Flow-function relations in a canine model of progressive ischaemic cardiomyopathy

The controversy regarding the mechanism(s) of regional and global left ventricular (LV) dysfunction in chronic coronary artery disease (CAD) is in part related to the lack of an animal model of this condition. Ameroid constrictors were placed on proximal portions of coronary arteries in dogs, who were then euthanised weeks later (mean 6 weeks) after the development of severe global LV dysfunction. Coronary stenosis was confirmed with angiography. Radiolabelled-microsphere derived myocardial blood flow (MBF) and 2-dimensional echocardiographic regional and global LV systolic function were quantified over the observation period. Wall thickening was quantified throughout systole, providing information on final percent thickening and the rate of thickening. No evidence of infarction was found in the majority of the 12 dogs on histopathology. Minor patchy necrosis was noted in 8 of 24 beds examined. The LV size increased and end-systolic size almost doubled (p<0.01). Percent change in area from end-diastole to end-systole decreased by >50% (p<0.01). Regional dysfunction was noted in 23 of 24 myocardial beds analysed. In 12 beds, severe dysfunction was noted without a decrease in resting MBF. In 11 beds, decrease in function was associated with a decrease in resting MBF (p<0.01), and in these beds close coupling between percent wall thickening and MBF was noted. In all segments that exhibited an ultimate decrease in MBF, decrease in function preceded the decrease in MBF. In all dysfunctional beds irrespective of MBF at rest, the rate of systolic thickening was shown to fall (tardokinesis) at the end of the study compared to baseline (p<0.01). We have developed a canine model of chronic ischaemic LV dysfunction that closely mimics the human condition and may be used to further our understanding of this condition.