Warren J B, Turner C, Dalton N, Thomson A, Cochrane G M, Clark T J
Br J Clin Pharmacol. 1983 Oct;16(4):405-11. doi: 10.1111/j.1365-2125.1983.tb02185.x.
We studied the effect of posture on the sympathoadrenal response to intravenous theophylline in six normal subjects. On three separate occasions they received an intravenous infusion of either theophylline (6 mg/kg) while supine, theophylline (6 mg/kg) while standing or saline as placebo while standing. With the subjects standing theophylline caused tremor, a peak heart rate of 99 +/- 6 beats/min, and an elevation of plasma cyclic AMP from 9.3 +/- 0.7 to 15.1 +/- 1.7 nmol/1 (mean +/- s.e. mean). There was a small, but significant, elevation of plasma adrenaline, noradrenaline and glucose. The elevation in plasma catecholamines was insufficient to explain either the sympathomimetic effects of theophylline or the rise in plasma cyclic AMP. Theophylline had little or no effect with the subjects supine. The mean peak theophylline concentration following infusion was significantly higher with the subjects upright than when supine (18.3 c.f. 12.4 mg/l, P less than 0.025). However, adequate plasma levels of theophylline were obtained in all subjects when lying or supine. Analysis of individual data suggests that differences in plasma levels of theophylline are unlikely to account for the increased effects seen on standing. The mechanism of action of theophylline cannot be explained by increased secretion of catecholamines alone. Theophylline appears to amplify the increased sympathetic activity associated with standing and this is probably by phosphodiesterase inhibition.
我们研究了体位对6名正常受试者静脉注射茶碱后交感肾上腺反应的影响。在三个不同的场合,他们分别在仰卧位接受静脉输注茶碱(6mg/kg)、站立位接受茶碱(6mg/kg)或站立位接受生理盐水作为安慰剂。受试者站立时,茶碱会引起震颤,心率峰值为99±6次/分钟,血浆环磷酸腺苷从9.3±0.7升高至15.1±1.7nmol/1(平均值±标准误平均值)。血浆肾上腺素、去甲肾上腺素和葡萄糖有小幅但显著的升高。血浆儿茶酚胺的升高不足以解释茶碱的拟交感神经效应或血浆环磷酸腺苷的升高。受试者仰卧时,茶碱几乎没有效果。输注后茶碱的平均峰值浓度在受试者站立时显著高于仰卧时(18.3对比12.4mg/l,P<0.025)。然而,所有受试者在卧位或仰卧位时都获得了足够的茶碱血浆水平。对个体数据的分析表明,茶碱血浆水平的差异不太可能解释站立时观察到的增强效应。茶碱的作用机制不能仅用儿茶酚胺分泌增加来解释。茶碱似乎放大了与站立相关的交感神经活动增加,这可能是通过抑制磷酸二酯酶实现的。