De Wildt D J, Hillen F C, Rauws A G, Sangster B
Br J Pharmacol. 1983 Jun;79(2):461-9. doi: 10.1111/j.1476-5381.1983.tb11019.x.
In spontaneously breathing rats, continuous infusion of etomidate with and without fentanyl caused a slight decrease in blood pressure and heart rate. Coadministration of fentanyl and etomidate in order to obtain full anaesthesia and analgesia resulted in respiratory depression. In artificially ventilated rats both etomidate as well as the anaesthetic combination caused a strong reduction in aortic flow and an increase in total peripheral resistance. A single infusion of etomidate did not change blood pressure. Etomidate combined with fentanyl reduced blood pressure. Under adjusted ventilation blood pressure, aortic flow, max(dF/dt) and heart rate were progressively reduced during a 4 h period. In contrast, urethane anaesthesia reduced aortic flow to a minor extent. Total peripheral resistance and max(dF/dt) were hardly affected. The slightly reduced blood pressure and blood gas variables remained stable during the experiment. From pharmacokinetic studies it was established that effective etomidate plasma levels were maintained constant during the experimental period. Pharmacokinetic interaction between etomidate and fentanyl did not occur. It is concluded that for anaesthesia of longer duration during cardiovascular experiments in rats, urethane is preferable to etomidate/fentanyl because it does not cause serious changes in basal haemodynamic variables.
在自主呼吸的大鼠中,持续输注依托咪酯(无论是否联用芬太尼)都会导致血压和心率略有下降。联用芬太尼和依托咪酯以实现完全麻醉和镇痛会导致呼吸抑制。在人工通气的大鼠中,依托咪酯以及麻醉合剂均会导致主动脉血流显著减少和总外周阻力增加。单次输注依托咪酯不会改变血压。依托咪酯与芬太尼联用会降低血压。在调整通气的情况下,血压、主动脉血流、最大(dF/dt)和心率在4小时内逐渐降低。相比之下,氨基甲酸乙酯麻醉对主动脉血流的降低程度较小。总外周阻力和最大(dF/dt)几乎未受影响。实验期间,略有降低的血压和血气变量保持稳定。药代动力学研究表明,实验期间依托咪酯的有效血浆水平保持恒定。依托咪酯和芬太尼之间未发生药代动力学相互作用。得出的结论是,在大鼠心血管实验中进行较长时间麻醉时,氨基甲酸乙酯比依托咪酯/芬太尼更可取,因为它不会引起基础血流动力学变量的严重变化。