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Titolo:
Female gender is a risk factor for drug-induced long QT and cardiac arrhythmias in an in vivo rabbit model
Autore:
Lu, HR; Remeysen, P; Somers, K; Saels, A; de Clerck, F;
Indirizzi:
Janssen Res Fdn, Dept Cardiovasc Safety Pharmacol, B-2340 Beerse, Belgium Janssen Res Fdn Beerse Belgium B-2340 Pharmacol, B-2340 Beerse, Belgium
Titolo Testata:
JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY
fascicolo: 5, volume: 12, anno: 2001,
pagine: 538 - 545
SICI:
1045-3873(200105)12:5<538:FGIARF>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
TORSADES-DE-POINTES; VENTRICULAR REPOLARIZATION; MYOCARDIAL-INFARCTION; EARLY AFTERDEPOLARIZATIONS; INCREASED DISPERSION; SUDDEN-DEATH; INTERVAL; HEART; PROLONGATION; DIFFERENCE;
Keywords:
long QT; QT/JT dispersion; gender; torsades de pointes; rabbit; I-K; blocker; proarrhythmias;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Lu, HR Janssen Res Fdn, Dept Cardiovasc Safety Pharmacol, Turnhoutseweg 30, B-2340 Beerse, Belgium Janssen Res Fdn Turnhoutseweg 30 Beerse Belgium B-2340 se, Belgium
Citazione:
H.R. Lu et al., "Female gender is a risk factor for drug-induced long QT and cardiac arrhythmias in an in vivo rabbit model", J CARD ELEC, 12(5), 2001, pp. 538-545

Abstract

Gender Differences in Drug-induced LQT and TdP. Introduction: Clinical observations and in vitro experimental data indicate that females have a longer QT interval than males, which is associated with a higher risk of drug-induced cardiac arrhythmias. Little is known about this gender difference in anesthetized animals, which may affect the outcome of in vivo drug tests. Methods and Results: We evaluated potential gender differences in ventricular repolarization (QT, QTc, JT, and JTc interval) and its dispersion, as well as in its response to dofetilide, an I-Kr blocker, in anesthetized rabbits challenged with the alpha (1)-adrenoceptor agonist methoxamine. A 12-lead ECG was recorded during the experiments. At baseline, there were no significant gender differences in ventricular repolarization values in male andfemale rabbits under anesthesia. Dofetilide (0.04 mg/kg/min TV for 60 min;n = 10 per gender) produced marked prolongation of the ventricular repolarization time and its dispersion, associated with a high incidence of polymorphic ventricular tachycardia (PVT; 100% in females vs 80% in males) and ventricular fibrillation (VF; 80% in females vs 50% in males; P > 0.05). QT and JT interval at 2 minutes as well as QT and JT dispersion at 10 and 30 minutes during dofetilide infusion were significantly higher in female than in male rabbits. After 30 minutes of dofetilide infusion, 10 of 10 female rabbits had severe cardiac arrhythmias (complete AV block, PVT, or VF), so ECG parameters were impossible to assess (vs 3/10 males with severe cardiac arrhythmias; P < 0.05). During dofetilide infusion, female rabbits developedcomplete AV block, PVT, or VF at doses about 50% lower than those given tomales. Conclusion: The present study indicates that female rabbits are more susceptible to drug-induced long QT and cardiac arrhythmias than are male rabbits; therefore, female rabbits are more appropriate for testing drug-induced cardiac arrhythmias.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/04/20 alle ore 11:49:45