Antiadrenergic effects of adenosine on His-Purkinje automaticity. Evidence for accentuated antagonism.

Lerman, Bruce B.; Wesley, Robert C.; DiMarco, John P.; Haines, David E.; Belardinelli, Luiz

doi:10.1172/jci113834

Cited by 72 publications

(34 citation statements)

References 67 publications

(85 reference statements)

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“…Of the 49 focal ATs, 17 were due to microreentry, 26 to triggered activity, and 6 were due to enhanced automaticity. Patients with focal AT were younger (59 years, 54-64) versus those with macroreentry (68 years, 64-74; P=0.018) and less likely to have structural heart disease (17 . Among focal ATs, microreentrant tachycardia was less likely to be catecholamine-dependent (P=0.041) and was more likely to be associated with previous ablation (P=0.041) originating at a previous site of ablation in 6/11 patients (Table 2).…”

Section: Patient Characteristics (Focal Versus Macroreentry)mentioning

confidence: 99%

“…4,[16][17][18][19][20] Adenosine's actions in ventricular tachycardia are mechanism-specific, terminating only ventricular tachycardia due to delayed afterdepolarization-mediated triggered activity and having no effect in macroreentrant or microreentrant ventricular tachycardia. 21 Based on the results of this study, the specificity of adenosine's mechanistic effects seems to be generalizable for any sustained monomorphic tachycardia, whether originating from the atria or ventricles.…”

Section: Algorithm and Clinical Implicationsmentioning

confidence: 99%

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Unifying Algorithm for Mechanistic Diagnosis of Atrial Tachycardia

Liu

Cheung

et al. 2016

Circ: Arrhythmia and Electrophysiology

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Background-No existing criteria unequivocally differentiate focal atrial tachycardia (AT) caused by microreentry, triggered activity, or enhanced automaticity. Although macroreentrant AT is readily diagnosed based on entrainment criteria, the smaller circuit dimension associated with microreentrant AT makes it challenging to validate the presence of reset with fusion. An algorithm was, therefore, developed that is independent of entrainment but which reliably identifies specific mechanisms of focal AT. Methods and Results-Fifty-nine patients with AT underwent adenosine testing after mapping of tacycardia. Ten ATs had nonfocal activation, with ≥90% of tachycardia cycle length identified with electroanatomical mapping, findings consistent with macroreenty. All ATs were insensitive to adenosine. Forty-nine patients had focal AT with centrifugal activation. In 32/49 (67%) ATs, electrograms were nonfractionated, and <50% of tachycardia cycle length could be mapped. Based on programmed stimulation, 26/32 (81%) of these ATs were classified as due to triggered activity and 6/32 (19%) as due to enhanced automaticity. Adenosine terminated 100% of triggered ATs and transiently slowed or suppressed 100% of automatic ATs. The remaining 17 focal ATs had localized fractionated electrograms (≥35% of tachycardia cycle length) at the site of successful ablation and were classified as microreentrant. Adenosine had no effect in these ATs. The response to adenosine accurately differentiated all subtypes of focal AT, P<0.05. Conclusions-Adenosine-sensitivity (termination or transient slowing/suppression) in response to adenosine was 100% sensitive and specific for identifying focal AT mechanisms due to triggered activity or automaticity, respectively. Absence of adenosine effect on focal AT identifies tachycardia due to microreentry. Methods Study PopulationWe studied 59 consecutive patients who presented for invasive electrophysiological evaluation and catheter ablation of AT and received adenosine during tachycardia. The presence of structural heart disease was based on a diagnosis of cardiomyopathy, valvular disease, coronary artery disease (> 60% stenosis), or prior myocardial infarction. All procedures were performed after informed consent was obtained for a study approved by the Institutional Review Board of Weill Cornell Medical College. Baseline Electrophysiology StudyAll patients underwent electrophysiology study in a postabsorptive state. Antiarrhythmic drugs were held for 5 half-lives before the study. Quadripolar catheters were positioned at the His bundle position and right ventricular apex. Right atrial electrogram recordings were obtained with either a quadripolar catheter positioned in the high right atrium or a 7-Fr duodecapolar catheter positioned along the tricuspid annulus. A 6-Fr decapolar catheter was positioned in the coronary sinus to record left atrial and left ventricular activity. In selected patients, a 5-spline mapping catheter configured as radial spokes was deployed (PentaRay Nav; Biosense-Webster, Dia...

