Effects of combined sildenafil-nitric oxide donor on defibrillation efficacy.
BACKGROUND
A previous study demonstrated that supra-therapeutic concentration of sildenafil citrate attenuates defibrillation efficacy. However, the effect of combined sildenafil and NTG administration on defibrillation efficacy is not known.


OBJECTIVE
The present study investigated whether sildenafil administration at the therapeutic level increases the defibrillation threshold (DFT) when combined with NTG.


METHODS
Twenty-four pigs (20-25 kg) were randomized into four groups. After the control DFT was obtained, a stock solution of 50-mg (group 1, therapeutic concentration) and 100-mg (group 2, supratherapeutic concentration) of sildenafil, and 100-mL of saline (groups 3 and 4) were infused at 2 mL/min. Then, NTG was administered in groups 1-3 at 5 microg/min, with an increment of 5 microg/min every 5 min. The DFT was determined again after NTG was infused for 20 minutes.


RESULTS
In group 1, the DFT (402 +/- 33V, 11 +/- 2J) was not different from the control (404 +/- 28V, 11 +/- 2J). In group 2, the DFT (521 +/- 18V, 19 +/- 1J) was higher (p < 0.004) than that in the control group (444 +/- 31V, 14 +/- 2J). Saline did not alter the DFT either individually or in combination with NTG.


CONCLUSIONS
Supratherapeutic dose of sildenafil-NTG combination significantly increased the DFT (17% of peak voltage, 37% of total energy). This effect on DFT appears to be driven by sildenafil and not NTG.
Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Krekwit
K
Shinlapawittayatorn
Siriporn
S
Chattipakorn
Rattapong
R
Sungnoon
Nipon
N
Chattipakorn
D000818:Animals; D004554:Electric Countershock; D006352:Heart Ventricles / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D009206:Myocardium; D009569:Nitric Oxide / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D005996:Nitroglycerin