静脉注射美托洛尔、地尔硫卓治疗快速心房纤颤的临床疗效观察

目的:观察美托洛尔注射液和地尔硫卓注射液治疗快速房颤的有效性和安全性。方法:105例符合入选标准的快速房颤患者被随机分为3组,美托洛尔组39例:5mg美托洛尔缓慢静脉注射,观察5min,如无效重复一次,连续用药3次,总量15mg;地尔硫卓35例:地尔硫卓15mg稀释后静脉注射,观察15min,如无效重复1次,继以15mg/h维持。西地兰组31例:西地兰0.2～0.4mg稀释后静脉注射,观察10min,如无效追加0.2～0.4mg,连续用药3次;总量0.6～1.0mg。记录用药前、后心室率和血压变化,并比较在各观察时间点上的有效率。结果:与西地兰相比,美托洛尔和地尔硫卓起效更快[(36.9±11.6)min∶(8.2±4.5)min∶(9.1±3.8)min,P<0.05],心室率下降幅度更明显(25.22%∶33.32%∶37.50%,P<0.05),治疗有效率更高(71.0%∶89.7%∶91.4%,P<0.05)。而美托洛尔组和地尔硫卓组之间无显著性差异。三组均无严重不良反应发生。结论:美托洛尔注射液和地尔硫卓注射液均能快速、安全、有效控制快速房颤的心室率。     

In vitro/in vivo correlation of prolonged release dosage forms containing diltiazem HCl

Six preparations were considered: three multiple unit dosage forms (micropellets in capsules) (D, E and G) and one matrix tablet (B) were experimental prolonged release formulations, two non-disintegrating tablets (A and C) were commercial products. The in vitro dissolution behaviour of the differing formulations was investigated using the USP XXII paddle apparatus. The in vivo study was effected on a panel of 12 healthy volunteers. The two commercial tablets (A and C) showed mean dissolution time (MDT) of 1.34 and 1.44 h and t_d of 91 and 92 min, respectively; for prolonged release formulations (B, E, D, and G) MDT ranged between 2.28 and 4.23 h and t_d between 149 and 291 min. The mean residence time (MRT) was 8.68 and 6.47 h for tablets A and C, respectively; it ranged between 9.62 and 10.24 h for the multiple unit formulations E, D, and G and was 11.27 h for matrix B. Formulation B also showed the higher apparent elimination half-life t_1/2 (7.12 h), while apparent t_1/2 for all the other formulations were very similar, ranging between 5.04 and 5.28 h. High variability between the various formulations was found for C_max and AUC values, and no relationships could be established with the type of formulation. An in vitro/in vivo correlation was found for all the formulations examined on the basis of analogous parameters (MDT and MRT); (r = 0.83, p <0.05). In a few cases the Wagner-Nelson deconvolution method was applied to individual plasma level versus time curves and the corresponding absorption curves were obtained. In these cases the in vitro/in vivo correlation was tested on the basis of the comparison of the in vivo absorption curves with the in vitro dissolution profiles. This was accomplished using the ‘Levy's plot’ (per cent released versus per cent absorbed) approach and provided further support for the correlation found.     

Elevation of carbamazepine plasma levels by diltiazem in rabbits: a potentially important drug interaction

The effect of diltiazem on the plasma level of carbamazepine (CBZ) was investigated in rabbits. The animals were given either CBZ alone or in combination with diltiazem and plasma samples were collected at different time intervals. The concentration of CBZ was detected using an HPLC method. Diltiazem significantly increased the area under the curve (AUC), the maximum plasma concentration (Cmax), and the elimination half-life (t1/2) of CBZ (p less than 0.05). These results suggest that a potentially harmful drug-drug interaction may occur if CBZ and diltiazem are administered concurrently.     

地尔硫卓联合地高辛治疗心力衰竭并慢性快速房颤分析

目的观察地尔硫卓联合小剂量地高辛对心力衰竭并慢性快速房颤患者血压、心室率和心功能的影响。方法 :心功能Ⅱ～Ⅲ级慢性房颤患者 10 6例 ,随机分为二组 ,对照组 5 0例 ,单用地高辛 ,治疗组 5 6例 ,地尔硫卓与地高辛联用 ,其余治疗二组相同 ,7～ 10d为一疗程 ,观察治疗前后血压、心率、左室射血分数 (LVEF)、心输出量 (CO)。结果 :治疗组较对照组心室率明显下降 ,控制满意 ,血压、LVEF及CO变化二组相似。结论 :地尔硫卓联合小剂量地高辛治疗心衰并慢性快速房颤患者心室率较单用地高辛效果更好 ,且较为安全。     

不同血管保存液对人桡动脉血管移植物的抗痉挛作用

目的 研究不同的血管保存液对人离体桡动脉痉挛的缓解与预防能力。方法 非体外循环冠状动脉旁路手术(OPCAB)19例患者,应用“无接触(No Touch)”外科技术获取自体桡动脉,保留未处理的远段0.8～1.5cm。应用血管环灌流技术(Organ Bath)比较不同保存液的抗痉挛作用和预防痉挛作用。结果 血管环灌流实验显示,在对痉挛状态桡动脉的舒张能力方面,PS、VG、DG、NG溶液均可以在10min内100％舒张血管,舒张曲线显示舒张能力依次为VG、DG、NG、PS,但差异无显著性(P>0.05),在预先浸泡处理桡动脉45～60min后,除对照组(Ringer's Solution)外,所有血管保存液均可以有效地预防离体桡动脉的痉挛,各组间差异无显著性(P>0.05)。结论 罂粟碱溶液、VG、DG、NG溶液均有较好的抗血管痉挛作用,单从抗血管痉挛角度考虑可以用作CABG手术中桡动脉的准备液。     

