Importance of extracardiac alpha1-adrenoceptor stimulation in assisting dofetilide to induce torsade de pointes in rabbit hearts

European Journal of Pharmacology
A FarkasAndrás Farkas

Abstract

In anaesthetized rabbits, alpha(1)-adrenoceptor stimulation increases the propensity of repolarization-prolonging drugs to induce torsade de pointes ventricular tachycardia. However, it is not known whether the stimulation of intracardiac alpha(1)-adrenoceptors, or the increased ventricular stretch caused by extracardiac alpha(1)-adrenoceptor-mediated peripheral vasoconstriction and increased resistance, are the sensitizing factors. Accordingly, this study investigated whether a sustained load-induced left ventricular stretch or stimulation of the intracardiac alpha(1)-adrenoceptors with 100 nM methoxamine, or the co-application of these two, can assist dofetilide (100 nM) to elicit torsade de pointes in isolated Langendorff-perfused, rabbit hearts. In the stretched hearts, a constant high level of stretch was produced by a water-filled left ventricular balloon inflated to a volume of 1.4 ml, whereby the systolic and end-diastolic pressures virtually did not exceed the physiological range (<or=157+/-11 mm Hg and <or=9+/-2 mm Hg, respectively; mean+/-S.E.M.). Perfusion with dofetilide prolonged the QT interval significantly and indifferently in all hearts. Neither this stretch nor methoxamine nor the in combination affected the ...Continue Reading

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Aug 7, 2002·European Journal of Pharmacology·András Farkas, Susan J Coker
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Jul 23, 2003·European Journal of Pharmacology·András Farkas, Susan J Coker
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Citations

Jul 1, 2009·Future Medicinal Chemistry·Jacques HamonLaszlo Urban
Jun 14, 2013·Journal of Pharmacology & Pharmacotherapeutics·Shailaja B KhobragadeVyas M Shingatgeri
Jul 22, 2015·Nature Reviews. Cardiology·Gerrit Frommeyer, Lars Eckardt
Jun 19, 2008·Pharmacology & Therapeutics·Leif Carlsson
Nov 29, 2008·Progress in Biophysics and Molecular Biology·Stanley NattelLeif Carlsson
Jun 3, 2014·Journal of Cardiovascular Pharmacology·Szabolcs OroszAndrás Farkas
Nov 22, 2015·British Journal of Pharmacology·P ChamperouxJ Thireau
Jun 26, 2020·Frontiers in Pharmacology·István BaczkóKatja E Odening

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