Document Detail

Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle.
MedLine Citation:
PMID:  11959644     Owner:  NLM     Status:  MEDLINE    
We tested the hypothesis that sildenafil, singly or in combination with nitric oxide (NO) donors, promotes ventricular tachycardia (VT) and ventricular fibrillation (VF). Vulnerability to VT/VF was tested by rapid pacing in eight isolated normal swine right ventricles (RV). The endocardial activation was optically mapped, and the dynamic action potential duration (APD) restitution curves were constructed with metal microelectrodes. At baseline, no VT/VF could be induced. Sildenafil (0.2 microg/ml) or NO donor singly or in combination did not alter VT/VF vulnerability. However, when 2 microg/ml sildenafil was combined with NO donors, the incidence of VT and VF rose significantly (P < 0.01). VT with a single periodic wavefront was induced in five of eight RVs, and VF with multiple wavefronts was induced in all eight RVs. The sildenafil-NO donor pro-VT/VF combination significantly increased the maximum slope of the APD restitution curve and the amplitude of the APD alternans. The pro-VT/VF effects of sildenafil were reversible after drug-free Tyrode solution perfusion. We conclude that a sildenafil (2 microg/ml) and NO donor combination increases VT/VF vulnerability in the normal RV by a mechanism compatible with the restitution hypothesis.
Moshe Swissa; Toshihiko Ohara; Moon-Hyoung Lee; Sanjay Kaul; Prediman K Shah; Hideki Hayashi; Peng-Sheng Chen; Hrayr S Karagueuzian
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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:  American journal of physiology. Heart and circulatory physiology     Volume:  282     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-04-17     Completed Date:  2002-05-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1787-92     Citation Subset:  IM    
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles 90048, USA.
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MeSH Terms
Action Potentials
Nitric Oxide Donors / administration & dosage*,  adverse effects*
Piperazines / administration & dosage*,  adverse effects*
Tachycardia, Ventricular / chemically induced*
Ventricular Dysfunction, Right / chemically induced*
Ventricular Fibrillation / chemically induced
Grant Support
Reg. No./Substance:
0/Nitric Oxide Donors; 0/Piperazines; 0/Purines; 0/Sulfones; 139755-83-2/sildenafil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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