Central and peripheral effects of dexmedetomidine on autonomic cardiovascular regulation

右美托咪定是一种中枢作用的α 2-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，但偶尔会观察到严重的心动过缓和窦性骤停。本研究的目的是检查对心脏的直接作用（外周作用）或中枢迷走神经激活是美托咪定副作用的原因。为了评价迷走神经的传出活性，我们通过将微透析纤维植入麻醉兔的心肌间质来测量乙酰胆碱。静脉给药美托咪定增加心肌间质乙酰胆碱浓度，迷走神经切开术使其消失。这些结果表明，美托咪定中枢激活迷走神经，可引起心动过缓，在严重的情况下，窦性停搏。

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.