Document Detail

Mechanism of repetitive monomorphic ventricular tachycardia.
MedLine Citation:
PMID:  7634458     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The most common form of idiopathic ventricular tachycardia (VT) is repetitive monomorphic VT (RMVT), which is characterized by frequent ventricular ectopy and salvos of nonsustained VT with intervening sinus rhythm. Unlike most other forms of idiopathic VT, this tachycardia typically occurs at rest and is nonsustained. The mechanism of RMVT is undefined. Because of a common site of origin, the right ventricular outflow tract (RVOT), we hypothesized that RMVT is mechanistically related to paroxysmal sustained, exercise-induced VT, which has been shown to be consistent with cAMP-mediated triggered activity. Therefore, in this study, we sought to identify (1) the mechanism of RMVT at the cellular level by using electropharmacological probes known to activate either stimulatory or inhibitory G proteins and thereby modify intracellular cAMP levels, (2) potential autonomic triggers of RMVT through analysis of heart rate variability, and (3) whether well-characterized somatic activating mutations in the stimulatory G protein, G alpha s, underlie RMVT. METHODS AND RESULTS: Twelve patients with RMVT underwent electrophysiological study. Sustained monomorphic VT was reproducibly initiated and terminated with programmed stimulation and/or isoproterenol infusion in 11 of the 12 patients (the other patient had incessant RMVT). Induction of VT demonstrated cycle length dependence and was facilitated by rapid atrial or ventricular pacing. Termination of VT occurred in response to interventions that either lowered stimulated levels of intracellular cAMP (and thus decreased intracellular Ca2+)--ie, adenosine (12 of 12), vagal maneuvers or edrophonium (8 of 9), and beta-blockade (3 of 5)--or directly decreased the slow-inward calcium current--ie, verapamil (10 of 12). Analysis of heart rate variability during 24-hour ambulatory monitoring in 7 patients showed that the sinus heart rate is increased and accelerates before nonsustained VT (P < .05), whereas high-frequency heart rate variability is unchanged. These findings are consistent with transient increases in sympathetic tone preceding nonsustained VT. Finally, myocardial biopsy samples were obtained from the site of origin of the VT (typically the RVOT) and from the right ventricular apex from 9 patients. Genomic DNA was extracted from each biopsy sample, and three exons of G alpha s in which activating mutations have previously been described were amplified by polymerase chain reaction. All sequences from these regions were found to be identical to that of control. CONCLUSIONS: Although the arrhythmia occurs at rest, the constellation of findings in idiopathic VT that is characterized by RMVT is consistent with the mechanism of cAMP-mediated triggered activity. Therefore, the spectrum of VT resulting from this mechanism includes not only paroxysmal exercise-induced VT but also RMVT.
B B Lerman; K Stein; E D Engelstein; D S Battleman; N Lippman; D Bei; D Catanzaro
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  92     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-09-12     Completed Date:  1995-09-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  421-9     Citation Subset:  AIM; IM    
Department of Medicine, New York Hospital-Cornell Medical Center, NY 10021, USA.
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MeSH Terms
Adenosine / administration & dosage
Base Sequence
Catheter Ablation
Cyclic AMP / metabolism
Edrophonium / administration & dosage
GTP-Binding Proteins / biosynthesis,  genetics
Heart Rate
Middle Aged
Molecular Sequence Data
Polymerase Chain Reaction
Tachycardia, Ventricular / metabolism,  physiopathology*,  therapy
Grant Support
R01 44747//PHS HHS
Reg. No./Substance:
312-48-1/Edrophonium; 58-61-7/Adenosine; 60-92-4/Cyclic AMP; EC 3.6.1.-/GTP-Binding Proteins

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