These data demonstrate that ibutilide is able to rapidly terminate atrial fibrillation and atrial flutter.

The effects of adenosine on the human His-Purkinje system (HPS) were studied in nine patients with complete atrioventricular (AV) block. Adenosine had minimal effect on the control HPS cycle length, but in the presence of isoproterenol increased it from 906±183 to 1,449±350 ms, P < 0.001. Aminophylline, a competitive adenosine antagonist, completely abolished this antiadrenergic effect of adenosine.In isolated guinea pig hearts with surgically induced AV block, isoproterenol decreased the HPS rate by 36%, whereas in the presence of 1,3-dipropyl-8-phenyl-xanthine, a potent adenosine antagonist, the HPS rate decreased by 48% and was associated with an increased release of adenosine. Therefore, by blocking the effects of adenosine at the receptor level, the physiologic negative feedback mechanism by which adenosine antagonizes the effects of catecholamines was uncoupled.The results of this study indicate that adenosine's effects on the human HPS are primarily antiadrenergic and are thus consistent with the concept of accentuated antagonism. These effects of adenosine may serve as a counterregulatory metabolic response that improves the 02 supply-demand ratio perturbed by enhanced sympathetic tone. Some catecholaminemediated ventricular arrhythmias that occur during ischemia or enhanced adrenergic stress may be due to an imbalance in this negative feedback system.

Mechanisms responsible for atrioventricular (AV) block during acute inferior myocardial infarction are only partially understood. Increased parasympathetic tone is the factor usually postulated; however, persistence of AV block after atropine administration is frequently observed. Adenosine, an endogenous ischemic metabolite, has well established depressant effects on AV node conduction. In this report, an episode of atropine-resistant AV block was reversed by aminophylline, a competitive adenosine antagonist, in a patient with an acute inferior myocardial infarction. This observation suggests a role for adenosine in the mediation of ischemia-induced AV node block.

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Exogenous adenosine has been shown to have potent electrophysiologic effects and antiarrhythmic properties within the atrioventricular (AV) node. Endogenous adenosine, a nucleoside with an increased release signaled by ischemia and hypoxia, is not believed to exert significant effects during homeostatic conditions. Recent experimental evidence suggests, however, that under normoxic conditions, the amount of adenosine released may be sufficient to mediate some of its physiologic effects. This study was designed to test the hypothesis that in humans the electrophysiologic effects of endogenously released adenosine on AV nodal conduction can be demonstrated under normoxic conditions by inhibiting uptake and degradation of the nucleoside. In the first protocol, the effects of intravenous dipyridamole (0.56 mg/kg bolus i.v., 5 ,ug/kg/minute infusion), a nucleoside-transport blocker that elevates endogenous plasma levels of adenosine, on AV nodal conduction were evaluated in seven patients. At a constant atrial paced cycle length, dipyridamole increased the AH interval from 110±+19 to 164+26 msec, p=0.002 (+SEM). Aminophylline (5.6 mg/kg i.v.), a competitive antagonist of adenosine, completely reversed the effects of dipyridamole on AV nodal conduction. Similarly, dipyridamole increased the cycle length at which pacing-induced AV nodal Wenckebach occurred, from 348±31 (control) to 388±33 msec (dipyridamole) (p=0.002). In a second protocol, the effects of intravenous dipyridamole were evaluated in another group of six patients who had supraventricular tachycardia (SVT) in which the AV node was part of the reentrant circuit. Dipyridamole increased the cycle length of SVT from 344 ±29 to 379+ 30 msec (p<0.05), effects that were confined primarily to the AV node (AH interval). Dipyridamoie alone terminated SVT (and prevented reinduction) in one of six patients. In the remaining five patients, dipyridamole reduced fourfold the minimum-efective dose of exogenous adenosine required to terminate SVT, that is, from 68±15 to 17+6 ,ug/kg (p=0.005). These results show that the electrophysiologic and antiarrhythmic properties of endogenous adenosine on the AV node may be demonstrated in the absence of ischemia by attenuating nucleoside transport and degradation. Although the elfects of dipyridamole during SVT were modest, the results of this study suggest that the development of more potent and specific nucleoside-transport blockers that elevate endogenous adenosine levels may provide an elfective therapeutic modality in patients with SVT. (Circulation 1989;80:1536-1543 A denosine is a unique endogenous nucleoside adenosine A1 receptor to K' channels by a guaninewith potent, site-specific electrophysiologic nucleotide-regulatory binding protein, Gk3'4 (although effects and antiarrhythmic properties within an effect on calcium channels has not been entirely the atrioventricular (AV) node.1'2 Similar to its action ruled out). Activation of K' channels by adenosine, in atrial myocytes, adenosine is believed to mediate which hyperpola...

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