Silke B, Sharma S K, Verma S P, Midtbo K A, Reynolds G, Taylor S H
Br J Clin Pharmacol. 1987 Feb;23(2):165-72. doi: 10.1111/j.1365-2125.1987.tb03025.x.
To obtain multiple dose-response haemodynamic and radionuclide data on i.v. diltiazem, 12 ischaemic patients were studied during routine catheterization. At rest, following a 20 min stable control period, the effects of four doses (0.0625, 0.0625, 0.125 and 0.25 mg kg-1 diltiazem at 5 min intervals) were measured in the 3-5 min following i.v. injection. The exercise effects of the cumulative 0.5 mg kg-1 dosage were assessed by comparing a control and post drug period of supine bicycle exercise. The increase in plasma diltiazem levels correlated linearly with the administered dose and achieved therapeutic levels. There were significant dose-related reductions in systemic arterial blood pressure and vascular resistance index; the heart rate fell and cardiac stroke index increased. The calculated double-product (heart rate X systolic blood pressure) was significantly reduced. The left ventricular filling pressures, ejection fraction and cardiac volumes were unaltered. During supine bicycle exercise, the systemic diastolic blood pressure, heart rate and calculated double-product were reduced without change in other parameters. Over the dose range 0.0625-0.5 mg kg-1, diltiazem acutely increased cardiac stroke index and reduced resting heart rate. These haemodynamic data, taken together with its described coronary vasodilator activity suggest that its role in acute vasospastic angina and during angiographic procedures ought to be explored further.
为获取静脉注射地尔硫䓬的多剂量反应血流动力学和放射性核素数据，对12例缺血性患者在常规导管插入术期间进行了研究。静息状态下，在20分钟稳定的对照期后，于静脉注射后3 - 5分钟测量四个剂量（0.0625、0.125和0.25毫克/千克，间隔5分钟）的效果。通过比较仰卧位自行车运动的对照期和用药后时期，评估累积剂量0.5毫克/千克的运动效果。血浆地尔硫䓬水平的升高与给药剂量呈线性相关，并达到治疗水平。全身动脉血压和血管阻力指数有显著的剂量相关降低；心率下降，心搏指数增加。计算得出的双乘积（心率×收缩压）显著降低。左心室充盈压、射血分数和心脏容积未改变。在仰卧位自行车运动期间，全身舒张压、心率和计算得出的双乘积降低，其他参数无变化。在0.0625 - 0.5毫克/千克的剂量范围内，地尔硫䓬急性增加心搏指数并降低静息心率。这些血流动力学数据，连同其所述的冠状动脉血管舒张活性，表明其在急性血管痉挛性心绞痛和血管造影术中的作用应进一步探索。
