ELECTROPHYSIOLOGICAL CHANGES IN ANIMAL-MODEL OF CHRONIC CARDIAC-FAILURE

Study objective - The aim of the study was to examine right ventricular electrophysiological changes in an animal model of chronic cardiac failure.Design - Cardiac failure was induced in rabbits by intravenous doxorubicin 1 mg·kg-1 twice weekly for 8 weeks. Controls were injected with saline. Electrophysiological recordings were made in conscious animals using bipolar pacing electrodes implanted in the right ventricular apex.Subjects - Adult male New Zealand white rabbits, weight 2.5-3.5 kg, were used (n=27 doxorubicin treated, 20 control).Measurements and main results - Recordings were made of effective refractory period and of the stimulus-T interval (Stim-T) of the paced evoked response, an index of ventricular repolarisation time. Progressive shortening of Stim-T and effective refractory period occurred in doxorubicin treated animals, with a reduction of 12% in repolarisation and 14% in refractoriness by week 10. No significant changes in Stim-T or effective refractory period occurred in controls. Right ventricular papillary muscles from doxorubicin treated animals in vitro also showed shortening of intracellular action potential duration and effective refractory period compared with controls. Changes in the doxorubicin treated animals were not attributable to a direct acute electrophysiological effect of doxorubicin or to differences in plasma electrolytes, noradrenaline or renin.Conclusions - Shortening of ventricular repolarisation and refractory period in heart failure may represent an intrinsic mechanism predisposing to arrhythmia and sudden death.