title: Mitochondrial fusion proteins in revascularized hibernating hearts.
abstract: BACKGROUND
  Hibernating myocardium is characterized by viable yet dysfunctional myocardium secondary to chronic ischemia, with studies demonstrating incomplete early recovery after coronary artery bypass graft (CABG). We tested whether mitochondrial fusion proteins, an indicator of mitochondrial biogenesis, are increased in hibernating myocardium post-CABG.
  
  
  METHODS
  A constrictor was placed on the left anterior descending (LAD) artery of nine pigs. Four of these pigs additionally underwent CABG 12 wk later with a left internal mammary artery graft to the LAD distal to the constrictor. Five pigs had a constrictor placed but did not undergo CABG (Hib). Five pigs did not have a constrictor placed (control). Computerized tomography angiography was used to confirm stenosis at the site of constrictor placement and patency of left internal mammary artery grafts. Regional blood flows were determined at baseline and during 40 μg/kg/min dobutamine infusion. Mitochondrial proteins were quantified by Western blot.
  
  
  RESULTS
  Blood flow in the LAD region after CABG was lower than remote regions during dobutamine infusion (2.54 ± 0.24 versus 3.46 ± 0.33 mL/min/g; P < 0.05). Electron transport chain proteins were ∼70% lower in Hib compared with those in control and failed to normalize after CABG. Post-CABG, PGC1α nuclear-bound content was increased compared with Hib (9.02 ± 0.48 versus 5.54 ± 0.98 arbitrary units, respectively; P < 0.05), and expression of mitofusins-1 and 2 and optic atrophy-1 more than doubled.
  
  
  CONCLUSIONS
  PGC1α and mitochondrial fusion proteins are increased 4 wk post-CABG in hibernating hearts, indicating mitochondrial fusion has begun to occur and signaling early mitochondrial recovery. Future studies should address changes in maximal myocardial oxygen consumption relative to mitochondrial protein expression.
authors: Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
authors: Christopher T
authors: CT
authors: Holley
authors: Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
authors: Eric K
authors: EK
authors: Long
authors: Geriatric Research and Clinical Center (GRECC), Minneapolis Veterans Affairs Health Care System (VAHCS), Minneapolis, Minnesota; Department of Food Science and Nutrition, University of Minnesota, Minneapolis, Minnesota.
authors: Tammy A
authors: TA
authors: Butterick
authors: Geriatric Research and Clinical Center (GRECC), Minneapolis Veterans Affairs Health Care System (VAHCS), Minneapolis, Minnesota; Department of Food Science and Nutrition, University of Minnesota, Minneapolis, Minnesota.
authors: Cayla M
authors: CM
authors: Duffy
authors: College of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota.
authors: Megan E
authors: ME
authors: Lindsey
authors: Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
authors: Laura Hocum
authors: LH
authors: Stone
authors: Department of Cardiology, Minneapolis VAHCS, Minneapolis, Minnesota.
authors: Edward O
authors: EO
authors: McFalls
authors: Department of Surgery, University of Minnesota, Minneapolis, Minnesota; Department of Cardiothoracic Surgery, Minneapolis VAHCS, Minneapolis, Minnesota. Electronic address: kelly071@umn.edu.
authors: Rosemary F
authors: RF
authors: Kelly
mesh_terms: D000818:Animals; D001026:Coronary Artery Bypass; D003326:Coronary Circulation; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D005260:Female; D024101:Mitochondrial Proteins / Q000378:metabolism*; D063269:Mitochondrial Turnover; D009204:Myocardial Revascularization; D017682:Myocardial Stunning / Q000378:metabolism / Q000601:surgery*; D013552:Swine
chemical_list: D045222:Electron Transport Chain Complex Proteins; D024101:Mitochondrial Proteins
keywords: Animal model of cardiovascular disease; Coronary artery bypass graft surgery; Hibernating myocardium; Ischemic heart disease; Mitochondrial disease cardiomyopathy