Salbutamol disposition and dynamics in conscious rabbits: Influence of the route of administration and of the dose

This study assessed the influence of dose and route of administration on salbutamol kinetics and hypokaliemic effect. Salbutamol plasma kinetics were studied in a first group of 6 rabbits who received 60, 800, and 60 g/kg by the intravenous (iv), oral (po), and intratracheal (it) routes, respectively, at 1-week intervals. A second group of 6 rabbits received 120, 2400, and 120 g/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 g/kg), total plasma clearance was 82±5 ml/min per kg, apparent volume of distribution was 5.0±0.5 l/kg, and terminal half- life was 41±2 min. Similar values were estimated when 120 g/kg of salbutamol was administered iv or was given po or it. The bioavailability of po and it salbutamol was approximately 1 and 20%, respectively. For the first group, the maximal decrease in plasma potassium elicited by salbutamol was 0.80±0.19, 0.48±0.22, and 0.78±0.46 mmol/l, and for the second group, maximal decrement was 1.31±0.37, 0.70±0.24, and 0.84±0.17 mmol/l for the iv, po, and it routes, respectively. Compared to salbutamol peak plasma concentrations, maximal decrease in plasma potassium appeared between 60 and 108 min later for the iv route, 90 and 25 min later for po and it routes, and for this reason, the hypokaliemic effect was not associated to salbutamol plasma concentrations. The hypokaliemic effect was dependent upon the route, e.g., po>it>iv. It is concluded that (i) salbutamol plasma kinetics are first-order independently of the route of administration, and (ii) salbutamol hypokaliemic effect is modulated by the dose and the route of administration.List of abbreviations AUC Area under salbutamol plasma concentration-time curve - cl_INT Salbutamol intrinsic clearance - cl_T Salbutamol total plasma clearance - c_MAX Salbutamol maximal plasma concentration - F Fraction of the dose of salbutamol reaching the systemic circulation - iv Intravenous route of administration - it Intratracheal route of administration - po Oral route of administration - V_area Salbutamol apparent volume of distribution - T ₂ ¹ Salbutamol half-life of the terminal phase - t_MAX Time to observe the maximal decrease in plasma potassium - e_MAX Predicted maximal effect of salbutamol - EC₅₀ Concentration of salbutamol eliciting 50% of e_MAX Supported by the Medical Research Council of Canada (MT-10874). Sylvie Perreault is recipient of a Bourse Formation de troisième cycle des Fonds de la Recherche en Santé du Québec.     

The rotational component in the dynamics of the C2–3 spinal segment

Summary The technique of the PA axial projection of the arches of the upper cervical vertebrae into the occipital foramen and the normal findings, are described. The influence of maximum forced anteflexion at the craniocervical junction and rotation of the head on the relations of atlas and axis is demonstrated. It seems that in this position rotation at atlasaxis level is restricted and partly transmitted to the C_2–3 segment. Thus, selective clinical examination of the rotational component of the dynamics at C_2–3 can be achieved and the pathological restrictions of movement can be assessed.     

Monoamine acid metabolites in ventricular CSF of patients with brain tumours

Summary Homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) in ventricular CSF were determined in 19 patients (12 female 7 male) with brain tumours. No relationship was found between ventricular fluid pressure (VFP) and levels of HVA and 5-HIAA. A relationship was observed between ventricular CSF, HVA concentrations and tumour induced alterations in CSF dynamics. HVA concentrations were very high in patients whose tumours involved the third ventricle, the aqueduct, or the fourth ventricle, producing marked alterations in CSF flow. HVA concentrations significantly lower than in controls were observed in cases where tumours involved the lateral ventricles. Concentrations of acid metabolites in patients with little or no alteration in CSF dynamics corresponded with those in patients with other neurosurgical disorders.     

Correlation dimension of the human sleep electroencephalogram

Sleep electroencephalogram (EEG) was analyzed by nonlinear analysis. Polysomnography of a healthy male subject was analyzed and the correlation dimension was calculated. The mean correlation dimensions decreased from stage 'awake' to stages 1, 2 and 3, and increased during rapid eye movement (REM) sleep. These results were also seen at every sleep cycle. During each sleep cycle the correlation dimensions decreased for slow wave sleep, then increased for REM sleep. The mean correlation dimension of the sleep EEG in the second half of the night was significantly higher than those in the first half of the night. A significant change was seen both during REM sleep as well as in sleep stage 2. Nonlinear analysis may be a useful method in the analysis of the entire sleep electroencephalogram.     

