title: Left ventricular mechanical unloading restores Beta-2-adrenergic receptor mRNA expression and decreases susceptibility to ischemia and reperfusion in the failing heart.
abstract: OBJECTIVE
  Left ventricular (LV) mechanical unloading is known to reduce the hemodynamic demands of failing LV, resulting in improved myocyte contractility. This study was designed to examine effects of LV unloading on beta-adrenergic receptor (BAR) expression and ischemic susceptibility to ischemia reperfusion.
  
  
  METHODS
  Five groups were studied: group 1 [unloading myocardial infarction (MI), n = 6], MI hearts 2 weeks after coronary ligation subjected to LV unloading by heterotopic heart transplantation for 2 weeks; group 2 (2-week MI, n = 6), MI hearts left for 2 weeks without unloading; group 3 (4-week MI, n = 6), MI hearts left for 4 weeks without unloading; group 4 (control, n = 6), normal (non-MI) hearts as a control with no interventions, and group 5 (unloading control, n = 5), normal (non-MI) hearts subjected to LV unloading for 2 weeks. Then, all hearts were isolated and subjected to 20 min of global ischemia and 60 min of reperfusion on Langendorff apparatus. LV pressures and coronary flow were measured throughout the experiment. Either total BAR density or beta(2)-adrenergic receptor (B2AR) mRNA expression in the noninfarcted myocardium was determined by radioligand binding assays or real-time quantitative RT-PCR, respectively.
  
  
  RESULTS
  LV unloading improved postischemic functional recovery (unloading MI vs. 2-week MI vs. 4-week MI: 74 +/- 6 vs. 54 +/- 5 vs. 51 +/- 4%; p < 0.05 vs. unloading MI). LV unloading restored B2AR mRNA expression (unloading MI vs. 2-week MI vs. 4-week MI: 4.78 +/- 0.21 vs. 2.80 +/- 0.19 vs. 2.24 +/- 0.17 x 10(7) copy/microg total RNA; p < 0.05 vs. unloading MI).
  
  
  CONCLUSIONS
  LV mechanical unloading restored B2AR mRNA expression and improved postischemic functional recovery.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, Takatsuki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakahara
authors.forename: H
authors.initials: H
authors.lastname: Horimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Nakai
authors.forename: S
authors.initials: S
authors.lastname: Mieno
authors.forename: Y
authors.initials: Y
authors.lastname: Nomura
authors.forename: S
authors.initials: S
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D015870:Gene Expression; D006333:Heart Failure / Q000503:physiopathology*; D016027:Heart Transplantation; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010477:Perfusion; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D020127:Recovery of Function; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*
chemical_list: D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2