Abstract 19598: Evaluation of Left Ventricle Function and Oxidative Metabolism in Large Animal Model of Chronic Heart Failure

Abstract

Background and aims: Large animal model of chronic heart failure (HF) has been difficult to produce. Recently described pig model ofsurgical 2 step occlusion of the left anterior descending (LAD) coronary artery with distal ligation and proximal ameroid constrictor resulted in large anterior myocardial infarct (MI) with reasonable good survival (approx. 75% of animals alive at three months). We wanted to study by echocardiography and positron emission tomography (PET) the effects of proximal ligation of LAD in pig on LV remodelling and oxygen consumption during 3 months of follow-up. Methods: Male farm pigs ageing 3 weeks had either sham operation (control, n=4) or LAD occlusion (HF, n=8). Three months later, LV volumes (Modified Simpsons cylinder formula) were measured by transthoracic echocardiography (TTE). Myocardial kinetics k 1 and mono-exponential clearance rate of 11 C-acetate K mono were measured with PET to assess myocardial perfusion and oxidative metabolism, respectively. Results: None of the controls had MI, whereas seven of eight animals in the HF group had anterior MI scar as confirmed by TTC staining. PET perfusion showed average MI size of 26 ± 17 % of the LV in HF pigs. Echocardiography showed larger LV diastolic and systolic volumes in HF pigs than sham-operated pigs (diastolic volume 302±116 vs.109±28 ml, p=0.03; systolic 202±108 vs. 52±16 ml, p=0.05), whereas EF was lower (37±12 vs. 53±5 %, p=0.03). In the remote non-infarcted myocardium, perfusion and oxygen consumption was lower in HF than control pigs (k 1 0.78±0.13 vs. 1.26±0.41 ml/g/min p=0.01, K mono 0.114±0.024 vs. 0.146±0.008 min -1 , p=0.03). Conclusions: Surgical 2 step occlusion of the left anterior descending (LAD) coronary artery in pigs resulted in large area of myocardial infarction, reduced systolic function and LV remodelling. Consistent with HF, myocardial perfusion and oxygen consumption was reduced. Effects of therapeutic interventions on myocardial perfusion and oxygen consumption can be monitored in this model of chronic HF.