地尔硫(艹卓)对自发性高血压大鼠左心室舒张功能的影响及其可能机制

目的:观察地尔硫(艹卓)对自发性高血压大鼠(SHR)左心室舒张功能的影响,并探讨这种影响是否与肌浆网钙ATP酶(SERCA2)蛋白的表达、活性及心肌纤维化相关. 方法:将22只12周龄SHR随机分为地尔硫(艹卓)组(25 mg·kg-1·d-1,SHR-D),苯那普利组(10 mg·kg-1·d-1,SHR-B)和SHR空白对照组(蒸馏水灌胃,SHR-C);另设WKY大鼠7只为正常对照组(WKY).灌胃法给药18周后测定左心室心功能,计算左心室/体重比(LVW/BW),Western印迹杂交测定左心室心肌SERCA2的表达,无机磷比色法检测心肌肌浆网Ca2 ATPase活性.饱和苦味酸天狼星红染色分析胶原容积分数(CVF)和血管周围胶原面积(PVCA),估计心肌纤维化程度. 结果:SHR-D组和SHR-B组的LVEDP显著低于SHR-C组,SHR-D组和SHR-B组之间差异无统计学意义(P＞0.05).与SHR-C组相比,SHR-D组与SHR-B组的-dp/dtmax/MAP增加.地尔硫(艹卓)和苯那普利治疗明显增加SERCA2蛋白的表达(SHR-D:0.38±0.07,SHR-B:0.42±0.06,SHR-C:0.47±0.07)与活性(SHR-D:8.2±0.07,SHR-B:10.5±1.95,SHR-C:6.3±0.75).SHR-D组左心室内膜及心肌小动脉周围的胶原减少,其作用类似于SHR-B组. 结论:地尔硫(艹卓)可改善SHR左心室舒张功能,其机制可能与增加SERCA2蛋白的表达及活性,抑制心肌纤维化有关.     

静脉地尔硫(卓)治疗老年人快速心室率房颤、房扑和室上速的临床观察

目的　观察静脉地尔硫艹卓 对老年人快速心室率的房颤、房扑及室上速的疗效与安全性。方法　 1 5例患者 (7例房颤、3例房扑、5例室上速 )静脉注射地尔硫艹卓 1 0～ 1 5mg,有反应者继以 1 0～ 1 5mg/ h浓度持续静点 6～ 1 2 h。结果　用药后心室率比用药前基础心率减少 >2 0 % ;转复为窦性心律或心室率 <1 0 0次 / min为治疗有反应 ,本组 1 5例患者 1 2例 (80 % )有反应 ;用药后心室率下降最大效应时间 1 1 min,心室率下降幅度 42± 1 6次 / min。结论　地尔硫艹卓 能安全地应用于快速心室率的房颤或房扑及室上速的老年人 ,并在大多数病人能迅速有效地达到心率的控制和中止室上速的发作 ,而且不会引起或加重心功能障碍。     

静脉应用地尔硫(艹卓)治疗心房纤颤伴快速心室率疗效观察

目的　观察静脉应用地尔硫艹卓对减慢心房纤颤伴快速心室率患者心室率的疗效及其安全性。方法　４０ 例心房纤颤伴快速心室率者被随机分为地尔硫艹卓治疗组和毛花甙丙治疗组,观察用药后心室率和血压变化。结果　毛花甙丙组有效率为７５ ％ ,地尔硫艹卓组为９５ ％ , Ｐ＜ ００１ 。毛花甙丙组最大效应时间为９６０ ±２８０ 分钟,地尔硫艹卓组为８０ ±２５ 分钟。地尔硫艹卓组有５ 例病人出现一过性无症状性低血压,无需处理。结论　地尔硫艹卓对降低心房纤颤伴快速心室率患者的心室率具有疗效高、起效迅速、安全等优点。     

曲美他嗪联合地尔硫卓治疗心绞痛的疗效研究

目的 研究曲美他嗪联合地尔硫卓治疗心绞痛的效果.方法 80例心绞痛患者,随机分为观察组与对照组,每组40例.两组患者均接受常规治疗,对照组采取曲美他嗪治疗,观察组采取曲美他嗪联合地尔硫卓治疗.比较两组治疗效果,心绞痛发作次数、发作时间,不良反应发生情况.结果 观察组的总有效率95.00％ 高于对照组的77.50％,差异...     

