title: Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle.
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 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.
authors.affiliation: Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles 90048, USA.
authors.forename: Moshe
authors.initials: M
authors.lastname: Swissa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ohara
authors.forename: Moon-Hyoung
authors.initials: MH
authors.lastname: Lee
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kaul
authors.forename: Prediman K
authors.initials: PK
authors.lastname: Shah
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
authors.forename: Hrayr S
authors.initials: HS
authors.lastname: Karagueuzian
mesh_terms: D000200:Action Potentials; D000818:Animals; D005260:Female; D008297:Male; D020030:Nitric Oxide Donors / Q000008:administration & dosage* / Q000009:adverse effects*; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D013552:Swine; D017180:Tachycardia, Ventricular / Q000139:chemically induced*; D018497:Ventricular Dysfunction, Right / Q000139:chemically induced*; D014693:Ventricular Fibrillation / Q000139:chemically induced
chemical_list: D020030:Nitric Oxide Donors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate