Penttilä Jani, Helminen Antti, Anttila Markku, Hinkka Susanna, Scheinin Harry
Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.
Can J Physiol Pharmacol. 2004 May;82(5):359-62. doi: 10.1139/y04-028.
We evaluated the cardiovascular effects of intravenously (i.v.) and buccally administered dexmedetomidine, a selective alpha2-adrenoceptor agonist. Six healthy male subjects were studied unmedicated and after 2 micro g/kg i.v. or buccal doses of dexmedetomidine, using repeated recordings of ECG and blood pressure. Cardiac parasympathetic activity was estimated by measurements of high-frequency (HF) heart rate variability. Intravenous, but not buccal, dexmedetomidine raised systolic blood pressure by 11 +/- 5 mmHg (mean +/- SEM) and diastolic by 16 +/- 3 mmHg (maxima at 10 min). Later on, both i.v., and buccal dexmedetomidine produced a very similar hypotensive effect: on average, >or=10 mmHg reductions in systolic and diastolic pressure at 3 h. Intravenous dosing was followed by a decline in heart rate (-11 +/- 2 beats/min) accompanied by a trend toward enhanced HF variability (maximal effect at 10 min), which probably reflected baroreflex-mediated parasympathetic efferent neuronal activation. Buccal dexmedetomidine increased significantly the HF variability (maximum at 45 min) without influencing heart rate. We conclude that dexmedetomidine, when administered by a method that avoids concentration peaks, e.g., buccal dosing, can be used to produce a prolonged augmentation of cardiac parasympathetic efferent neuronal activity.
我们评估了静脉注射(i.v.)和经颊给药的右美托咪定(一种选择性α2肾上腺素能受体激动剂)对心血管系统的影响。对6名健康男性受试者在未用药时以及静脉注射2μg/kg或经颊给予右美托咪定后进行了研究,采用重复记录心电图和血压的方法。通过测量高频(HF)心率变异性来评估心脏副交感神经活动。静脉注射而非经颊给药的右美托咪定使收缩压升高11±5 mmHg(平均值±标准误),舒张压升高16±3 mmHg(10分钟时达到最大值)。随后,静脉注射和经颊给药的右美托咪定均产生了非常相似的降压效果:平均而言,3小时时收缩压和舒张压降低≥10 mmHg。静脉给药后心率下降(-11±2次/分钟),同时高频变异性有增强趋势(10分钟时达到最大效应),这可能反映了压力反射介导的副交感传出神经元激活。经颊给予右美托咪定显著增加了高频变异性(45分钟时达到最大值),但不影响心率。我们得出结论,当通过避免浓度峰值的方法给药时,例如经颊给药,右美托咪定可用于延长心脏副交感传出神经元活动的增强。