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Am J Physiol Heart Circ Physiol (January 17, 2002). doi:10.1152/ajpheart.00138.2001
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Articles in PresS, published online ahead of print January 17, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00138.2001
Submitted on March 1, 2001
Accepted on December 26, 2001

Ischemic Cardiomyopathy in Pigs with 2-Vessel Occlusionand Viable, Chronically Dysfunctional Myocardium

James A Fallavollita1 and John M Canty, Jr.1*

1 Department of Medicine Division of Cardiology, University at Buffalo, Buffalo, NY; Western NY Healthcare System, Department of Veterans Affairs, Buffalo, NY

* To whom correspondence should be addressed. E-mail: canty{at}buffalo.edu.

A chronic LAD stenosis leads to the development of hibernating myocardium with severe regional hypokinesis but normal global ventricular function after 3-months. We hypothesized that 2-vessel occlusion would accelerate the progression to hibernating myocardium and lead to global LV dysfunction and heart failure. Pigs were instrumented with a fixed 1.5 mm constrictor on the proximal LAD and circumflex arteries. After 2-months there were no overt signs of right-heart failure and TTC infarction was trivial (1.4±0.1% of the LV). In comparison to shams, regional function ({Delta}WT; 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/g, 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%, p<0.05 vs. shams). Early LV remodeling was present with increases in cavity size and mass. Reductions in SR calcium ATPase and phospholamban were confined to the dysfunctional LAD region with no change in calsequestrin. Thus, combined stenoses of the LAD and circumflex arteries accelerates the development of hibernating myocardium and results in compensated heart failure.




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