Central and peripheral effects of dexmedetomidine on autonomic cardiovascular regulation

右美托咪定是一种中枢作用的α2-肾上腺素能激动剂，用于重症监护病房的镇静。虽然它对呼吸功能的影响很小，但偶尔也会观察到严重的心动过缓和窦性停搏。本研究的目的是研究美托咪定对心脏的直接影响(外周效应)或中枢迷走神经兴奋中的哪一种是导致这些副作用的原因。为了评价迷走神经传出活动，通过植入麻醉兔心肌间质的微透析纤维来测量乙酰胆碱。静脉注射美多咪定可增加心肌间质乙酰胆碱浓度，但这种作用可被迷走神经切断术取消。这些结果表明，美地咪定中枢激活迷走神经，可能导致心动过缓，在严重情况下，还会导致窦性心搏骤停。

Dexmedetomidine is a centrally acting alpha2-adrenergic agonist and is used for sedation in the intensive care units. Although it has a minimal effect on respiratory function, severe bradycardia and sinus arrest are occasionally observed. The aim of the present study was to examine which of the direct effect on the heart (peripheral effect) or the central vagal activation is responsible for such side effects of medetomidine. To evaluate efferent vagal activity, acetylcholine was measured through a microdialysis fiber implanted into the myocardial interstitium of anesthetized rabbits. Intravenous medetomidine administration increased myocardial interstitial acetylcholine concentration, which was abolished by vagotomy. These results indicate that medetomidine centrally activates the vagal nerve and can cause bradycardia and, in severe cases, sinus arrest.