Severe mechanical dyssynchrony causes regional hibernation-like changes in pigs with nonischemic heart failure.
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.
Lionetti
Vincenzo
V
Sector of Medicine, Scuola Superiore Sant'Anna, Pisa, Italy; National Institute of Biostructures and Biosystems, Bologna, Italy.
Aquaro
Giovanni D
GD
Simioniuc
Anca
A
Di Cristofano
Claudio
C
Forini
Francesca
F
Cecchetti
Federica
F
Campan
Manuela
M
De Marchi
Daniele
D
Bernini
Fabio
F
Grana
Maria
M
Nannipieri
Monica
M
Mancini
Massimiliano
M
Lombardi
Massimo
M
Recchia
Fabio A
FA
Pingitore
Alessandro
A
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*