Chronic Electrophysiological Changes in Adriamycin Cardiomyopathy in the Rabbit

Doherty, John D (1992) Chronic Electrophysiological Changes in Adriamycin Cardiomyopathy in the Rabbit. MD thesis, University of Glasgow.

Abstract

Sudden cardiac death accounts for 35-45% of all deaths in heart failure, presumably from malignant ventricular arrhythmias. The aetiology of sudden arrhythmic death has not been fully elucidated, although a number of mechanisms exist which could potentially be arrhythmogenic. These include activation of the renin-angiotensin system, an increase in sympathetic nervous activity, electrolyte depletion and the use of inotropes and diuretics. It is likely however, that these mechanisms are secondary to the underlying electrophysiological changes in the myocardium resulting from the processes of myocyte damage and necrosis, compensatory hypertrophy and fibrosis which occur in the failing heart. In order to understand the basic mechanisms responsible for sudden death in heart failure, there is a need for animal models in which the electrophysiological changes produced by myocardial damage and the interrelationship between the myocardial electrophysiological substrate, neurohormonal activity and inducibility of arrhythmias can be studied in detail. In this study cardiac failure was induced in rabbits by injection of the cardiotoxin adriamycin 1mg/Kg twice weekly for 8 weeks. Electrophysiological recordings were made in conscious animals using bipolar pacing electrodes, implanted in the right ventricular apex. Recordings were made of the effective refractory period and the Stimulus-T interval of the paced evoked response. Neurohormonal assays and measurement of plasma electrolytes were undertaken during the study, and pathological analysis when the animals died. Progressive shortening in the stimulus-T interval and effective refractory period occurred in the adriamycin treated animals. No significant changes were seen in controls. Right ventricular papillary muscles from uninstrumented animals were used for in vitro electrophysiological studies. Action potential duration and effective refractory period were significantly shorter in the adriamycin group compared to controls. The changes in these electrophysiological parameters were independent of changes in plasma electrolytes and neurohormones. Captopril did not reverse the electrophysiological changes, but did cause a reduction in heart and liver weight, and ventricular ectopic activity. A cohort of animals treated with adriamycin and frusemide did not have a progressive shortening in effective refractory period and stimulus-T interval, and this questions the reproducibility of the electrophysiological changes in the study.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Additional Information: Adviser: S M Cobbe
• Keywords: Medicine
• Date of Award: 1992
• Depositing User: Enlighten Team
• Unique ID: glathesis:1992-76323
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Nov 2019 15:46
• Last Modified: 19 Nov 2019 15:46
• URI: https://theses.gla.ac.uk/id/eprint/76323