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Section: Patient Characteristics (Focal Versus Macroreentry)mentioning

confidence: 99%

Section: Algorithm and Clinical Implicationsmentioning

confidence: 99%

Unifying Algorithm for Mechanistic Diagnosis of Atrial Tachycardia

Liu

Cheung

et al. 2016

Circ: Arrhythmia and Electrophysiology

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“…This form of tachycardia typically terminates in response to perturbations that lower stimulated levels of intracellular calcium, i. e., adenosine, verapamil, and enhanced vagal tone (2)(3)(4). Termination of idiopathic VT in response to adenosine is thought to be diagnostic of a cAMP-dependent mechanism since the ventricular electrophysiologic effects of adenosine are mediated through the inhibitory G protein G i , which inhibits adenylyl cyclase and decreases intracellular cAMP (5)(6)(7).…”

Section: Idiopathic Ventricular Tachycardia (Vt)mentioning

confidence: 99%

Right ventricular outflow tract tachycardia due to a somatic cell mutation in G protein subunitalphai2.

Lerman¹,

Dong²,

Steín³

et al. 1998

J. Clin. Invest.

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Idiopathic ventricular tachycardia is a generic term that describes the various forms of ventricular arrhythmias that occur in patients without structural heart disease and in the absence of the long QT syndrome. Many of these tachycardias are focal in origin, localize to the right ventricular outflow tract (RVOT), terminate in response to ␤ blockers, verapamil, vagal maneuvers, and adenosine, and are thought to result from cAMP-mediated triggered activity. DNA was prepared from biopsy samples obtained from myocardial tissue from a patient with adenosine-insensitive idiopathic ventricular tachycardia arising from the RVOT. Genomic sequences of the inhibitory G protein G ␣ i2 were determined after amplification by PCR and subcloning. A point mutation (F200L) in the GTP binding domain of the inhibitory G protein G ␣ i2 was identified in a biopsy sample from the arrhythmogenic focus. This mutation was shown to increase intracellular cAMP concentration and inhibit suppression of cAMP by adenosine. No mutations were detected in G ␣ i2 sequences from myocardial tissue sampled from regions remote from the origin of tachycardia, or from peripheral lymphocytes. These findings suggest that somatic cell mutations in the cAMP-dependent signal transduction pathway occurring during myocardial development may be responsible for some forms of idiopathic ventricular tachycardia. ( J.

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“…Dipyridamoie alone terminated SVT (and prevented reinduction) Adenosine production is increased in response to ischemia and hypoxia and functions to restore a physiologic 02 supply-demand ratio.7,8 For instance, increased adenosine release during myocardial hypoxia improves 02 supply by coronary vasodilation8 and decreases 02 demand by precipitating sinus bradycardia,9 AV block,10 and antagonizing the effects of sympathomimetic amines." [1][2][3][4][5][6][7][8][9][10][11][12][13] The electrophysiologic effects of adenosine have been primarily demonstrated by administering an exogenous preparation of the nucleoside because endogenous adenosine is not believed to be produced in sufficient amounts to have significant effects during normoxic conditions.1415 Recent evidence from studies in guinea pigs, however, suggests the contrary, that is, endogenous adenosine may have some physiologic role under normoxic conditions. 16 The purpose of this study was ProtocolA.…”

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confidence: 99%

Electrophysiologic effects of dipyridamole on atrioventricular nodal conduction and supraventricular tachycardia. Role of endogenous adenosine.

1989

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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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Antiadrenergic effects of adenosine on His-Purkinje automaticity. Evidence for accentuated antagonism.

Cited by 72 publications

References 67 publications

Unifying Algorithm for Mechanistic Diagnosis of Atrial Tachycardia

Unifying Algorithm for Mechanistic Diagnosis of Atrial Tachycardia

Right ventricular outflow tract tachycardia due to a somatic cell mutation in G protein subunitalphai2.

Electrophysiologic effects of dipyridamole on atrioventricular nodal conduction and supraventricular tachycardia. Role of endogenous adenosine.

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