title: Severe mechanical dyssynchrony causes regional hibernation-like changes in pigs with nonischemic heart failure.
abstract: BACKGROUND
  Sustained left ventricular (LV) dyssynchrony can lead to heart failure (HF) in the absence of coronary artery stenosis. We tested whether myocardial hibernation underlies the LV functional impairment caused by high-frequency pacing, an established model of nonischemic dilated cardiomyopathy.
  
  
  RESULTS
  Regional LV contractile and perfusion reserve were assessed by magnetic resonance imaging, respectively, as end-systolic wall thickening (LVESWT) and myocardial perfusion reserve index (MPRI) at rest and during low-dose dobutamine stress (LDDS, 10 microg.kg.min intravenously for 10minutes) in failing minipigs (n=8). LV tissue was analyzed for glycogen deposits and other molecular hallmarks of hibernation. LDDS caused a marked increase in LVESWT (27+/-2.98 vs. 7.15+/-3 %, P < .05) and MPRI (2.1+/-0.5 vs. 1.3+/-0.3 P < .05) in the region that was activated first (pacing site) compared with the opposite region. Myocardial glycogen content was markedly increased in the pacing site (P < .05 vs. opposite region). In addition, gene expression of glycogen phosphorylase was reduced in pacing site compared with opposite regions (0.71+/-0.1 vs. 1.03+/-0.3, P < .05), whereas that of hexokinase type II was globally reduced by 83%.
  
  
  CONCLUSIONS
  The combination of high heart rate and sustained dyssynchronous LV contraction causes asymmetrical myocardial hibernation, in absence of coronary artery stenosis.
authors: Sector of Medicine, Scuola Superiore Sant'Anna, Pisa, Italy; National Institute of Biostructures and Biosystems, Bologna, Italy.
authors: Vincenzo
authors: V
authors: Lionetti
authors: Giovanni D
authors: GD
authors: Aquaro
authors: Anca
authors: A
authors: Simioniuc
authors: Claudio
authors: C
authors: Di Cristofano
authors: Francesca
authors: F
authors: Forini
authors: Federica
authors: F
authors: Cecchetti
authors: Manuela
authors: M
authors: Campan
authors: Daniele
authors: D
authors: De Marchi
authors: Fabio
authors: F
authors: Bernini
authors: Maria
authors: M
authors: Grana
authors: Monica
authors: M
authors: Nannipieri
authors: Massimiliano
authors: M
authors: Mancini
authors: Massimo
authors: M
authors: Lombardi
authors: Fabio A
authors: FA
authors: Recchia
authors: Alessandro
authors: A
authors: Pingitore
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D004195:Disease Models, Animal; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology*; D006605:Hibernation / Q000502:physiology*; D008297:Male; D012720:Severity of Illness Index; D013552:Swine; D013556:Swine, Miniature; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000503:physiopathology*