13th International Congress
THE "NEW FRONTIERS"
OF ARRHYTHMIAS 1998

January 24-31, 1998
Marilleva, Trento, Italy

RT-83

Arrhythmogenic alterations in failing human ventricular myocytes

Elisabetta Cerbai*, Roberto Pino*, Laura Sartiani*, Guido Sani°, Gianfranco Lisi#, Federico Bizzarri#, Giuseppe Vaccari#, Alessandro Mugelli*.
*Department of Pharmacology, University of Florence, °Cardiosurgery, University of Cagliari, #Thoracic Cardiosurgery, University of Siena, Italy

Abstract

Background. The electrophysiologic behavior of the heart is altered in disease. Recent studies have documented that the electrophysiological properties of cardiac cells are markedly modified in terminal heart failure.

Methods. Left ventricular myocytes were prepared using enzymatic procedures from one donor heart and from hearts explanted for terminal heart failure. Action potentials and ionic currents were recorded using the patch clamp technique.

Results. The action potential recorded from "failing" ventricular myocytes was markedly prolonged compared to that recorded from normal myocytes. A specific reduction in the transient outward current I_to has been reported to be the ionic mechanism responsible for this phenomenon. Myocytes isolated from the failing heart express a current activated by hyperpolarization and having the properties of the pacemaker current I_f. Current amplitude is much larger in "failing" myocytes than in normal ones. Due to its small amplitude at potentials near the maximum diastolic potential (approximately -80 mV in our undiseased ventricular myocytes), it is unlikely that I_f contributes to membrane depolarisation under normal conditions. However, its contribution to diastolic depolarisation is likely to be relevant in the failing heart since its amplitude is markedly larger in "failing" myocytes.

Conclusions. The cellular electrophysiological alterations found in left ventricular myocytes isolated from the failing human heart are likely to be arrhythmogenic. A non homogeneous decrease in I_to might cause in the intact heart a dispersion of repolarization which is potentially arrhythmogenic. The expression of the pacemaker current may "destabilise" the membrane potential and by interacting with delayed afterdepolarizations, may cause extrasystoles which can serve as a trigger for ventricular arrhythmias in hearts in which the substrate for arrhythmias is definitely present.

Key Words

Molecular biology - mechanisms of arrhythmogenesis 
heart failure, failing ventricular myocytes, cellular ionic mechanisms, arrhythmogenic mechanisms, experimental arrhytmology, OA