Effects of diltiazem,a calcium antagonist,on regional myocardial function and mitochondria after brief coronary occlusion

The purpose of the study was to assess the effect of the calcium antagonist diltiazem on mechanical and mitochondrial function of ischemic myocardium of the dog.Persistent depression of developed tension following brief coronary occlusion was measured in anesthetized and thoracotomized dogs. The extent of persistent depression of developed tension during reperfusion depended on the duration of occlusion and also on the pressure-rate index during occlusion.Diltiazem prevented the marked drop in developed tension of the ischemic segment of the myocardium following 5 min or 10 min of coronary occlusion. The inactive optical isomer of diltiazem had no effect on developed tension before or after coronary occlusion. Depression of the state 3 rate of respiration of mitochondria observed following 10 min of occlusion of coronary artery was almost completely reversed by pretreatment with diltiazem.Diltiazem may reduce the damage of ischemic myocardium during occlusion by hemodynamic action of the drug, and possibly by preventing damage to mitochondria.     

Preventive effects of diltiazem on cyclosporin A-induced vascular smooth muscle dysfunction

Cyclosporin A may cause vascular smooth muscle dysfunction due to calcium overload as a consequence of chronically augmented calcium influx. In the present study, the responsiveness to vasoconstrictors was investigated in rats after chronic treatment for 6 weeks with placebo, cyclosporin A (30 mg/kg per day), diltiazem (60 mg/kg per day), or cyclosporin A plus diltiazem. Twenty-four hours after the last oral treatment the animals were sacrified and rings of the thoracic aorta were suspended in organ chambers under isometric conditions in the absence of cyclosporin A or diltiazem. Chronic treatment with cyclosporin A significantly augmented contractions to angiotensin II (10^-9–10^-5 M). This effect was prevented by cotreatment with diltiazem. Diltiazem did not affect the cyclosporin A-induced reduction in the response to potassium chloride (10–80 mM). The contractions to phenylephrine (10^-9–10^-6 M) and endothelin-1 (10^-9–10^-7 M) were not significantly different in the four groups. The preventive effect of diltiazem against the cyclosporin A-induced hypersensitivity to angiotensin II supports the hypothesis of increased calcium influx during cyclosporin A therapy. The results may provide an additional rationale for the use of calcium antagonists in the treatment of the vascular side effects of cyclosporin A.     

Diltiazem alters some withdrawal signs in pentobarbital-dependent rats

Male, Sprague-Dawley rats were made dependent on pentobarbital sodium (PB) by continuous, IP infusion of PB for 13 days. On Day 14, a 72-hour PB-free period began during which body weight, 24-hour water consumption and withdrawal scores were noted. In Study 1, rats were placed into one of four treatment groups at the start of the PB-free period. Groups included saline-infused control rats with twice daily administration of either vehicle or diltiazem and PB-dependent rats treated twice daily with either diltiazem or vehicle. In Study 2, rats were placed into one of the four treatment groups at the start of the 13-day PB-infusion period. In Study 1, PB-dependent rats treated with diltiazem exhibited approximately 10% loss of body weight at both 12 and 48 hours of the PB-free period while PB-dependent rats treated with vehicle exhibited only about a 5% loss of body weight. PB-dependent rats treated with either diltiazem or vehicle both exhibited about a 40% decline in water consumption and were noted to have significant increases in withdrawal scores by the fifth hour of the PB-free period. As compared to the scores of PB-dependent rats treated with vehicle, diltiazem did not significantly alter the withdrawal scores of PB-dependent rats at any time point during the PB-free period. In Study 2, the chronic administration of diltiazem to PB-infused rats produced both a significant decrease in water consumption at 48 and 72 hours and a significant increase in withdrawal scores from 3–48 hours. Mortality, which occurred only during the PB-free period and involved only PB-dependent rats treated with diltiazem, reached 50% by the end of the PB-free period. It appears that the chronic administration of diltiazem for 13 days led to an exacerbation of some of the typical withdrawal symptoms in PB-dependent rats.     

