International nifedipine trial on antiatherosclerotic therapy (intact)

Summary A number of animal studies revealed an inhibition or retardation of the progression of atherosclerosis by calcium-antagonists. Encouraged by these studies, a multicenter trial on the progression of coronary artery disease (CAD) in man was initiated testing the antisclerotic effect of nifedipine against placebo in 426 patients with mild to moderate coronary disease over 3 years. All patients underwent coronary angiography before entering the trial and will be restudied after 3 years; changes of the coronary artery lumen size are quantitatively assessed by a computer-assisted system (CAAS). INTACT (International Trial on Antiatherosclerotic Coronary Therapy) is therefore the first randomized prospective study on the progression of CAD based on a quantitated anigraphic control of the coronary system.This report presents the design of this still-ongoing study as well as inclusion and exclusion criteria. The quantitative evaluation of the coronary angiograms and the mode of compliance test are described in detail. A number of baseline data as well as the preliminary results of the quantitative evaluation of the first coronary angiograms are presented.Beside the results on the effect of the calcium-antagonist nifedipine on the progression of CAD, INTACT might also supply information on the antiatherosclerotic potency of other drugs administered additionally (beta-blockers and nitrates) and of HDL-cholesterol.     

Comparison of acute haemodynamic effects of nifedipine and isosorbide dinitrate in patients with heart failure following acute myocardial infarction

The acute haemodynamic effects of nifedipine (10 mg sublingually) and isosorbide dinitrate (5 mg sublingually) were compared in 13 patients with heart failure due to acute myocardial infarction. Nifedipine induced a significant reduction in systolic (from 122 ± 5 to 107 ± 3 mm Hg: mean ± SEM; P < 0.002) and diastolic blood pressure (from 85 ± 3 to 75 ± 2 mm Hg; P < 0.01). Heart rate did not change significantly, nor did mean right atrial pressure. The mean pulmonary arterial pressure was lowered from 31 ± 2 to 27 ± 2 mm Hg (P < 0.005). The left ventricular filling pressure decreased from 24 ± 1 to 19 ± 1 mm Hg (P < 0.0001). A significant increase in cardiac index (from 2.33 ± 0.13 to 2.69 ± 0.15 l/min per m²; P < 0.001) and in stroke volume index (from 24 ± 2 to 28 ± 2 ml/beats per m²; P < 0.005) was registered. Systemic vascular resistance fell from 1742 ± 145 to 1308 ± 85 dynes/sec per cm⁻⁵ (P < 0.00005). After isosorbide dinitrate was administered a significant reduction in mean right atrial pressure (from 9.5 ± 1.6 to 5.1 ± 1.2 mm Hg; P < 0.0001), in mean pulmonary arterial pressure (from 32 ± 1 to 23 ± 1 mm Hg; P < 0.00001) and in left ventricular filling pressure (from 23 ± 1 to 16 ± 1 mm Hg; P < 0.0001) was seen. No significant change in systolic and diastolic blood pressure, heart rate, cardiac index, stroke volume index and systemic vascular resistance was registered. No side-effects were seen after nifedipine and isosorbide dinitrate were administered.     

硝苯地平联合拉贝洛尔对妊高征患者血管功能、凝血功能及妊娠结局的影响

目的 观察硝苯地平联合拉贝洛尔对妊娠高血压综合征(简称妊高征)患者血管功能、凝血功能及妊娠结局的影响.方法 随机选择2019年1月至2020年12月来我院诊治的150例妊高征患者为研究对象,按随机数字表法将其分为对照组和观察组,各75例.对照组采用硝苯地平治疗,观察组采用硝苯地平联合拉贝洛尔治疗.比较两组的血压控制效果...     

Calcium antagonists: definition and mode of action

Summary The term calcium antagonist has been used for more than a decade to describe a group of drugs whose negative inotropism is overcome by calcium. Because this term lacks specificity with respect to a precise mode of action, and implies a classical receptor-agonist-antagonist relationship, its continued use should be questioned. Drugs belonging to this group are verapamil, D600, nifedipine and diltiazem. They inhibit the slow inward current of the action potential and would more appropriately be called slow channel inhibitors. The group is heterogenous and may have to be subclassified.The negative inotropism of these drugs can be attributed to a reduction of the slow calcium current. The function of most intracellular organelles is unaffected. Studies with radioactively labelled verapamil show tight binding to glycolipids or glycoproteins in the sarcolemma. Consequent change in the conformational state of the cell membrane could inhibit the slow calcium current.The ability of these drugs to protect heart muscle against the deleterious effects of ischaemia and reperfusion may reflect their negative inotropism, with consequent maintenance of tissue ATP above the levels needed to maintain intracellular Ca²⁺ homeostasis, rather than a direct inhibitory effect on calcium influx during ischaemia or on reperfusion.With 6 figures and 1 tableThe investigations were carried out during the tenure of a grant from the Medical Research Council of Great Britain and the NH and MRC of Australia.     

