels in the ABS.

Key words: EMG, unstable, core, trunk, exercise     

Mast Cell Density and Subtypes in the Skin of Shar Pei Dogs with Cutaneous Mucinosis

Skin biopsies from 13 Shar Peis showing signs of cutaneous mucinosis and 13 control dogs of different breeds with no clinical or histological evidence of skin disease were examined. One section of each tissue sample was stained with haematoxylin and eosin, and another with toluidine blue to demonstrate the sulphated acid glycosaminoglycans in mast cell (MC) granules. To investigate the MC subtypes involved, the tryptase and chymase content of mast cells was evaluated by a double enzyme-immunohistochemical staining technique. Regardless of the staining technique, a significantly lower mast cell density in the skin of Shar Peis was demonstrated. In the dermis of control dogs, we detected a median mast cell density of 31.2 MC/mm² using the toluidine blue staining method and 27.5 MC/mm² using the double labelling technique. In Shar Peis only 9.1 MC/mm² were found by toluidine blue staining (P = 0.001) and 14.8 MC/mm² by the double labelling method (P = 0.0387). The percentile distribution of mast cell subtypes was also significantly different in Shar Peis as compared to control dogs. Whereas in the dermis of control dogs the predominant mast cell subtype was the tryptase and chymase containing MC (TC-MC) (60.4 %), in Shar Pei skin the only chymase containing MC (C-MC) predominated (62.2 %) and the percentage of TC-MC was significantly lower (32.9 %P = 0.0016). The percentage of only tryptase containing MC (T-MC) (4.7 %) was higher in Shar Peis compared to control dogs (1.9 %P = 0.0178). The data obtained indicate a possible involvement of mast cell subtypes in the pathogenesis of cutaneous mucinosis. Further investigations on the pathophysiological role of mast cell subtypes may foster understanding of the pathogenesis of cutaneous mucinosis.     

The Pulmonary First-pass Uptake of Five Nondepolarizing Muscle Relaxants in the Pig

Background: It is not known whether the lungs influence the early pharmacokinetics of muscle relaxants and, if they do, whether differences in pulmonary uptake contribute to the differences in potency and/or onset time among muscle relaxants. Because the lungs are uniquely positioned, receive the entire cardiac output, have a large capillary surface area, and can temporarily store various basic drugs, the authors determined whether substantial pulmonary first-pass uptake of muscle relaxants occurs.

Methods: In 14 pigs, rocuronium, vecuronium, Org 9487, Org 7617, or d-tubocurarine were administered simultaneously with indocyanin green within 1 s into the right ventricle, and then arterial blood was sampled every 1.2 s (in the first min). The tibialis muscle response was registered mechanomyographically.

Results: The maximum block was 93% (68-100% [median and range]). Onset times ranged from 83 s (78-86 s) for rocuronium to 182 s (172-192 s) for d-tubocurarine. Fraction-versus-time outflow curves showed that the peak of muscle relaxants and indocyanin green occurred almost simultaneously. Pulmonary first-pass retention was negligible. The retention of muscle relaxants at 95% passage of indocyanin green was -9% (-31 to 18%). The difference in the mean transit time between muscle relaxant and indocyanin green was 1.0 (0.8 to 1.4), 0.2 (-0.8 to 0.3), 0.3 (0.2 to 0.4), 0.5 (0.2 to 1.3), and -2.2 s for rocuronium, vecuronium, Org 9487, Org 7617, and d-tubocurarine, respectively.     

