Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle

Moshe Swissa, Toshihiko Ohara, Moon Hyoung Lee, Sanjay Kaul, Prediman K. Shah, Hideki Hayashi, Peng Sheng Chen, Hrayr S. Karagueuzian

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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 μg/ml) or NO donor singly or in combination did not alter VT/VF vulnerability. However, when 2 μg/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 μg/ml) and NO donor combination increases VT/VF vulnerability in the normal RV by a mechanism compatible with the restitution hypothesis.

Original languageEnglish (US)
Pages (from-to)H1787-H1792
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume282
Issue number5 51-5
StatePublished - Jun 29 2002
Externally publishedYes

Keywords

  • Electrical stimulation
  • Ventricular fibrillation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Swissa, M., Ohara, T., Lee, M. H., Kaul, S., Shah, P. K., Hayashi, H., Chen, P. S., & Karagueuzian, H. S. (2002). Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle. American Journal of Physiology - Heart and Circulatory Physiology, 282(5 51-5), H1787-H1792.