Cannom D S, Rider A K, Stinson E B, Harrison D C
Am J Cardiol. 1975 Dec;36(7):859-66. doi: 10.1016/0002-9149(75)90074-0.
Five patients who had received a transplanted human heart 1 to 3 years previously were studied to determine the effects of norepinephrine, isoproterenol and propranolol on the atrioventricular (A-V) conduction system. Using the His bundle technique, atrial, His bundle and ventricular electrograms were recorded, and central aortic pressure was monitored during the administration of these drugs. Norepinephrine was given by continuous infusion to four patients in doses ranging from 4 to 8 mug/min, with the systolic arterial pressure increasing by an average of 72 mm Hg. Concomitantly, there was an average increase in the rate of the donor atrium of 32 beats/min, and a reflex slowing of the recipient atrium of 23 beats/min. The A-H interval shortened by an average of 27 msec. Isoproterenol dose-response curves were performed in three patients, with the maximal dose being 5.2 mug by intravenous bolus infusion. The rate of the donor atrium increased by an average of 40 beats/min, and that of the recipient atrium by 18 beats/min. The A-H time shortened by an average of 25 msec, with a drop in systolic blood pressure averaging 23 mm Hg. Propranolol (7 mg intravenously) was given to three patients and the peak doses of norepinephrine and isoproterenol were again infused. Beta adrenergic blockade was achieved at this dose of propranolol since there was only a minimal increase in the donor atrial rate after infusion of the drug. The A-H interval was not altered by catecholamine infusion after achievement of beta blockade. However, the levels of systolic hypertension noted after infusion of norepinephrine was not altered by propranolol. The denervated transplanted human heart appears to respond normally to norepinephrine and isoproterenol, and the electrophysiologic effects of these agents are blocked by propranolol. Extensive investigative work in the denervated canine model has demonstrated the presence of the alpha and beta cardiovascular receptors. Although the automonic nervous system is important in cardiac performance, this work is the first validation in man that (1) the functional integrity of the beta receptor is maintained even when the autonomic nerves are absent, and (2) the intrinsic properties of the sinus and atrioventricular nodes are the keystone in stabilizing cardiac electrophysiology after denervation.
对5例在1至3年前接受过人类心脏移植的患者进行了研究，以确定去甲肾上腺素、异丙肾上腺素和普萘洛尔对房室（A-V）传导系统的影响。采用希氏束技术，记录心房、希氏束和心室电图，并在给予这些药物期间监测中心主动脉压。对4例患者持续输注去甲肾上腺素，剂量范围为4至8微克/分钟，收缩期动脉压平均升高72毫米汞柱。与此同时，供体心房率平均增加32次/分钟，受体心房反射性减慢23次/分钟。A-H间期平均缩短27毫秒。对3例患者进行了异丙肾上腺素剂量反应曲线研究，静脉推注最大剂量为5.2微克。供体心房率平均增加40次/分钟，受体心房率增加18次/分钟。A-H时间平均缩短25毫秒，收缩压平均下降23毫米汞柱。对3例患者给予普萘洛尔（静脉注射7毫克），然后再次输注去甲肾上腺素和异丙肾上腺素的峰值剂量。给予该剂量的普萘洛尔可实现β肾上腺素能阻滞，因为输注该药物后供体心房率仅略有增加。实现β阻滞后，儿茶酚胺输注未改变A-H间期。然而，普萘洛尔并未改变输注去甲肾上腺素后出现的收缩期高血压水平。去神经支配的移植人类心脏似乎对去甲肾上腺素和异丙肾上腺素反应正常，普萘洛尔可阻断这些药物的电生理效应。在去神经支配的犬模型中进行的大量研究工作已证明存在α和β心血管受体。尽管自主神经系统对心脏功能很重要，但这项工作是首次在人体中证实：（1）即使自主神经缺失，β受体的功能完整性仍得以维持；（2）窦房结和房室结的固有特性是去神经支配后稳定心脏电生理的关键。
