Electrophysiological changes in animal model of chronic cardiac failure.
OBJECTIVE
The aim of the study was to examine right ventricular electrophysiological changes in an animal model of chronic cardiac failure.


METHODS
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.


METHODS
Adult male New Zealand white rabbits, weight 2.5-3.5 kg, were used (n = 27 doxorubicin treated, 20 control).


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.
Doherty
J D
JD
Department of Medical Cardiology, Royal Infirmary, Glasgow, Scotland.
Cobbe
S M
SM
D000200:Action Potentials; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D004195:Disease Models, Animal; D004317:Doxorubicin; D004562:Electrocardiography; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009638:Norepinephrine / Q000097:blood; D011817:Rabbits; D012083:Renin / Q000097:blood; D013997:Time Factors
D004317:Doxorubicin; D009320:Atrial Natriuretic Factor; D012083:Renin; D009638:Norepinephrine