Komai H, DeWitt D E, Rusy B F
Anesth Analg. 1985 Apr;64(4):400-4.
The effect of etomidate on the developed force of isometrically contracting rabbit papillary muscles in modified Krebs-Henseleit bicarbonate medium was evaluated under various stimulation conditions to gain insight into the mechanism underlying the negative inotropic effect of this anesthetic. Myocardial depressant effects of etomidate (2 and 4 mg/L) on steady-state contractions at low stimulation frequencies (0.1-0.5 Hz) were more pronounced than the effects on either steady-state contraction at high stimulation frequencies (1.0-2.0 Hz) or the effects on post-rest potentiated state contractions. Increases in the concentration of extracellular Ca2+ from an initial level of 2.5 mM to 3.4-4.0 mM reversed the effect of 2 mg/L of etomidate, whereas an increase to 4.6-5.0 mM was required to reverse the effect of 4 mg/L of etomidate. The dependence of post-rest potentiation on the duration of the preceding rest period was virtually unaffected by etomidate. These results suggest that etomidate inhibits the influx of extracellular Ca2+ but has little effect on the availability of intracellular Ca2+ required for the activation of myocardial contractile activity. Because the concentrations of etomidate required to produce negative inotropic responses in the present study are substantially greater than those likely to be achieved under clinical conditions, the present results also suggest that negative inotropism is unlikely in patients with normal hearts.
在改良的 Krebs-Henseleit 碳酸氢盐培养基中，评估依托咪酯对兔乳头肌等长收缩力的影响，以深入了解这种麻醉药负性肌力作用的潜在机制。依托咪酯（2 和 4 mg/L）在低刺激频率（0.1 - 0.5 Hz）下对稳态收缩的心肌抑制作用比在高刺激频率（1.0 - 2.0 Hz）下对稳态收缩或对静息后增强状态收缩的作用更明显。将细胞外 Ca2+ 浓度从初始水平 2.5 mM 增加到 3.4 - 4.0 mM 可逆转 2 mg/L 依托咪酯的作用，而增加到 4.6 - 5.0 mM 才能逆转 4 mg/L 依托咪酯的作用。依托咪酯对静息后增强对先前静息期持续时间的依赖性几乎没有影响。这些结果表明，依托咪酯抑制细胞外 Ca2+ 的内流，但对激活心肌收缩活动所需的细胞内 Ca2+ 的可用性影响很小。由于在本研究中产生负性肌力反应所需的依托咪酯浓度远高于临床条件下可能达到的浓度，因此本研究结果还表明，正常心脏患者不太可能出现负性肌力作用。