干细胞生长因子在自体移植中厚皮片中的表达

目的检测干细胞因子（Stem cell factor，SCF）在人自体移植中厚皮片中的表达，初步认识干细胞因子在自体移植皮片色素沉着发生机制中的作用。方法取面颈部自体中厚皮片移植术后1年左右的色素沉着皮片，以自身正常皮肤作为对照，组成配对资料（n=16），利用S—P免疫组化方法，检测SCF在受区移植皮片、受区周围与供区周围正常皮肤的表达与分布，使用MIQAS医学图像定量分析系统，定量检测各组标本中SCF阳性表达面积（PA）、阳性表达强度（OD），计算出阳性表达指数（PI，PI=PA×OD），并就PI值行统计学分析。结果SCF表达定位于表皮基底层的黑素细胞与角朊细胞的胞浆及胞膜表面。SCF在受区移植皮片、受区周围及原供区周围正常皮肤中的PI值分别为158830±53753、86839±21381、85033±16972。SCF在受区移植皮片组的表达与两正常对照组相比具有显著性差异（p〈0．01）；SCF在受区周围正常对照皮肤与原供区周围正常皮肤中的表达无差异。结论SCF在自体中厚移植皮片中的表达较在自体正常对照皮肤中显著增高，推测SCF在自体移植皮片色素过度沉着中可能起重要调控作用。     

Hemodynamic Effects in Acute Cardiomyoplasty of Different Wrapped Muscle Activation Times as Measured by Pressure-Volume Relations

A bstract Background : Correct timing of mechanical interaction between wrapped latissimus dorsi muscle (LDM) and the heart during cardiac systole has been poorly understood and remains a controversial issue. Therefore, left ventricular pressure-volume relations were analyzed in acute cardiomyoplasty while changing the synchronization delays. Methods : Effects of different delays between the sensed cardiac R wave and wrapped muscle contraction were studied in goats submitted to acute left cardiomyoplasty. Conductance and micromanometer catheters were used to evaluate hemodynamics. Systolic contribution of the wrapped muscle was studied in preassisted and assisted beats, whereas diastolic effects were studied in assisted and postassisted beats. Results : At best settings, cardiomyoplasty resulted in a significant (p < 0.05) increase in left ventricular ejection fraction (from 42.2 ± 9.2 to 56.7%± 13%), in stroke work (from 2769 ± 1140 to 4271 ± 1717 gm/m²), in dP/dt (from 1185 ± 342 to 1510 ± 285 mmHg/sec), in end-systolic pressure (from 93.5 ± 22.5 mmHg to 97.3 ± 22.3 mmHg), and in peak ejection rate (from 282 ± 64 to 533 ± 241 mL/sec). Stroke volume showed a mean increase of 35% (from 42.2 ± 9.9 mL to 56.9 ± 20.1 mL) during assisted beats. Diastolic function was not substantially impaired at optimal stimulation delay. Incorrect timing of LD contraction resulted in suboptimal improvement or no change in comparison with unassisted hemodynamics. Conclusions : Our study documents support of cardiac performance by LDM. Incorrect timing of heart/wrapped muscle interaction led to suboptimal hemodynamic results. Muscle contraction timing is an important factor in cardiomyoplasty outcome.     

Pharmacodynamic Modeling of Muscle Relaxants: Effect of Design Issues on Results

Background: Pharmacodynamic studies of muscle relaxants use different dosing regimens (such as administration by bolus vs. infusion and doses that produce complete vs. incomplete paralysis). The authors used published data to evaluate the effect of modeling assumptions on pharmacodynamic estimates.

Methods: The authors used a pharmacokinetic-pharmacodynamic dataset in which patients received cisatracurium, 75 or 300 [mu]g/kg (1.5 or 6 x ED95), to generate plasma concentration (Cp) and twitch depression (effect) curves. They then evaluated the impact of the following: assuming that Cp decreased monotonically versus increasing initially before decreasing monotonically; misrecording effect data by 6 s or less; and doses targeting incomplete versus complete paralysis. Parameters evaluated were the steady state Cp depressing twitch tension 50% (C50) and the rate constant for equilibration between plasma and effect site concentrations (ke0).

Results: With the large dose, increasing the time at which Cp peaked from 0.0 to 1.5 min decreased C50 and increased ke0 markedly; with the small dose, changes in both were small. Misrecording the timing of effect had a larger impact with the large dose compared with the small dose. Doses smaller than ED50 or those producing prolonged, complete twitch depression yielded biased and variable estimates.     

