Effects of sildenafil citrate (Viagra) combined with nitrate on the heart.
BACKGROUND
Sildenafil citrate (Viagra) is indicated for the treatment of erectile dysfunction. Large and sudden decreases in systemic blood pressure were reported in a substantial number of patients taking sildenafil citrate combined with nitroglycerin. We studied the effect of sildenafil citrate on the relationship between changes in systemic blood pressure and coronary blood flow.


RESULTS
Healthy male beagles were used to assess systemic blood pressure, pulmonary arterial pressure, and flow in the left circumflex artery (in which a critical stenosis was established) and left anterior descending coronary artery. After measurement of the hemodynamic variables, 2 mg/kg sildenafil citrate was administered via a nasogastric tube. Hemodynamic changes were monitored for 1 hour. Subsequently, the acute effect of nitrate combined with sildenafil citrate was studied by the bolus injection of 0.2 mg isosorbide dinitrate before and after sildenafil citrate. Systemic blood and pulmonary arterial pressures and circumflex flow did not change during this study; however, left anterior descending coronary arterial flow increased from 16.0+/-5.8 to 24.6+/-8.7 mL/min 1 hour after administration of sildenafil citrate. The prolongation of systemic blood pressure decrease and the circumflex flow decrement induced by isosorbide dinitrate after sildenafil citrate were significantly larger and longer than those before sildenafil citrate.


CONCLUSIONS
Sildenafil citrate had the effect of vasodilation in a normal coronary artery; however, a combined effect with nitrate resulted in large and protracted decreases in systemic blood pressure and coronary blood flow in vessels with critical stenosis.
Ishikura
F
F
School of Allied Health Sciences, Osaka University, Faculty of Medicine, Osaka, Japan.
Beppu
S
S
Hamada
T
T
Khandheria
B K
BK
Seward
J B
JB
Nehra
A
A
D000284:Administration, Oral; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D001026:Coronary Artery Bypass; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy; D003331:Coronary Vessels / Q000187:drug effects / Q000601:surgery; D004285:Dogs; D004357:Drug Synergism; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D007548:Isosorbide Dinitrate / Q000008:administration & dosage*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage* / Q000097:blood; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011687:Purines; D000068677:Sildenafil Citrate; D013318:Stroke Volume / Q000187:drug effects; D013450:Sulfones; D014665:Vasodilator Agents / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D007548:Isosorbide Dinitrate