Effects of verapamil,diltiazem and ryosidine on the release of dopamine and acetylcholine in rabbit caudate nucleus slices

Summary Slices of the rabbit caudate nucleus were preincubated with ³H-dopamine or ³H-choline and then superfused with label-free medium. Release of ³H-dopamine and ³H-acetylcholine was elicited by either electrical stimulation at 8 (in one series 2) Hz, or an increase in the K⁺ concentration by 50 mmol/l, or addition of L-glutamate 1 mmol/l. Verapamil 1 mol/l, diltiazem 1 and 10 mol/l, and ryosidine 1 mol/l failed to the reduce the electrically-, K⁺- and glutamate-evoked overflow of tritium. Verapamil 1 mol/l and diltiazem 10 mol/l also failed to reduce the electricallyevoked overflow (2 Hz) when dopamine receptors, neuronal dopamine uptake, and neuronal choline uptake were blocked by domperidone, nomifensine and hemicholinium, respectively. Inhibition of the evoked overflow of tritium was only obtained when concentrations were increased to verapamil 10 mol/l, diltiazem 100 mol/l and ryosidine 10 mol/l. The inhibition was generally small. It was more evident for slices preincubated with ³H-choline than for those preincubated with ³H-dopamine, because in the latter verapamil, diltiazem and (much less) ryosidine accelerated the basal efflux of tritium. The inhibition of the K⁺-evoked overflow of tritium was probably due to blockade of Ca²⁺ channels because this overflow was Ca²⁺-dependent but tetrodotoxin-resistant. In contrast, the inhibition of the electrically- and glutamateevoked overflow possibly involved blockade of Na⁺ channels as well. The results indicate that three calcium antagonists from different chemical classes are very weak inhibitors of Ca²⁺ entry into, and hence transmitter release from, the terminal axons of central dopaminergic and cholinergic neurones. The function of the high affinity calcium antagonist binding sites that have been identified in brain remains unknown.     

地尔硫卓对失血性休克犬肾脏的保护作用

目的：探讨地尔硫卓（Ｄｉｌｔｉａｚｅｍ,Ｄｉｌ）对失血性休克犬肾脏的保护作用及机理。方法：动脉放血,使血压降低至５３３～６６７ｋＰａ（４０～５０ｍｍＨｇ）,维持９０ｍｉｎ后回输血液进行复苏。在休克３０ｍｉｎ时,分别给动物输注盐水和（或）Ｄｉｌ。结果：Ｄｉｌ能明显提高失血性休克动物的平均动脉压（ＭＡＰ）;降低肾脏组织中的丙二醛（ＭＤＡ）含量和超氧化物歧化酶（ＳＯＤ）的活性;保护肾脏组织的超微结构。结论：Ｄｉｌ对失血性休克犬的肾脏具有保护作用。     

Effects of diltiazem,a Ca2+ channel blocker,on naloxone-precipitated changes in dopamine and its metabolites in the brains of opioid-dependent rats

The effects of diltiazem, an L-type Ca²⁺ channel blocker, on naloxone (an opioid receptor antagonist)-precipitated withdrawal signs and changes in extracellular levels of dopamine (DA) and its metabolites in various brain regions of morphine (a -opioid receptor agonist) or butorphanol (a// mixed opioid receptor agonist) dependent rats were investigated using high performance liquid chromatography fitted with an electrochemical detector (HPLC-ED). Rats were rendered opioid-dependent by continuous intracerebroventricular (ICV) infusion with morphine (26 nmol/µl per h) or butorphanol (26 nmol/µ1 per h) for 3 days. The expression of physical dependence produced by these opioids, as evaluated by naloxone (5 mg/kg, IP)-precipitated withdrawal signs, was reduced by concomitant infusion of diltiazem (10 and 100 nmol/µl per h). Under the same condition, naloxone decreased the levels of: DA in the cortex, striatum, and midbrain; 3,4-dihydroxyphenylacetic acid (DOPAC) in the cortex, striatum, limbic areas, and midbrain; and homovanilic acid (HVA) in the striatum, limbic areas, and midbrain regions. In animals rendered dependent on butorphanol, the results obtained were similar to those of morphine-dependent rats except for the changes in DOPAC levels. Furthermore, concomitant infusion of diltiazem and opioids blocked the decreases in levels of DA, DOPAC, and HVA in a dosedependent manner. These results suggest that the augmentation of intracellular Ca²⁺ mediated through L-type Ca²⁺ channels during continuous opioid infusion results in a decrease in extracellular levels of DA and its metabolites in some specific regions, which are intimately involved in the expression of withdrawal syndrome precipitated by naloxone.     

Alteration of loosely bound calcium in the guinea pig organ of Corti after treatment with diltiazem as calcium channel blocker

After oral administration of the organic calcium channel blocker diltiazem to guinea pigs for 7 days, calcium ions were precipitated with potassium antimonate in the cochleae. The spatial distribution of the precipitates was studied by energy-filtering transmission electron microscopy and the amount of the ultrastructural reaction products formed was determined semiquantitatively by an image processing system. Compared with untreated control ears, the number of the formed precipitates was reduced drastically in the inner hair cells after diltiazem treatment. In addition, electron microscopic analysis revealed that the number of calcium precipitates attached at the basolateral membrane of the outer hair cells was clearly reduced when compared with untreated control specimens. A large number of histochemical reaction products could be identified in the basilar membrane and were also observed in the untreated control specimens. The spatial distribution of the calcium precipitates in the lamina reticularis was not affected by diltiazem treatment and calcium precipitates could be identified within different cell membranes. The technique used was considered to be helpful for identifying calcium channels ultrastructurally in intact undissected tissues and to support light microscopic analyses and patch-clamp electrophysiological measurements.