Pace D G, Gillis R A
J Pharmacol Exp Ther. 1976 Dec;199(3):583-600.
The effect of intravenous injections of digoxin (20 mug/kg every 15 minutes) on spontaneously occurring activity in autonomic efferent nerves, motor nerves, afferent nerves, electrocardiogram and on arterial blood pressure was evaluated in chloralose-anesthetized cats. Administration of digoxin enhanced neural activity in pre- and postganglionic cardiac synpathetic nerves and this enhancement occurred near the time the disturbances in ventricular rhym were noted. Neural activity continued to increase during ventricular tachycardia and maximum enhancement was observed just proir to ventricular fibrillation. Similar results were observed when digoxin was administered to animals in which neural activity was recorded from preganglionic splanchnic and superior cervical nerves. Digoxin administration also increased discharge frequency from vagus (efferent fibers), phrenic and carotid sinus nerves. Denervation of cardiovascular reflexogenic areas prevented the increased discharge in vagus nerves, reduced it in phrenic nerves, but did not affect nerve discharge in sympathetic nerves. These results suggest that digoxin-induced hyperactivity in synpathetic nerves was related to a central nervous system effect of the drug, whereas the mechanism for the digoxin-induced hyperactivity in vagus nerves involved a peripheral reflex effect of the drug. Both sites were involved in the digoxin-induced hyperactivity in phrenic nerves. Enhancement of cardiac sympathetic nerve activity appeared to be responsible for the ventricular arrhythmias provoked by digoxin as 1) a temporal relationship was observed between augmented nerve activity and arrhythmia development, 2) a centrally acting sympathetic nervous system depressant drug, clonidine, converted the ventricular arrhythmia to normal rhythm, and 3) removal of sympathetic influence to the heart by spinal cord transection decreased the sensitivity of the heart to the arrhythmogenic effect of digoxin. These results suggest that digoxin partially responsible for its cardiotoxic effects.
在水合氯醛麻醉的猫身上，评估了静脉注射地高辛（每15分钟20微克/千克）对自主传出神经、运动神经、传入神经的自发活动、心电图以及动脉血压的影响。给予地高辛增强了节前和节后心脏交感神经的神经活动，这种增强在注意到心室节律紊乱的时间附近出现。在室性心动过速期间神经活动持续增加，在心室颤动之前观察到最大增强。当给从节前内脏神经和颈上神经记录神经活动的动物注射地高辛时，观察到了类似的结果。给予地高辛还增加了迷走神经（传出纤维）、膈神经和颈动脉窦神经的放电频率。去除心血管反射发生区的神经支配可防止迷走神经放电增加，使膈神经放电减少，但不影响交感神经的神经放电。这些结果表明，地高辛引起的交感神经活动亢进与药物的中枢神经系统效应有关，而地高辛引起的迷走神经活动亢进的机制涉及药物的外周反射效应。膈神经中地高辛引起的活动亢进涉及这两个部位。心脏交感神经活动增强似乎是地高辛诱发室性心律失常的原因，因为1）观察到神经活动增强与心律失常发生之间存在时间关系，2）一种中枢作用的交感神经系统抑制药物可乐定可将室性心律失常转为正常节律，3）脊髓横断去除心脏的交感神经影响可降低心脏对地高辛致心律失常作用的敏感性。这些结果表明，地高辛对其心脏毒性作用负有部分责任。
