Drug-induced torsades de pointes — A form of mechano-electric feedback?

Abstract

See article by Gallacher et al. [1] (pages 247–256) in this issue. In this issue of Cardiovascular Research , Gallacher et al. report findings on a novel canine model of drug-induced long-QT syndrome [1]. In this model, torsades de pointes (TdP) arrhythmia was induced in anaesthetised dogs by bolus injections of the β-adrenoreceptor agonist isoproterenol during selective inhibition of the slow component of the delayed-rectifier potassium current I Ks by HMR1556. Isoproterenol induced TdP in 94% of dogs tested. Authors examined the interaction of putative mechanisms of induction of TdP. Blockade of I Ks mimics the functional effects of the genetic alterations found in long-QT syndrome type I. The β-adrenergic challenge caused action potential prolongation and increased spatial [2–4] and temporal [2] dispersion of repolarisation. Systolic aftercontractions, measured as small increases in left ventricular systolic pressure, preceded the onset of TdP (see Fig. 4 in the manuscript). TdP and aftercontractions were able to be suppressed by either β-adrenoreceptor blockade by esmolol or calcium channel blockade by verapamil, as expected [5,6]. The simultaneous real-time recording of surface ECG, several monophasic action potentials (MAP), and pressure from both ventricles in the dog gives us valuable insight into the … *Tel.: +49 251 83 46034; fax: +49 251 83 47864. fabritzl{at}uni-muenster.de