Gantenberg N S, Hageman G R
Department of Physiology and Biophysics, University of Alabama, Birmingham 35294.
Can J Physiol Pharmacol. 1992 Feb;70(2):240-6. doi: 10.1139/y92-030.
Cocaine abuse increases the susceptibility to cardiovascular complications and sudden cardiac death in man. We used programmed electrical stimulation of the heart to examine the arrhythmogenic influence of cocaine. Twenty-three pentobarbital-anesthetized adult dogs underwent programmed electrical stimulation using one to four extrastimuli before and during cocaine infusion. Autonomic decentralization was performed prior to the protocol in eight dogs. Induced ventricular arrhythmias included single premature ventricular depolarizations, doublets, triplets, ventricular tachycardia, and ventricular fibrillation. Intravenous cocaine, and subsequent adrenergic and muscarinic receptor blockade, or calcium channel blockade were evaluated for their influence on arrhythmogenesis. The incidence of induced ventricular arrhythmias was significantly elevated following cocaine and was reduced following propranolol and atropine. Verapamil, however, did not reduce the incidence of induced arrhythmias. In addition, cocaine significantly increased arrhythmia induction in decentralized animals, but propranolol, atropine, and phentolamine failed to reduce the proarrhythmic effects of cocaine in these animals. Thus, cocaine has a proarrhythmic effect on the heart with multiple mechanisms. The adrenergic mechanism appears to be a result of neurotransmitter uptake blockade, whereas the likely ionic mechanism is a neurally independent, direct effect on the heart.
可卡因滥用会增加人类发生心血管并发症和心源性猝死的易感性。我们使用心脏程序性电刺激来研究可卡因的致心律失常作用。23只戊巴比妥麻醉的成年犬在输注可卡因之前和期间，使用1至4个额外刺激进行程序性电刺激。在实验方案实施前，对8只犬进行了自主神经去传入。诱发的室性心律失常包括单个室性早搏去极化、成对早搏、三联律、室性心动过速和心室颤动。评估静脉注射可卡因以及随后的肾上腺素能和毒蕈碱受体阻断或钙通道阻断对心律失常发生的影响。可卡因注射后诱发的室性心律失常发生率显著升高，而普萘洛尔和阿托品注射后发生率降低。然而，维拉帕米并未降低诱发心律失常的发生率。此外，可卡因显著增加了去传入动物的心律失常诱发率，但普萘洛尔、阿托品和酚妥拉明未能降低这些动物中可卡因的促心律失常作用。因此，可卡因通过多种机制对心脏产生促心律失常作用。肾上腺素能机制似乎是神经递质摄取阻断的结果，而可能的离子机制是一种与神经无关的对心脏的直接作用。
