Cardiac Electrophysiologic and Hemodynamic Effects of Sildenafil, a PDE5 Inhibitor, in Anesthetized Dogs
| Autor: | Yoshioki Satoh, Akira Takahara, Keitaro Hashimoto, Hiroyuki Shiina, Atsushi Sugiyama, Masahiko Yoneyama |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Inotrope Chronotropic Bundle of His medicine.medical_specialty Refractory Period Electrophysiological Phosphodiesterase Inhibitors Sildenafil Action Potentials Blood Pressure Vasodilation Piperazines Sildenafil Citrate Electrocardiography chemistry.chemical_compound Dogs 3' 5'-Cyclic-GMP Phosphodiesterases Heart Rate Internal medicine Potassium Channel Blockers Ventricular Pressure Animals Repolarization Medicine Anesthesia Sinus rhythm Sulfones Cyclic Nucleotide Phosphodiesterases Type 5 Pharmacology business.industry Cardiac Pacing Artificial Electric Conductivity Hemodynamics Effective refractory period respiratory tract diseases chemistry Purines cGMP-specific phosphodiesterase type 5 Ventricular Function Right cardiovascular system Cardiology Female Vascular Resistance Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of Cardiovascular Pharmacology. 38:940-946 |
| ISSN: | 0160-2446 |
| Popis: | Summary: A recent in vitro study demonstrated that supratherapeutic concentrations of sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, blocked I Kr and prolonged cardiac repolarization. This study assessed the in vivo cardiohemodynamic and electrophysiologic effects of sildenafil using a halothane-anesthetized, closed-chest canine model (n = 5) to bridge the gap between basic observation and clinical experience. Intravenous administration of sildenafil citrate in doses of 0.03, 0.3, and 3.0 mg/kg for 10 min, which provided sub-to supratherapeutic plasma drug concentrations, did not affect the monophasic action potential duration or effective refractory period of the right ventricle during the sinus rhythm as well as the ventricular pacing at the cycle length of 400 and 300 ms. However, sildenafil decreased the total peripheral resistance, simultaneously inducing positive chronotropic and inotropic effects at the top dose, which gave plasma concentrations at least 10 times higher than the therapeutic range. This cardiohemodynamic profile of sildenafil can be largely explained by reflex sympathetic activation associated with its vasodilator effect. Meanwhile, the lack of prolongation of the ventricular repolarization phase at the therapeutically relevant to moderately supratherapeutic sildenafil concentrations supports the earlier clinical studies that indicate that sildenafil has no effect on electrocardiogram. |
| Databáze: | OpenAIRE |
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