Azari D M, Cork R C
Department of Anesthesiology, University of Arizona, Tucson.
Anesth Analg. 1993 Aug;77(2):324-9. doi: 10.1213/00000539-199377020-00019.
To compare the direct myocardial effects of thiopental and propofol, concentration-contractility curves were determined by using an isolated guinea pig left atrial preparation. Contractility was measured as peak twitch tension, maximum rate of contraction (dT/dt), and maximum rate of relaxation (-dT/dt). Drug concentrations ranged from 56 microM (10 micrograms/mL) to 2800 microM (500 micrograms/mL) propofol and 3.8 microM (1 microgram/mL) to 190 microM (50 micrograms/mL) thiopental. Data were fitted to a sigmoidal inhibitory pharmacodynamic model in which an increasing incremental drug concentration is needed to cause a consistent incremental effect. Comparisons were then made of the drug concentrations at which a 50% inhibition in contractility was noted (IC50). To compare drugs on an equi-anesthetic basis, comparisons also were made between IC50 values normalized to anesthetic concentrations needed to produce anesthesia (67.8 microM and 28.1 microM for thiopental and propofol, respectively). Data from seven atrial preparations for thiopental and seven atrial preparations for propofol were analyzed. The IC50 (microM) for peak twitch tension were 20.9 +/- 6.3 and 96.6 +/- 10.1 (P < 0.05), for dT/dt were 21.1 +/- 5.9 and 86.9 +/- 8.3 (P < 0.05), and for -dT/dt were 21.0 +/- 6.1 and 84.3 +/- 9.2 (P < 0.05) for thiopental and propofol, respectively. When the normalized IC50 were compared, the differences between anesthetics became greater. For guinea pig left atria in vitro, thiopental is a more potent myocardial depressant than propofol, especially when compared relative to anesthetic potencies; neither anesthetic preferentially affects peak twitch tension, maximum rate of contraction, or maximum rate of relaxation.
为比较硫喷妥钠和丙泊酚对心肌的直接作用,采用离体豚鼠左心房标本测定浓度 - 收缩力曲线。收缩力通过峰值抽搐张力、最大收缩速率(dT/dt)和最大舒张速率(-dT/dt)来衡量。丙泊酚的药物浓度范围为56微摩尔/升(10微克/毫升)至2800微摩尔/升(500微克/毫升),硫喷妥钠的药物浓度范围为3.8微摩尔/升(1微克/毫升)至190微摩尔/升(50微克/毫升)。数据拟合至S形抑制药效学模型,其中需要增加药物浓度增量才能产生一致的效应增量。然后比较观察到收缩力抑制50%时的药物浓度(IC50)。为在等效麻醉基础上比较药物,还对根据产生麻醉所需的麻醉浓度进行归一化后的IC50值进行了比较(硫喷妥钠和丙泊酚分别为67.8微摩尔/升和28.1微摩尔/升)。分析了来自七个硫喷妥钠心房标本和七个丙泊酚心房标本的数据。硫喷妥钠和丙泊酚的峰值抽搐张力IC50(微摩尔/升)分别为20.9±6.3和96.6±10.1(P<0.05),dT/dt的IC50分别为21.1±5.9和86.9±8.3(P<0.05),-dT/dt的IC50分别为21.0±6.1和84.3±9.2(P<0.05)。当比较归一化的IC50时,麻醉剂之间的差异变得更大。对于体外豚鼠左心房,硫喷妥钠比丙泊酚是更强效的心肌抑制剂,尤其是相对于麻醉效能进行比较时;两种麻醉剂均不会优先影响峰值抽搐张力、最大收缩速率或最大舒张速率。