Background We tested the hypothesis that hibernating myocardium repres
ents an incomplete adaptation to a reduced myocardial oxygen supply, M
ethods and Results In 38 patients, areas of hibernating myocardium wer
e identified by angiography, multigated radionuclide ventriculography,
thallium scintigraphy with reinjection, and low-dose dobutamine echoc
ardiography. Biopsies removed at cardiac surgery showed structural deg
eneration characterized by a reduced protein and mRNA expression and d
isorganization of the contractile and cytoskeletal proteins myosin, ac
tin, desmin, titin, alpha-actinin. and vinculin by electron microscopy
, immunohistochemistry, and in situ hybridization. Additionally, an in
creased amount of extracellular matrix proteins resulting in a signifi
cant degree of reparative fibrosis was present. Dedifferentiation, ie,
expression of fetal proteins, was absent. Apoptosis indicating suicid
al cell death was found by the terminal deoxynucleotidyl transferase e
nd-labeling method and electron microscopy. Radionuclide ventriculogra
phy showed improvement of regional function at 3 months postoperativel
y compared with preoperative values (mean values, 23.5% and 45%, respe
ctively), and the echocardiographic wall-motion score index decreased
from 3.4 to 1.8. The degree of severity of the morphological changes (
three stages) correlated well with the extent of postoperative functio
nal recovery: more advanced clinical improvement was observed in patie
nts with slight and moderate morphological degeneration (stages 1 and
2), but recovery was only partial in severe degeneration (stage 3). Co
nclusions Cellular degeneration rather than adaptation is present in h
ibernating myocardium. The consequence is progressive diminution of th
e chance for complete structural and functional recovery after restora
tion of blood flow. The practical consequence from this study should b
e early revascularization in patients showing areas of hibernating myo
cardium.