Heerdt Paul M, Kang Richard, The' Andrew, Hashim Mir, Mook Robert J, Savarese John J
Department of Anesthesiology, Weill Medical College of Cornell University, New York, New York 10021, USA.
Anesthesiology. 2004 Apr;100(4):846-51. doi: 10.1097/00000542-200404000-00014.
This investigation determined the cardiopulmonary side effects of a novel nondepolarizing neuromuscular blocking drug with an ultrashort duration of action in anesthetized male beagles.
The ED95 for GW280430A was first determined in four animals. These data were then used to guide bolus dosing in multiples of ED95 in six dogs instrumented for hemodynamic measurements as well as inspiratory pressure and pulmonary compliance. Cardiopulmonary data were compared before and after the conclusion of a 60- to 90-min GW280430A infusion and in response to subsequent incremental bolus dosing starting with 3.125 x ED95. An adverse response was regarded as an alteration of 10% or greater in any variable. Arterial blood was obtained for histamine analysis before and 1 min after each dose.
The ED95 of GW280430A was 0.064 +/- 0.01 mg/kg, and stable neuromuscular blockade was maintained with infusion of 0.012 +/- 0.002 mg.kg(-1).min(-1). With the exception of a late 14% increase in heart rate, there were no cardiopulmonary changes during infusion. Bolus dosing produced no cardiopulmonary change until a decrease in mean arterial pressure was elicited in four of six dogs at 25 x ED95. This response was modest, transient, and associated with a concomitant increase in plasma histamine concentration. There were no accompanying changes indicative of direct myocardial depression, pulmonary vasoconstriction, or bronchospasm.
These data indicate that GW280430 does not produce demonstrable cardiovascular effects in the anesthetized dog until doses far in excess of the ED95 are administered as a bolus.
本研究确定了一种新型超短效非去极化神经肌肉阻滞药物在麻醉雄性比格犬中的心肺副作用。
首先在四只动物中确定GW280430A的ED95。然后将这些数据用于指导六只安装了血流动力学测量以及吸气压力和肺顺应性测量仪器的犬，以ED95的倍数进行推注给药。在60至90分钟的GW280430A输注结束前后以及随后从3.125×ED95开始的递增推注给药后，比较心肺数据。不良反应被视为任何变量有10%或更大的改变。在每次给药前和给药后1分钟采集动脉血进行组胺分析。
GW280430A的ED95为0.064±0.01mg/kg，以0.012±0.002mg·kg-1·min-1的速度输注可维持稳定的神经肌肉阻滞。除心率在后期增加14%外，输注期间未出现心肺变化。推注给药直至6只犬中有4只在25×ED95时平均动脉压下降之前，未引起心肺变化。这种反应轻微、短暂，且与血浆组胺浓度同时升高有关。没有伴随的变化表明有直接的心肌抑制、肺血管收缩或支气管痉挛。
这些数据表明，在麻醉犬中，直到以推注方式给予远超过ED95的剂量时，GW280430才会产生明显的心血管效应。
