ADENOSINE-SENSITIVE VENTRICULAR-TACHYCARDIA - EVIDENCE SUGGESTING CYCLIC-AMP MEDIATED TRIGGERED ACTIVITY
ADENOSINE-SENSITIVE VENTRICULAR-TACHYCARDIA - EVIDENCE SUGGESTING CYCLIC-AMP MEDIATED TRIGGERED ACTIVITY
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DOI：
10.1161/01.cir.74.2.270
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发表时间：
1986-08-01
期刊：
影响因子：
37.8
通讯作者：
DIMARCO, JP
中科院分区：
文献类型：
--
作者：
LERMAN, BB;BELARDINELLI, L;DIMARCO, JP
儿茶酚胺诱导的触发活性被认为是由细胞内cAMP（cAMP）升高介导的细胞内钙超载引起的。虽然在分离的制剂中显示发生，但缺乏支持其临床存在的证据。对4例结构正常的心脏患者进行了电生理研究，这些患者患有与劳力相关的持续性室性心动过速（VT）。程控刺激在所有患者中可重复启动和终止VT。通过输注异丙肾上腺素也可促进心动过速的诱导。腺苷是一种内源性核苷，其对心室肌和浦肯野纤维的唯一已知电生理作用是拮抗儿茶酚胺诱导的细胞内cAMP产生的刺激，可重复地终止所有VT发作。静脉注射维拉帕米和Valsalva手法和/或颈动脉窦按摩也终止了心动过速。β-肾上腺素能受体阻滞剂普萘洛尔终止或防止诱导VT在程序性刺激或儿茶酚胺挑战。在室性心动过速期间，14例心律失常符合折返标准的患者也接受了腺苷治疗，其中2例还患有运动诱发的室性心动过速。腺苷，在剂量（112.5至225 μ g/kg i. v.）足以在心室起搏期间引起窦性减慢/停搏或室房阻滞，但未能减缓或终止这些患者的任何VT发作。维拉帕米和自主神经调节在这组患者中也无效。腺苷、维拉帕米、迷走神经操作（乙酰胆碱）和β-肾上腺素能受体阻断剂都已知通过调节钙通道直接或通过抑制细胞cAMP的产生间接降低缓慢内向钙电流。因此，本研究中观察到，降低细胞内cAMP的干预措施可以终止或预防结构正常心脏和运动诱导的VT患者的VT诱导，这表明心动过速的机制可能是cAMP介导的触发活动。
Catecholamine-induced triggered activity is thought to be caused by intracellular calcium overload mediated by elevation of intracellular cyclic AMP (cAMP). Although shown to occur in isolated preparations, evidence supporting its clinical existence has been lacking. Electrophysiologic studies were performed in four patients with structurally normal hearts who had exertionally related sustained ventricular tachycardia (VT). Programmed stimulation reproducibly initiated and terminated VT in all patients. Induction of tachycardia was also facilitated by infusion of isoproterenol. Adenosine, an endogenous nucleoside, whose only known electrophysiologic effect on ventricular myocardium and Purkinje fibers is antagonism of catecholamine-induced stimulation of intracellular cAMP production, reproducibly terminated all episodes of VT. The tachycardia was also terminated by intravenous verapamil and by the Valsalva maneuver and/or carotid sinus massage. .beta.-Adrenergic receptor blockade with propranolol either terminated or prevented induction of VT during programmed stimulation or catecholamine challenge. Adenosine was also administered during VT to 14 patients whose arrhythmias fulfilled standard criteria for reentry, two of whom also had exercise-induced VT. Adenosine, at a dose (112.5 to 225 .mu.g/kg i.v.) sufficient to cause either sinus slowing/arrest or ventriculoatrial block during ventricular pacing, failed to slow or terminate any episode of VT in these patients. Verapamil and autonomic modulation were also ineffective in this group of patients. Adenosine, verapamil, vagal maneuvers (acetylcholine), and .beta.-adrenergic receptor blockade are all known to decrease the slow-inward calcium current either directly by modulating calcium channels or indirectly by inhibiting production of cellular cAMP. Therefore the observation in this study that interventions that lower intracellular cAMP either terminate or prevent induction of VT in patients with structurally normal hearts and exercise-induced VT suggests that the mechanism of tachycardia may be cAMP-mediated triggered activity.