Structural correlates of regional myocardial dysfunction in patients with critical coronary artery stenosis: Chronic hibernation?

Structural remodelling of cardiomyocytes in the border zone of infarcted rabbit heart

“…Furthermore, within the border zone of infarcted myocardium viable vacuolated cells were observed which were surrounded by fibrotic tissue. Co-culturing of adult rabbit CM's with cardiac fibroblasts resulted in typical structural characteristics of CM dedifferentiation, resembling human myocardial hibernation [3,12,13,16]. Such hibernating cardiomyocytes have previously been reported at the borders of micro-infarctions induced in sheep after injection of macro-beads into the LAD or CX coronary artery [5] and in regions bordering fibrous scars of dogs with heart failure [4].…”

“…They lose cell-cell connections because of the death of neighbouring cardiomyocytes and subsequent anchoring to scar tissue [2]. Furthermore, it has been shown that the border zone of infarcted myocardium in larger animals such as dog and sheep may comprise a considerable number of dedifferentiated CM's, which are phenotypically similar to those seen in chronic hibernation [3][4][5]. Partial dedifferentiated cardiomyocytes have recently been described as well in the border zone of rat myocardium after myocardial infarction [6].…”

“…5 consecutive slices (I to V) were made of the rabbit heart immediately after perfusion fixation. Several samples were taken from the border zone of infarcted myocardium (1), from the adjacent non-infarcted region (2) and from the remote zone of the left ventricle (3) Localization of hibernating cardiomyocytes…”

“…Hibernation of the myocardium was originally described as a protective mechanism of the heart in which it down regulates its contracting function to cope with oxygen shortage, caused by a chronic or repetitive underperfusion accompanied by a limited flow reserve [7]. The most obvious subcellular changes in these dedifferentiated CM's were described later on and comprised sarcomere depletion, glycogen accumulation, nuclear heterochromatin redistribution, mitochondrial shape changes and sarcoplasmic reticulum breakdown, giving the CM's a fetal/ neonatal-like phenotype [3]. After revascularisation, the hibernating segments often show a delayed recovery of function which can take a few months to more than one year in a fraction of patients with chronic hibernating myocardium [8].…”

Viability testing to guide myocardial revascularisation in patients with heart failure

“…Histologically, hibernating myocardium is characterised by cardiomyocyte dedifferentiation, with loss of sarcomeres, sarcoplasmic reticulum and T-tubules, alongside abundant glycogen and nuclear changes with heterochromatin redistribution. [17] In animal models of regeneration, cardiomyocyte dedifferentiation (with sarcomere disassembly) occurs as the first stage of proliferation and is triggered by hypoxia. [18,19] In humans, proliferation may stall due to persistent hypoxia or limited energetic substrate.…”