title: Expression of uncoupling protein-2 remains increased within hibernating myocardium despite successful coronary artery bypass grafting at 4 wk post-revascularization.
abstract: BACKGROUND
  We have previously shown that mitochondrial uncoupling protein-2 (UCP-2) is increased in a swine model of hibernating myocardium (HM). Although UCP-2 reduces oxidant stress, it can promote inefficiency of the electron transport chain. In this study, we tested whether UCP-2 remains increased in revascularized HM (RHM) after coronary artery bypass grafting (CABG).
  
  
  METHODS
  Seven swine underwent thoracotomy with placement of a constrictor on the left anterior descending artery (LAD). Twelve weeks later, a left internal mammary artery graft was placed on the distal LAD. Four weeks post-CABG, computed tomography angiography documented patent grafts and function. At the terminal study, blood flow to the LAD and remote territories were assessed during high dose dobutamine and mitochondria isolated from both regions for analysis. Comparisons were made to a group of swine with HM who underwent constrictor placement without bypass grafting (n = 4).
  
  
  RESULTS
  During dobutamine infusion, RHM demonstrated lower blood flows (2.44 ± 0.23 versus 3.43 ± 0.30 mL/min/g; P < 0.05) and reduced wall thickening (33 ± 9% versus 52 ± 13%; P < 0.05) compared with remote regions. RHM had lower respiratory control indices (3.7 ± 0.3 versus 4.3 ± 0.4; P < 0.05) with persistently increased UCP-2 content.
  
  
  CONCLUSIONS
  Despite patent grafts, RHM demonstrates a submaximal response to dobutamine infusion and increased mitochondrial UCP-2 expression. These data support the notion that recovery of the mitochondria in RHM is delayed early post-CABG and may contribute to impaired oxygen consumption and contractile reserve during catecholamine challenges.
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Holley
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, Minneapolis, MN; Geriatric Research and Clinical Center (GRECC), Minneapolis Veterans Affairs Health Care System (VAHCS), Minneapolis, MN.
authors.forename: Cayla M
authors.initials: CM
authors.lastname: Duffy
authors.affiliation: Department of Food Science and Nutrition, University of Minnesota, Minneapolis, MN; Geriatric Research and Clinical Center (GRECC), Minneapolis Veterans Affairs Health Care System (VAHCS), Minneapolis, MN.
authors.forename: Tammy A
authors.initials: TA
authors.lastname: Butterick
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Long
authors.affiliation: College of Medicine, University of Minnesota, Minneapolis, MN.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Lindsey
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN.
authors.forename: Jesús A
authors.initials: JA
authors.lastname: Cabrera
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN; Department of Cardiothoracic Surgery, Minneapolis VAHCS, Minneapolis, MN.
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Ward
authors.affiliation: Department of Cardiology, Minneapolis VAHCS, Minneapolis, MN.
authors.forename: Edward O
authors.initials: EO
authors.lastname: McFalls
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN; Department of Surgery, University of Minnesota, Minneapolis, MN. Electronic address: kelly071@umn.edu.
authors.forename: Rosemary F
authors.initials: RF
authors.lastname: Kelly
mesh_terms: D000818:Animals; D057791:Cardiac Imaging Techniques; D002316:Cardiotonic Agents / Q000494:pharmacology; D019069:Cell Respiration; D002908:Chronic Disease; D001026:Coronary Artery Bypass; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology; D015150:Echocardiography, Doppler; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D007473:Ion Channels / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D017682:Myocardial Stunning / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014057:Tomography, X-Ray Computed; D000071246:Uncoupling Protein 2
chemical_list: D002316:Cardiotonic Agents; D007473:Ion Channels; D024101:Mitochondrial Proteins; D000071246:Uncoupling Protein 2; D004280:Dobutamine
keywords: Coronary Artery Bypass Grafting; Hibernating Myocardium; Mitochondria; Revascularization; Uncoupling Protein-2