Pijl A J, Van Wezel H B, Koolen J J, Piek J J, Koch K, Swaan A, David G K, Visser C A, Van Zwieten P A
Department of Anaesthesiology, University of Amsterdam, The Netherlands.
Br J Clin Pharmacol. 1995 May;39(5):531-5. doi: 10.1111/j.1365-2125.1995.tb04491.x.
The present study was designed to evaluate the potential anti-ischaemic activity of R 56865 in patients with coronary artery disease, scheduled to undergo percutaneous transluminal coronary angioplasty (PTCA). At baseline a complete haemodynamic profile, including cardiac output and coronary sinus blood flow (CSBF) was obtained. In addition, left ventricular pressure and contractility parameters were measured. These parameters were also measured before and after additional balloon inflations, preceded by placebo and R 56865 i.v. R 56865 was infused intravenously at three different dosages, namely: 20 mg (n = 8), 30 mg (n = 2), 40 mg (n = 2). No significant differences were observed between placebo and R 56865 (20 mg) concerning time to onset and duration of ST-segment changes and symptomatic angina pectoris, respectively. The other parameters did not show differences compared with the baseline values when R 56865 (20 and 30 mg) was infused. However, the two patients receiving a dose of 40 mg R 56865 developed a dramatic decrease in systolic and diastolic blood pressure, left ventricular (LV) systolic pressure, peak positive dP/dt and the CSBF (ranging from 30-50%), while the LV end-diastolic pressure increased by 100%. The two patients who received this dose became pale and cyanotic and did not respond to verbal commands. In summary, no anti-ischaemic effects of R 56865 were observed under these conditions, whereas at the highest dose (40 mg) R 56865 induced hypotension and a reduction in cardiac contractile force.
本研究旨在评估R 56865对计划接受经皮腔内冠状动脉成形术(PTCA)的冠心病患者的潜在抗缺血活性。在基线时,获取了包括心输出量和冠状窦血流量(CSBF)在内的完整血流动力学概况。此外,还测量了左心室压力和收缩性参数。在安慰剂和静脉注射R 56865后进行额外球囊充气前后,也测量了这些参数。R 56865以三种不同剂量静脉输注,即:20毫克(n = 8)、30毫克(n = 2)、40毫克(n = 2)。安慰剂和R 56865(20毫克)在ST段改变的起效时间和持续时间以及症状性心绞痛方面未观察到显著差异。当输注R 56865(20毫克和30毫克)时,与基线值相比,其他参数未显示差异。然而,接受40毫克R 56865剂量的两名患者出现收缩压和舒张压、左心室(LV)收缩压、峰值正向dP/dt和CSBF急剧下降(范围为30 - 50%),而LV舒张末期压力增加了100%。接受该剂量的两名患者面色苍白、发绀,对言语指令无反应。总之,在这些条件下未观察到R 56865的抗缺血作用,而在最高剂量(40毫克)时,R 56865诱导了低血压和心脏收缩力降低。