Antiischemic effect of intracoronary diltiazem on myocardial ischemia during PTCA

Summary To evaluate the effect of intracoronary diltiazem on myocardial ischemia during percutaneous transluminal coronary angioplasty (PTCA), 38 patients were randomly assigned to receive inactive placebo (n = 19; group C) or a low dose (1 mg,n = 10; group D1), or a high dose (2 or 3mg,n = 9; group D2) of diltiazem in a double-blind manner. The agent was administered directly into the coronary artery via a balloon catheter following a control balloon inflation. Chest pain score (maximum, 10) and the magnitude of ischemic ST elevation on standard and intracoronary electrocardiograms (ECGs) during a balloon inflation were assessed in the control and posttreatment periods. After the administration of diltiazem, the chest pain score was significantly decreased in group D1 (control: 5.1 ± 3.6, posttreatment: 3.8 ± 3.1,P < 0.01) and group D2 (3.4 ± 2.5 vs 2.5 ± 2.0,P < 0.01), but not in group C (4.1 ± 3.1 vs 3.7 ± 3.3, difference not significant). The magnitude of ST elevation relative to the control on standard and intracoronary ECGs was significantly smaller in groups D1 and D2 than in group C (standard ECG; D1: 51.8 ± 10.6% of control, D2: 41.6 ± 28.7% vs C: 93.3 ± 15.6% and intracoronary ECG; D1: 47.1 ± 11.7% of control, D2: 27.5 ± 26.9% vs C: 94.6 ± 29.3%, allP < 0.01). Although systolic blood pressure decreased slightly in groups D1 and D2, there was no significant correlation between the change in ST elevation and the change in the rate-pressure product. Pretreatment with a small dose of intracoronary diltiazem attenuated myocardial ischemia during PTCA and this pretreatment may enable us to perform balloon inflation for a longer period.     

静脉注射地尔硫对室上性心动过速的即时疗效和电生理作用

本文通过食管程序电刺激,对20例阵发性室上性心动过速(简称室上速)患者,其中房室结内折返性心动过速(AVNRT)5例,房室折返性心动过速(AVRT)15例,研究静脉注射地尔硫或维拉帕米(0.2mg/kg)的即时疗效和电生理作用。结果表明:①两药均有明显抑制房室结传导作用,对旁路的传导无明显抑制;②对正常窦房结功能者无明显抑制作用;③单剂静脉注射时血压轻度降低,副作用轻;④终止诱发或自发性室上速的有效率分别为60%(地尔硫组)和80%(维拉帕米组)。     

Reversal of acute theophylline toxicity by calcium channel blockers in dogs and rats

Theophylline, widely used in the treatment of pulmonary diseases, has a narrow therapeutic index; the recommended plasma levels being 10–20 μg/ml in humans. The misuse or abuse of theophylline can cause life-threatening central nervous system and cardiovascular effects. Increased intracellular Ca²⁺ levels are thought to play an important role in theophylline toxicity and death. The objective of this study was to determine whether Ca²⁺ channel blockers, e.g. verapamil, nifedipine, or diltiazem, prevent sudden death caused by theophylline treatment in rats and dogs. Groups of Sprague-Dawley rats were treated with theophylline alone (150 mg/kg i.p.) or with theophylline pretreatment followed by administration of verapamil (0.25 to 0.5 mg/kg i.p.), nifedipine (0.25 to 1.0 mg/kg i.p.), or diltiazem (0.5 to 1.0 mg/kg i.p.), 2.5 to 15 min later. The rats were observed for toxic signs and survival over a period of 15 days. All three calcium channel blockers significantly reduced the theophylline-induced sudden death in rats. In a separate study, neither verapamil (0.5 mg/kg i.p.) nor nifedipine (1.0 mg/kg i.p.) prevented the theophylline-induced myocardial necrosis in the rat. In beagle dogs, verapamil (0.5 mg/kg i.v.) prevented theophylline (15 mg/kg/min i.v. for 10 min)-induced hypotension, arrhythmias, and sudden death. Our results support previously reported findings that calcium plays a major role in theophylline-induced toxicity and death.