Human Hibernating Myocardium-Development to Degeneration

Summary

The term hibernating myocardium applies to regional left ventricular dysfunction caused by chronic ischemia. It has been postulated that this phenomenon represents a functional adaptation to the chronic lack of oxygen but our own morphological-clinical studies are in contrast to this hypothesis. Recently, we described in human hibernating myocardium a self-perpetuating continuous vicious circle of cellular degeneration, which leads to progressive tissue damage. Here, we put forward the assumption that this vicious circle of structural deterioration is initiated by a disturbed steady state between myocardial oxygen supply and demand followed by intracellular degenerative processes and extracellular repair mechanisms. Structural alterations of cardiomyocytes characterized by a reduced rate of protein synthesis and predominating degradation induce sequestration of cellular particles into the interstitial space accompanied by atrophy of cardiomyocytes. Consecutively, repair mechanisms in the extracellular matrix are initiated. During the inflammatory and fibrogenic phases of this reaction, replacement fibrosis is synthesized leading to a reduction of cell-cell-contacts and of intra- and extracellular coupling followed by derangement of mechanical and signal transduction. Due to the increasing degree of replacement fibrosis, microvascular density is reduced while the oxygen diffusion distance is increased until the oxygen supply to the cardiomyocytes becomes critical resulting in a further progression of intracellular degeneration. For this reason, we propose that this vicious circle is a self-perpetuating process of tissue injury leading to further reduction of regional left ventricular function. This circle can only be interrupted by restoration of an adequate myocardial perfusion.