D'Aubioul J, Van Gerven W, Van de Water A, Xhonneux R, Reneman R S
Eur J Pharmacol. 1984 Apr 13;100(1):79-84. doi: 10.1016/0014-2999(84)90317-0.
The cardiovascular and some respiratory effects of alfentanil, a potent and short-acting morphinomimetic, were studied in conscious (n = 6) and anaesthetized, artificially ventilated dogs (n = 7). The compound was injected intravenously in increasing doses of 12.5, 12.5, 25, 50, 100, 200, 400 and 800 micrograms X kg-1 in the conscious dogs and of 0.16, 0.32, 0.64, 1.25, 2.5 and 5 mg X kg-1 in the anaesthetized animals. In the conscious dogs, the heart rate decreased significantly reaching a maximum decrease after the injection of 400 micrograms X kg-1 X PCO2 and arterial and venous lactate concentrations increased, while PO2, pH and base excess decreased significantly. At higher dose levels (100-400 micrograms X kg-1) short periods of convulsions were seen. The most pronounced change in the anaesthetized dogs was a significant fall in LVdP/dt max and LV dP/dt max/P, associated with a rise in left ventricular end-diastolic pressure following the injection of 5 mg X kg-1, suggesting negative inotropic properties at this high dose level. Most of the animals showed A-V dissociations which disappeared at higher doses. All animals survived. These findings indicate that alfentanil is a safe analgesic as far as the effects on the cardiovascular system are concerned. High doses are tolerated well, especially when the animals are artificially ventilated. The short periods of convulsions, seen only in the awake dogs, may have been facilitated by the low PO2 levels reached (median value: 9 kPa).
研究了强效短效拟吗啡药阿芬太尼对清醒犬(n = 6)和麻醉、人工通气犬(n = 7)心血管及部分呼吸的影响。分别以递增剂量静脉注射该化合物,清醒犬的剂量为12.5、12.5、25、50、100、200、400和800微克/千克,麻醉动物的剂量为0.16、0.32、0.64、1.25、2.5和5毫克/千克。在清醒犬中,注射400微克/千克后心率显著下降至最大降幅,同时PCO2、动脉血和静脉血乳酸浓度升高,而PO2、pH和碱剩余显著降低。在较高剂量水平(100 - 400微克/千克)时可见短时间惊厥。麻醉犬最明显的变化是注射5毫克/千克后左心室dp/dt max和左心室dp/dt max/P显著下降,同时左心室舒张末期压力升高,提示在该高剂量水平具有负性肌力作用。大多数动物出现房室分离,高剂量时消失。所有动物均存活。这些发现表明,就对心血管系统的影响而言,阿芬太尼是一种安全的镇痛药。高剂量耐受性良好,尤其是在动物人工通气时。仅在清醒犬中出现的短时间惊厥,可能与所达到的低PO2水平(中位数:9 kPa)有关。