Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle.
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.
Swissa
Moshe
M
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles 90048, USA.
Ohara
Toshihiko
T
Lee
Moon-Hyoung
MH
Kaul
Sanjay
S
Shah
Prediman K
PK
Hayashi
Hideki
H
Chen
Peng-Sheng
PS
Karagueuzian
Hrayr S
HS
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
D020030:Nitric Oxide Donors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate