Meyer E C, Sommers D K, Avenant J C
Department of Pharmacology, University of Pretoria, South Africa.
Eur J Clin Pharmacol. 1991;41(6):517-9. doi: 10.1007/BF00314977.
We have used systolic time intervals (STI) to measure inotrophy and chronotropy as indirect measures of the actions of noradrenaline, in order to ascertain whether the depletion of cardiac noradrenaline stores which has been shown to occur in laboratory rats after chronic verapamil treatment could be demonstrated in healthy volunteers. Placebo, verapamil, or atenolol were given by slow intravenous injection to 8 healthy volunteers and QS2I, LVETI, and PEP/LVET were measured. Verapamil pretreatment resulted in a positive inotropic state. Intravenous verapamil after oral pretreatment caused accentuated negative inotropic and chronotropic responses as compared with acute verapamil without pretreatment. We postulate that the observed initial inotropic effect may be in part due to an increase in the amount of noradrenaline available to the myocardium intrasynaptically, and that the accentuated negative response after intravenous or oral verapamil may result from a decrease in cardiac noradrenaline storage.
我们使用收缩期时间间期(STI)来测量心肌收缩力和变时性,作为去甲肾上腺素作用的间接指标,以确定在慢性维拉帕米治疗后的实验大鼠中已被证实出现的心脏去甲肾上腺素储备耗竭情况,是否也会在健康志愿者中出现。对8名健康志愿者缓慢静脉注射安慰剂、维拉帕米或阿替洛尔,并测量QS2I、LVETI和PEP/LVET。维拉帕米预处理导致正性肌力状态。与未预处理的急性维拉帕米相比,口服预处理后静脉注射维拉帕米引起更明显的负性肌力和变时反应。我们推测,观察到的初始正性肌力作用可能部分归因于突触内可用于心肌的去甲肾上腺素量增加,而静脉注射或口服维拉帕米后更明显的负性反应可能是由于心脏去甲肾上腺素储备减少所致。