Are Plasma Concentration Values Necessary for Pharmacodynamic Modeling of Muscle Relaxants?

Background: The traditional approach to pharmacokinetic/pharmacodynamic modeling of muscle relaxants requires sampling of plasma to determine drug concentrations. The authors recently proposed that certain pharmacodynamic characteristics (IR50, the steady-state infusion rate to maintain 50% twitch depression; keo, the rate constant for equilibration between plasma concentration and effect; and gamma, the Hill factor describing sigmoidicity of the concentration-effect relation) could be estimated without plasma concentration data. Here estimates for IR50, keo, and gamma determined with and without plasma concentration data are compared.

Methods: Six volunteers were given 15-60 micro gram/kg vecuronium on each of two occasions during anesthesia with propofol. Mechanical responses to train-of-four stimulation were measured at the adductor pollicis and at the laryngeal adductors. Various pharmacokinetic models accounting for the presence and potency of vecuronium's 3-desacetyl metabolite and a sigmoid e-max pharmacodynamic model were fit to the resulting plasma concentration and effect (adductor pollicis and laryngeal adductors) data to determine IR50 keo, and gamma for each effect. One model related dose to effect without plasma concentration data.

Results: Values for IR50 (adductor pollicis), IR50 (laryngeal adductors), gamma (adductor pollicis), and gamma (laryngeal adductors) were similar when determined with and without plasma concentration values. Values for keo (adductor pollicis) and keo (laryngeal adductors) were larger when determined without plasma concentration values compared with those determined with these values; however, the ratio of keo (adductor pollicis) to keo (laryngeal adductors) was similar when determined with and without plasma concentration values.     

非去极化肌松药对血组胺,儿茶酚胺浓度的影响

观察２４例拟行心脏手术的成年患者使用潘可罗宁、卡肌宁和万可罗宁后血组胺、儿茶酚胺浓度及心率、血压的变化。结果：潘可罗宁组去甲肾上腺素略有升高，心率、血压则升高明显。卡肌宁组组胺浓度增加显著，同期心率增快、血压下降，组胺的升高同血压的下降呈现负相关，万可罗宁组组胺、儿茶酚胺变化不大，且心率、血压保持平稳。     

Phagocytosis of Different Particulate Dermal Filler Substances by Human Macrophages and Skin Cells

BACKGROUND: Foreign substances have been introduced into the human body with varying degrees of success. Polymethylmethacrylate (PMMA) microspheres of different sizes recently have been manufactured for use as a filler substances in the skin and other organs. OBJECTIVE: To establish whether the size of PMMA microspheres determines whether various cell types initiate phagocytosis. METHODS: The capacity of three different cell lines-U-937 cells, XS 106 and XS 52 Langerhans cells, and HaCaT keratinocytes-to phagocytose microspheres of varying sizes was examined using light and confocal microscopy as well as fluorescence-activated cell sorter (FACS) analysis. Tumor necrosis factor (TNF)-alpha secretion was also determined. RESULTS: The U-937 cells, keratinocytes, and Langerhans cells could phagocytose PMMA particles of 20 microm or smaller. Microspheres larger than 20 microm were not ingested by any of the cells. CONCLUSION: Microspheres larger than 20 microm have a lower likelihood of being phagocytosed. Thus this study suggests that microspheres 40-50 microm in diameter are less likely to initiate an inflammatory reaction when injected into the dermis and subdermis as a filler substance. On the other hand, microparticles made of silicone and polymethacrylate were phagocytosed, possibly because of their different structure.     

