Abstract 16148: Uncoupling Protein-2 Remains Increased in Hibernating Myocardial Tissue Despite Successful Coronary Artery Revscularization
Clinical studies indicate that functional recovery of hibernating myocardium is incomplete following coronary artery bypass surgery (CABG). Consistent with these observations, we have shown in a swine model of chronic hibernating myocardium that recruitment of maximal blood flow and function remains depressed, despite successful CABG. In the present study, we hypothesized that expression of uncoupling protein (UCP)-2 is increased in revascularized hibernating myocardial regions that fail to respond normally to a catecholamine stress.
Methods. Nine pigs underwent thoracotomy with placement of a constrictor around the LAD artery. After 12 weeks, they underwent sternotomy and off-pump revascularization with a left internal mammary artery graft to the LAD just beyond the chronic stenosis. Graft patency was confirmed in all pigs by CTA at 4 weeks. Six pigs underwent a SHAM operation for comparison. Prior to sacrifice, regional blood flows (µspheres) were determined at baseline and during a high dose dobutamine infusion (40 µg/kg/min). Post-sacrifice, mitochondria were isolated and UCP-2 content was determined by western gels.
Results. Baseline blood flow in the Revascularized Hibernating (R-HIB) and SHAM LAD regions were 0.60±0.05 and 0.71±0.11 ml/ming respectively (NS). At high work state however, regional blood flow in the R-HIB-LAD region was lower when normalized to the remote region and mitochondrial expression of UCP-2 content was higher compared with SHAM-LAD hearts (Figure 1).
Conclusion. Despite successful revascularization of hibernating heart tissue, maximal blood flow in response to a catecholamine challenge remains depressed and expression of UCP-2 is abnormally increased. These data support the concept that the mitochondrial proteome within the distribution of chronically ischemic hibernating heart tissue remains abnormal despite revascularization and may attenuate maximal oxygen consumption and expenditure during high work states.
- Cardiac surgery
- Mitochondrial energetics, heart failure, arrhythmias
- Myocardial revascularization
- Ischemic heart disease
- © 2012 by American Heart Association, Inc.