de Mey C, Enterling D
SK&F Institute for Applied Clinical Pharmacology, Goettingen, FRG.
Methods Find Exp Clin Pharmacol. 1988 Jan;10(1):57-64.
Thirty-five male normal subjects underwent gradual passive upright tilt (1 minute at 15 degree, 2 minutes at 45 degree and 7 minutes at 85 degree) on a total of 256 occasions, in drug-free condition or after administration of placebo. Although a cardio-acceleratory and vasopressor response prevailed, seven subjects experienced imminent syncope on 9 occasions, after 2 to 7 minutes erect standing. These reactions were hypotensive in nature, and preceded by (5 instances) or concurrent with (3 instances) a sudden drop of the initially adequately rising heart rate. These reactions are likely to be of vagal origin. All reactions occurred suddenly and unexpectedly and improved rapidly when the subject was tilted back to supine position. Imminent syncopes on passive upright tilt appeared to be incidental phenomena occurring in subjects who uneventfully underwent previous or subsequent tilting, either on the same day or on another day. The potential severity of these reactions, their unpredictability and their lack of reproducibility restrict the usefulness of passive upright tilt as a test procedure in drug research. In the event that such reactions would appear after exposure to an investigational drug, it cannot be proven beyond reasonable doubt that the reaction is caused by the drug, is a variant response intrinsic to the test procedure, or a drug-related enhancement of the onset and/or severity of such a variant response.
35名男性正常受试者在未用药或服用安慰剂后，总共256次接受了逐渐被动直立倾斜试验（15度倾斜1分钟、45度倾斜2分钟、85度倾斜7分钟）。尽管主要表现为心脏加速和血管加压反应，但有7名受试者在直立站立2至7分钟后，9次出现即将晕厥的情况。这些反应本质上是低血压性的，在最初心率充分上升后，有5次先出现心率突然下降，有3次与心率突然下降同时出现。这些反应可能起源于迷走神经。所有反应均突然且意外地发生，受试者向后倾斜至仰卧位后迅速好转。被动直立倾斜试验中即将出现的晕厥似乎是偶然现象，发生在之前或之后在同一天或另一天顺利完成倾斜试验的受试者身上。这些反应的潜在严重性、不可预测性以及缺乏可重复性限制了被动直立倾斜试验在药物研究中的实用性。如果在接触研究药物后出现此类反应，无法在合理怀疑之外证明该反应是由药物引起的，是试验程序固有的变异反应，还是药物相关的此类变异反应发作和/或严重程度的增强。
