Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium

A chronic left anterior descending coronary artery (LAD) stenosis leads to the development of hibernating myocardium with severe regional hypokinesis but normal global ventricular function after 3 mo. We hypothesized that two-vessel occlusion would accelerate the progression to hibernating myocardium and lead to global left ventricular (LV) dysfunction and heart failure. Pigs were instrumented with a fixed 1.5-mm constrictor on the proximal LAD and circumflex arteries. After 2 mo, there were no overt signs of right-heart failure and triphenyl tetrazolium chloride infarction was trivial (1.4 ± 0.1% of the LV). Compared with shams, regional function [myocardial systolic excursion (ΔWT); 2.1 ± 0.3 vs. 4.6 ± 0.4 mm, P < 0.05] and resting perfusion (0.90 ± 0.13 vs. 1.32 ± 0.09 ml·min^-1·g-^-1, P < 0.05) were reduced, consistent with hibernating myocardium. Pulmonary systolic (45.9 ± 3.3 vs. 36.5 ± 2.2 mmHg, P < 0.05) and wedge pressures (19.1 ± 1.6 vs. 11.2 ± 0.9 mmHg, P < 0.05) were increased with global ventricular dysfunction (ejection fraction 43 ± 2 vs. 50 ± 2%, P < 0.05). Early LV remodeling was present with increased cavity size and mass. Reductions in sarcoplasmic reticulum Ca²⁺-ATPase and phospholamban were confined to the dysfunctional LAD region with no change in calsequestrin. Thus combined stenoses of the LAD and circumflex arteries accelerate the development of hibernating myocardium and result in compensated heart failure.