Reves J G, Kissin I, Fournier S E, Smith L R
Anesth Analg. 1984 Feb;63(2):97-100.
Hearts were excised from 30 male Sprague-Dawley rats and perfused in a modified Langendorff system to examine the interactions of fentanyl and diazepam on myocardial contractility as measured by left ventricular dP/dtmax. Various concentrations of fentanyl and diazepam were added to the nonrecirculating 37 degrees C perfusate to determine ED25 and ED50 for depression of dP/dtmax. Combinations of fentanyl and diazepam at a fixed negative inotropic potency ratio of 1:1 were used to determine the ED25 and ED50 of this combination. Isobolographic analyses performed at ED25 and ED50 revealed that the negative inotropic interaction of fentanyl and diazepam is purely additive. It is unlikely that a supraadditive negative inotropic effect can explain the supraadditive hemodynamic depression reported in humans when diazepam and fentanyl are combined; perhaps systemic vascular effects of this drug combination account for the clinical drug interactions.
从30只雄性Sprague-Dawley大鼠身上取出心脏，在改良的Langendorff系统中进行灌注，以研究芬太尼和地西泮对心肌收缩力的相互作用，心肌收缩力通过左心室dP/dtmax来测量。将不同浓度的芬太尼和地西泮添加到37℃的非循环灌注液中，以确定降低dP/dtmax的ED25和ED50。以1:1的固定负性肌力效价比使用芬太尼和地西泮的组合来确定该组合的ED25和ED50。在ED25和ED50进行的等效线分析表明，芬太尼和地西泮的负性肌力相互作用完全是相加的。当联合使用地西泮和芬太尼时，超相加的负性肌力作用不太可能解释人类报告的超相加血流动力学抑制；也许这种药物组合的全身血管效应可以解释临床药物相互作用。
