Covert R F, Drummond W H
Department of Pediatrics, University of Chicago, IL 60637.
Biol Neonate. 1994;66(6):316-23. doi: 10.1159/000244124.
alpha-Chloralose is a commonly used anesthetic agent in cardiovascular research despite a paucity of information whether it may have important pharmacologic interaction with subsequently given adrenergic drugs. To assess any potential pharmacologic interaction, we studied the cardiovascular response to beta-adrenergic receptor antagonism (propranolol, 1 mg/kg i.v.) after either chloralose (30 mg/kg i.v.) or saline control in paired studies in 10 chronically instrumented neonatal lambs. Chloralose increased heart rate by 46% as compared to control (283 +/- 37 vs. 194 +/- 48 beats/min, p = 0.0002) and had no significant effect on cardiac output; chloralose also increased mean pulmonary arterial pressure by 45% (27 +/- 13 vs. 19 +/- 6 mm Hg, p = 0.050) and pulmonary vascular resistance by 79% (0.211 +/- 0.13 vs. 0.118 +/- 0.04 mm Hg/ml/kg/min, p = 0.050). The group pretreated with chloralose had significantly elevated heart rate (186 +/- 23 vs. 157 +/- 31 beats/min, p = 0.03), mean pulmonary arterial pressure (29 +/- 9 vs. 22 +/- 6 mm Hg, p = 0.03) and pulmonary vascular resistance (0.228 +/- 0.13 vs. 0.130 +/- 0.05 mm Hg/ml/kg/min, p = 0.05) after propranolol as compared to the conscious saline-treated group. We conclude that pretreatment with chloralose as an anesthetic agent may produce important pharmacologic interaction with subsequent adrenergic drugs in neonatal lambs. While anesthesia may be necessary in animal research, investigators should be aware that the anesthetic agent may also qualitatively and quantitatively influence measured outcome variables.
尽管关于α-氯醛糖与随后给予的肾上腺素能药物是否可能存在重要的药物相互作用的信息匮乏,但它仍是心血管研究中常用的麻醉剂。为了评估任何潜在的药物相互作用,我们在10只长期植入仪器的新生羔羊的配对研究中,研究了在给予氯醛糖(30mg/kg静脉注射)或生理盐水对照后,β-肾上腺素能受体拮抗(普萘洛尔,1mg/kg静脉注射)对心血管的反应。与对照组相比,氯醛糖使心率增加了46%(分别为283±37次/分钟和194±48次/分钟,p = 0.0002),对心输出量无显著影响;氯醛糖还使平均肺动脉压增加了45%(分别为27±13mmHg和19±6mmHg,p = 0.050),肺血管阻力增加了79%(分别为0.211±0.13和0.118±0.04mmHg/ml/kg/min,p = 0.050)。与清醒的生理盐水处理组相比,预先用氯醛糖处理的组在给予普萘洛尔后心率(分别为186±23次/分钟和157±31次/分钟,p = 0.03)、平均肺动脉压(分别为29±9mmHg和22±6mmHg,p = 0.03)和肺血管阻力(分别为0.228±0.13和0.130±0.05mmHg/ml/kg/min,p = 0.05)显著升高。我们得出结论,在新生羔羊中,预先使用氯醛糖作为麻醉剂可能会与随后的肾上腺素能药物产生重要的药物相互作用。虽然在动物研究中麻醉可能是必要的,但研究人员应该意识到麻醉剂也可能在质量和数量上影响所测量的结果变量。