IMIPRAMINE INDUCED HEART-FAILURE IN THE DOG - A MODEL TO STUDY THE EFFECT OF CARDIAC ASSIST DEVICES

Objective: The value of intravenous imipramine in creating a reversible model of short term heart failure was evaluated in anaesthetised dogs. Methods: Acute effects of imipramine were studied in 11 dogs using invasive haemodynamic pressure measurements and two dimensional echo evaluation. Results: After a 30 min imipramine infusion (7.5 mg.kg-1.h-1), positive left ventricular dP/dt(max) decreased from 1368(SEM 108) to 909(119) mm Hg.s-1 (p<0.05), left ventricular end diastolic pressure increased from 8(1) to 12(2) mm Hg (p<0.05), while left ventricular pressure decreased from 106(4) to 87(6) mm Hg (p<0.05). Cessation of imipramine administration resulted within 60 min in partial restoration of cardiac function. This deterioration and subsequent recovery was also demonstrated with echocardiographic measurements, which showed a decrease in ejection fraction from 54(3)% to 28(2)% (p<0.05). During administration of imipramine neither significant electrophysiological changes nor supraventricular/ventricular arrhythmias were seen. Repeated infusions of imipramine in three anaesthetised dogs with a two week interval showed the reproducibility of the haemodynamic effects and the recovery of ventricular function. Since the model was developed to evaluate the use of cardiomyoplasty in heart failure, the effect of imipramine was also evaluated on latissimus dorsi muscle contraction. Administration of imipramine did not affect skeletal muscle force development at the dosage used to create heart failure. Conclusions: This model can be used to produce short term reversible heart failure in anaesthetised animals to test the efficacy of supportive interventions like dynamic cardiomyoplasty, intra-aortic balloon pumping, and mechanical cardiac assist devices.