Lejeune P, Naeije R
Laboratory of Cardiovascular and Respiratory Physiology, Erasmus University Hospital, Brussels, Belgium.
Arch Int Pharmacodyn Ther. 1988 Jul-Aug;294:215-27.
We investigated the effects of progressively increased i.v. doses of theophylline and of the newly introduced methylxanthine derivative S 9795 on hemodynamics, blood gases and lung mechanics in 2 groups each of 8 pentobarbital sodium-anesthetized dogs. The maximum plasma levels that were attained were 56.6 +/- 3.4 micrograms/ml (mean +/- S.E.) for theophylline and 12 +/- 1.2 micrograms/ml for S 9795. Theophylline increased heart rate and cardiac output, decreased arterial PO2, increased O2 consumption and did not affect lung mechanics. S 9795 decreased heart rate, increased systemic arterial pressure, O2 consumption (slightly) and pulmonary capillary wedge pressure (the latter only at the highest dose) and decreased lung compliance without change in lung resistance. The evolutions of heart rate, O2 consumption and pulmonary capillary wedge pressure differed significantly after theophylline compared to S 9795. These results show that in dogs, theophylline acts as a positive chronotrope, while S 9795 either has no such effect or acts as a negative chronotrope at high doses. None of the 2 methylxanthines appears to reduce normal bronchomotor tone.
我们研究了静脉注射剂量逐渐增加的茶碱以及新引入的甲基黄嘌呤衍生物S 9795对两组各8只戊巴比妥钠麻醉犬的血流动力学、血气和肺力学的影响。茶碱达到的最大血浆水平为56.6±3.4微克/毫升(平均值±标准误),S 9795为12±1.2微克/毫升。茶碱可增加心率和心输出量,降低动脉血氧分压,增加氧耗量,且不影响肺力学。S 9795可降低心率,增加体循环动脉压、氧耗量(略有增加)和肺毛细血管楔压(仅在最高剂量时),并降低肺顺应性,而肺阻力无变化。与S 9795相比,茶碱给药后心率、氧耗量和肺毛细血管楔压的变化有显著差异。这些结果表明,在犬中,茶碱起正性变时作用,而S 9795要么无此作用,要么在高剂量时起负性变时作用。这两种甲基黄嘌呤似乎都不能降低正常支气管运动张力。