纳洛酮治疗脑梗死的疗效观察

目的　观察纳洛酮治疗脑梗死的疗效。方法　将 2 6 0例脑梗死患者随机分组 ,治疗组 12 8例 ,予纳洛酮治疗 ;对照组 132例 ,予一般治疗 ,观察神经功能缺损变化及血液流变学变化。结果　治疗组较对照组神经功能改善和血液流变学改变有显著性差异。结论　纳洛酮具有抗凝作用 ,对脑梗死患者神经功能恢复有较好疗效。     

Computational flow study of the continuous flow ventricular assist device, prototype number 3 blood pump

A computational fluid dynamics study of blood flow in the continuous flow ventricular assist device, Prototype No. 3 (CFVAD3), which consists of a 4 blade shrouded impeller fully supported in magnetic bearings, was performed. This study focused on the regions within the pump where return flow occurs to the pump inlet, and where potentially damaging shear stresses and flow stagnation might occur: the impeller blade passages and the narrow gap clearance regions between the impeller-rotor and pump housing. Two separate geometry models define the spacing between the pump housing and the impeller's hub and shroud, and a third geometry model defines the pump's impeller and curved blades. The flow fields in these regions were calculated for various operating conditions of the pump. Pump performance curves were calculated, which compare well with experimentally obtained data. For all pump operating conditions, the flow rates within the gap regions were predicted to be toward the inlet of the pump, thus recirculating a portion of the impeller flow. Two smaller gap clearance regions were numerically examined to reduce the recirculation and to improve pump efficiency. The computational and geometry models will be used in future studies of a smaller pump to determine increased pump efficiency and the risk of hemolysis due to shear stress, and to insure the washing of blood through the clearance regions to prevent thrombosis.     

战术药材储备的系统动力学研究

探讨战术药材储备系统模型的动力生质和行为方法：应用系统动力学方法和构建战术药材储备模型,借助于计算机编程,模拟有关参数变化时的系统行为。结果：初始储备量的大小对系统的平均库存量和平均缺货量无明显影响;目标储备量,到货速率和发化速度对平均存量和平均缺货量有显著影响。结论在有效控制到化速率的情况下,降低战术药材储备量对系统的保障效能无不利影响。     

血虚证与补血药白芍辨证药物动力学关系研究

目的:通过对补血药白芍主要效应成分芍药苷在血虚证和健康小鼠体内血药浓度比较,探讨血虚证与补血药的辨证药物动力学关系。方法:建立血虚证动物模型,将实验动物分为空白对照组,对照组(健康小鼠),实验组(血虚证动物模型),对照组和实验组均给予白芍提取物灌胃。采用高效液相色谱技术,比较两组小鼠灌胃后不同时间点血浆中芍药苷浓度的差异。结果:实验组小鼠平均血药浓度在60 min、90 min时明显高于对照组,实验组小鼠血浆中芍药苷平均血药浓度为116．52±5．28 ng/μl,而对照组为41．49±2．86 ng/μl,二者比较有显著差异(p<0．001)。结论:血虚证小鼠血浆中芍药苷浓度较健康小鼠高,说明血虚证与补血药白芍存在辨证药物动力学关系。     

EGF刺激下PIP2水解的数学模型

为了研究表皮生长因子刺激下细胞膜上磷脂酰肌醇二磷酸水解的动力学特性,我们根据质量作用定律和准稳态近似原则建立数学模型,模拟磷脂酰肌醇二磷酸的代谢;建立了磷脂酰肌醇二磷酸和表皮生长因子受体间浓度关系的微分方程,讨论了各个参数对磷脂酰肌醇二磷酸浓度变化趋势的影响。这个数学模型描述了磷脂酰肌醇二磷酸代谢的生物学特性以及关键信号分子间的浓度依赖关系。     

原发性开角型青光眼眼部血流动力学以及高血压对其的影响

目的　探讨原发性开角型青光眼眼部血流动力学以及高血压对其的影响。方法　研究对象为我院确诊的原发性开角型青光眼患者 4 9例 4 9眼 ,其中 19例有全身高血压病史。根据是否合并高血压分为 2组 ,应用彩色多普勒成像技术检测眼动脉 (OA)、视网膜中央动脉 (CRA)和后短睫状动脉 (SPCA)的血流动力学指标 ,取年龄相匹配的正常人 18例作为对照组。结果　青光眼患者的CRA及SPCA的收缩期峰值流速 (PSV) ,分别为 (7.6 4cm·s-1± 2 .6 0cm·s-1,9 2 1cm·s-1± 1.16cm·s-1)、舒张期血流速度 (EDV )(2 .0 4cm·s-1± 0 .95cm·s-1,2 .98cm·s-1± 0 .88cm·s-1)及平均流速 (MV) (3.87cm·s-1± 1 34cm·s-1,4 92cm·s-1±1 12cm·s-1)均低于正常对照组 ,阻力指数 (RI) (均为 0 70±0 0 6 )明显高于正常对照组。合并高血压的青光眼患者CRA及SPCA的PSV(9 4 5cm·s-1± 2 38cm·s-1,10 2 3cm·s-1±1 2 5cm·s-1)、EDV(3 0 8cm·s-1± 1 12cm·s-1,3 5 2cm·s-1± 1 10cm·s-1)和MV (4 92cm·s-1± 1 5 2cm·s-1,5 5 4cm·s-1± 1 2 6cm·s-1)明显高于非高血压的青光眼患者。结论　青光眼患者的球后血管的血流速度明显下降 ;无高血压的青光眼患者的血流速度低于合并全身高血压的青光眼患者。