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Titolo:
Cardiac electrophysiologic and hemodynamic effects of sildenafil, a PDE5 inhibitor, in anesthetized dogs
Autore:
Sugiyama, A; Satoh, Y; Shiina, H; Takahara, A; Yoneyama, M; Hashimoto, K;
Indirizzi:
Yamanashi Med Univ, Dept Pharmacol, Tamaho, Yamanashi 4093898, Japan Yamanashi Med Univ Tamaho Yamanashi Japan 4093898 amanashi 4093898, Japan
Titolo Testata:
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
fascicolo: 6, volume: 38, anno: 2001,
pagine: 940 - 946
SICI:
0160-2446(200112)38:6<940:CEAHEO>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VIVO; DE-POINTES; REPOLARIZATION; DRUG; TORSADES; CITRATE; VIAGRA; AGENTS; TISSUE;
Keywords:
monophasic action potential; effective refractory period; I-Kr; sildenafil; repolarization;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Sugiyama, A Yamanashi Med Univ, Dept Pharmacol, Tamaho, Yamanashi 4093898,Japan Yamanashi Med Univ Tamaho Yamanashi Japan 4093898 3898, Japan
Citazione:
A. Sugiyama et al., "Cardiac electrophysiologic and hemodynamic effects of sildenafil, a PDE5 inhibitor, in anesthetized dogs", J CARDIO PH, 38(6), 2001, pp. 940-946

Abstract

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 themonophasic action potential duration or effective refractory period of theright 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 activationassociated 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 02:35:35