全凭静脉麻醉中雷米芬太尼减少肌松药用量的机制探讨

目的：雷米芬太尼作为一种新型的麻醉性镇痛药在临床已经广泛应用于静脉全麻．目前发现在静脉全麻中雷米芬太尼可以明显减少肌肉松弛药的用量．这是否是雷米芬太尼与肌松药的协同作用还不清楚．本研究应用Organon-TOF—WATCH SX肌松监测仪观察垒凭静脉麻醉下腹腔镜手术中靶控输注不同剂量的雷米芬太尼对肌松药罗库溴铵的起效．作用和恢复时间的影响,以此来判断雷米芬太尼与肌松药之间是否有协同作用。方法：选择ASAI—II级．年龄25-55岁,妇科及普外科腹腔镜择期手术病人75例随机分为兰组,全麻诱导：咪唑安定0．04mg·kg^-1,丙泊酚TCI血药浓度3ug·ml^-1．罗库溴铵0．6mg·kg^-1．麻醉维持：A组单纯用TCl丙泊酚．B组用TCl丙泊酚加上TCI雷米芬太尼效应室浓度2ng．mr．．C组用TCI丙泊酚加上雷米芬太尼效应室浓度5ng．mI～,三组异丙酚TCI效应室浓度维持在3ug·ml^-1。左右,根据病人的反应调整．将麻醉深度控制在满足手术需要和术中BIS在40-60之间．用Organon—TOF—WATCH SX肌松监测仪记录罗库溴铵（0．6mg·kg^-1）的起效时间（从给药至TOF比值下降到25％的时间）、维持时间（从TOF值低于25％至恢复到25％）、恢复时间（从TOF比值恢复到25％至TOF比值恢复到75％）用美国Aspect公司的BIS-XP监测仪控制麻醉深度。结果：罗库溴铵的起效时间三组分别为0．96±0．35min．1．12±0．51min。1．11±0．34min,三组之间无统计学差异（P〉0．05）;罗库溴铵的作用时间三组分别为39．94±10．17min．42．45±11．07min。42．46±11．25min,备组间没有统计学差异（P〉0．05）．罗库溴铵的·I灰复时间三组分别为11．68±4．99min．13．44±5．93min．12．20±2．61min．各组间没有统计学差异（P〉0．05）。结论：不同TCI效应室浓度的雷米芬太尼没有明显延长单次注射罗库溴铵（0．6mg·kg^-1）的起效．作用和恢复时间．提示雷米芬太尼减少静脉全麻中肌松药用量的作用机制是中枢性的。     

Effects of Muscle Relaxants on Mask Ventilation in Anesthetized Persons with Normal Upper Airway Anatomy

BACKGROUND:: Recent studies suggest advantages of muscle relaxants for facemask ventilation. However, direct effects of muscle relaxants on mask ventilation remain unclear because these studies did not control mechanical factors influencing ventilation. We tested a hypothesis that muscle relaxants, either rocuronium or succinylcholine, improve mask ventilation. METHODS:: In anesthetized adult persons with normal upper airway anatomy, tidal volumes during facemask ventilation were measured while maintaining the neutral head and mandible positions and the airway pressures of a ventilator before and during muscle paralysis induced by either rocuronium (n = 14) or succinylcholine (n = 17). Tidal volumes of oral and nasal airway routes were separately measured with a custom-made oronasal portioning full facemask. Behavior of the oral airway was observed by an endoscope in six additional subjects receiving succinylcholine. RESULTS:: Total, oral, and nasal tidal volumes did not significantly change at complete muscle paralysis with rocuronium. In contrast, succinylcholine significantly increased total tidal volumes at 60 s after its administration (mean ± SD; 4.2 ± 2.1 vs. 5.4 ± 2.6 ml/kg, P = 0.02) because of increases of ventilation through both airway routes. Abrupt tidal volume increase occurred more through oral airway route than nasal route. Dilation of the space at the isthmus of the fauces was endoscopically observed during pharyngeal fasciculation in all six subjects. CONCLUSIONS:: Rocuronium did not deteriorate facemask ventilation, and it was improved after succinylcholine administration in association with airway dilation during pharyngeal fasciculation. This effect continued to a lesser degree after resolution of the fasciculation.