Chronic ischemic viable myocardium in man: Aspects of dedifferentiation

Temporal and Spatial Variations in Structural Protein Expression During the Progression From Stunned to Hibernating Myocardium

“…Myocardial hibernation in humans and animal models results in characteristic ultrastructural changes in cardiomyocytes, consisting of myolysis and subsequent glycogen accumulation in the myolytic areas. 1,4,8,20 Whereas these changes have been believed to reflect an adaptive response of the heart to ischemia, similar observations have been made in cardiac tissue after atrial fibrillation and mitral valve disease. 21,22 In addition to these ultrastructural changes, hibernating myocardium is accompanied by changes in the distribution of structural proteins.…”

“…Loss of cardiotin expression, disorganized expression of desmin in the cytoplasm, loss of desmin at the intercalated disks, loss of titin double striations, and reexpression of ␣-SM actin have all been described in humans with chronic hibernating myocardium. 1,10 Surprisingly, the extent of alterations in structural protein expression was similar in both regions of the heart after 2 weeks of impaired flow. Thus, like the observations by Thomas and coworkers 8 on myolysis, glycogen accumulation, and electron microscopic changes, the hibernating myocyte phenotype cannot be directly attributed to an adaptive response arising from a regional alteration in myocardial perfusion.…”

“…These alterations have been hypothesized to be an adaptive response to ischemic stress through cardiomyocyte dedifferentiation. 1,23 Previous interpretations in humans have, with 1 exception, 24 been limited by the absence of control samples from remote nondysfunctional myocardium. Thomas et al 8 found myolysis and glycogen accumulation to be independent of regional flow differences in swine with hibernating myocardium, indicating that ultrastructural adaptations were dissociated from regional ischemia.…”

“…[1][2][3][4] It has been hypothesized that these alterations represent an intrinsic adaptive response to a metabolic imbalance 5,6 because of the absence of morphological and cytochemical characteristics of acute ischemia. 6,7 In swine, the transition from chronically stunned to hibernating myocardium is preceded by progressive alterations in the degree of myolysis and regional reductions in the expression of sarcoplasmic reticulum proteins.…”

Regulation of intercellular coupling in acute and chronic heart disease

“…The morphological picture of the myocyte survival response is nonspecific. The same structural changes occur in response to diverse forms of sub-lethal injury and include partial or nearly complete loss of sarcomeres, accumulation of glycogen and disorganization and loss of sarcoplasmic reticulum (13)(14)(15), as well as a reduction in gap junction protein expression and loss of large gap junctions (16)(17)(18). These stereotypical morphological changes, referred to as myocytolysis, are universally observed, at least to some extent, in dysfunctional ventricular wall segments in patients with chronic ischemic heart disease (18) and in diverse forms of cardiomyopathy in patients with heart failure (13-15,19).…”