Nisoldipine tablets once daily versus nifedipine capsules three times daily in patients with stable effort angina pectoris pretreated with atenolol

Summary Treatment with nisoldipine (2×10 mg tablets once daily) and nifedipine (2×10 mg capsules three times daily) in patients with severe, but stable effort angina pretreated with atenolol (100 mg once daily in 19 patients and 50 mg once daily in one patient) were compared for their effects on bicycle exercise tolerance and their adverse effects in a randomized 2×4 week, double-blind, double-dummy crossover study. All patients had multivessel disease, 16 patients had occlusion of at least one vessel, and eight patients had a history of myocardial infarction. Two patients left the study during the initial nisoldipine period, one because of aggravation of the angina and the other because of suspected allergic reaction. Addition of nifedipine to atenolol treatment significantly improved the variables measured for severity of angina, such as time of exercise until 1 mm and 2 mm ST-segment depression, total exercise time and total workload. In contrast, no such improvement was noted after the addition of nisoldipine to atenolol. However, nisoldipine resulted in a significant prolongation of the time to the initiation of chest discomfort, the maximum heart rate, and the double product.In atenolol-treated patients with severe effort angina pectoris, nifedipine 20 mg tid improved exercise capacity, while nisoldipine 20 mg once daily did not have a similar effect.     

卡托普利与缓释硝苯地平治疗对高血压病患者运动血压的影响

目的:探讨原发性高血压(EH)经治疗血压稳定下降后,运动后血压反应是否恢复正常,以及观察卡托普利与缓释硝苯地平治疗有无差异。方法:观察正常成人22例,44例EH患者随机分为卡托普利和硝苯地平治疗2组。卡托普利始用12.5mg,2次/d,缓释硝苯地平始用10mg,2次/d,治疗2周,血压未降至正常者,分别加至25mg,2次/d或20mg,2次/d;观察3个月。观察结束前1周测定运动前、运动后即刻、5、10、15min血压,计血压恢复至运动前水平的时间(血压恢复时间)。结果:正常组运动后SBP和DBP升高幅度分别为(12.6±3.3)mmHg和(-0.1±2.6)mmHg,血压恢复时间为(5.9±2.0)min;高血压治疗2组虽然血压得到满意控制,但上述参数仍明显增加;但卡托普利组运动后SBP/DBP升幅明显小于硝苯地平组[(14.9±3.2)mmHg/(8.8±3.3)mmHg比(18.9±7.7)mmHg/(11.6±4.5mm)Hg,P均<0.05)];血压恢复时间更短[(9.8±4.6)min比(13.3±5.3)min,P<0.05)]。结论:高血压病患者即使血压得到有效控制,运动血压增幅和血压恢复时间仍明显大于正常血压者。与缓释硝苯地平比较,卡托普利治疗运动血压增幅更小,血压恢复时间更短。     

Calcium,Nifedipine and Arrhythmias in Isolated Rat Atria

Abstract Arrhythmias were induced in isolated rat atrial muscle preparations by increasing the calcium concentration of the Ringer solution, while the potassium concentration was kept low. A rise in the resting tension occurred simultaneously. The release of aspartate aminotransferase (ASAT) from the fibrillating atria was not higher than the release from non-fibrillating atria pretreated with a calcium-antagonistic drug, nifedipine 100 μg/l. It is suggested that calcium-induced rat atrial arrhythmias in the present experiments are caused by a direct effect on calcium influx through the excitable membrane and not as a result of myocardial lesion caused by calcium overload.     

黄芪对心房收缩力及心房钠尿肽分泌的影响

目的：观察黄芪对家兔心房收缩力及心房钠尿肽分泌的影响。方法：采用家兔离体心房灌流模型，处理0.002,0.002 5,0.003 g·L^-1的黄芪水提取液观察家兔心房收缩力及心房钠尿肽分泌的变化，并选择最佳剂量探讨其作用机制。心房钠尿肽含量的测定采用放射免疫法。结果：3个剂量的黄芪水提取液使离体家兔心房每搏输出量由给药前的(694.70±0.01) μL·g^-1分别增加到(1 003.00±8.80)，(1 120.00±17.71)，(1 195.00±8.21) μL·g^-1(与给药前比较，分别P<0.05；P<0.01及P<0.001)；并使心房搏动压由给药前的(0.82±0.01) kPa分别增加至(0.86±0.01)，(0.96±0.01)，(1.02±0.01) kPa(与给药前比较，分别P<0.01；P<0.001及P<0.001)，且呈现浓度依赖性特征，表明黄芪可增加家兔心房收缩力。0.002 5 g·L^-1黄芪水提取液显著抑制心房钠尿肽的分泌［给药前心房钠尿肽含量为(18.74±0.02 ) ng·min^-1·g^-1，给药后为(12.97±0.14) ng·min^-1·g^-1；与给药前比较P<0.001］。L-型Ca²⁺通道阻断剂硝苯地平(1.0 μmol·L^-1)及逆向Na⁺-Ca²⁺交换体抑制剂KB-R 7943(10.0 μmol·L^-1)阻断了黄芪增强心房收缩力的作用，但均未能改变黄芪对心房钠尿肽分泌的抑制效应。结论：黄芪主要通过影响L-型Ca²⁺通道及Na⁺-Ca²⁺交换体增强心房收缩力，并对心房钠尿肽分泌具有抑制性调节作用。     

硝苯地平与银杏黄酮的体外代谢性相互作用

 目的通过体外代谢获得药物相互作用的有关数据,以预测临床联合用药时发生代谢性药物相互作用的可能性。方法以HPLC测定孵育液中剩余银杏黄酮的浓度,计算共孵育药物硝苯地平对银杏黄酮3个苷元的IC₅₀值和K_i值;以HPLC测定孵育液中硝苯地平的浓度,计算其代谢抑制率。结果硝苯地平与银杏黄酮进行体外共孵育时,代谢互受影响。结论两药合用时宜慎重。