Distribution of calcium in a subset of chronic hibernating myocardium in man

Abstract

The structural correlates of 'chronic hibernating myocardium' in man consist of myocardial cells which transformed from a functional state (rich in contractile material) to a surviving state (poor in contractile material, rich in glycogen). Since the calcium-handling organelles such as SR, sarcolemma and mitochondria underwent structural changes in cells so affected, the distribution of calcium was investigated in biopsies obtained from 'hibernating' areas. The material was processed for microscopic localization of total calcium (laser microprobe mass analysis, LAMMA) and of exchangeable calcium (phosphate-pyroantimonate precipitation method, PPA). Subcellular distribution of total calcium as assessed by LAMMA revealed that in the structurally affected cells the areas in which sarcomeres were replaced by glycogen contained significantly more calcium than all other areas probed such as mitochondria, remaining sarcomeres at the cell periphery and subcellular areas of normally structured cells. Calcium precipitate, obtained after PPA assessment, was localized at the sarcolemma but was virtually absent in the mitochondria of affected cells. The high calcium content in the myolytic areas of affected cells most probably belongs to a pool of bound calcium. The observations that calcium is retained at the sarcolemma and that mitochondria are devoid of precipitate favour the hypothesis that cells structurally affected as such are not ischaemic and are still able to regulate their calcium homeostasis.

Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning

“…On the other hand, the hibernating myocardium (136, 137) was first discovered by imaging methods in humans, and it was originally defined as "resting LV dysfunction due to reduced coronary blood flow that can be partially or completely reversed by myocardial revascularization and/or by reducing myocardial oxygen demand" (136). The concept was refined when ultrastructural investigations showed a distinctive morphology for hibernating myocardium, generally without necrosis, but with loss of sarcomeres and myofibrils (suggesting a "dedifferentiation" process toward an embryonic phenotype), with loss of mitochondria and increased glycogen storage (9,19,27,162).…”

“…On the other hand, the hibernating myocardium (136, 137) was first discovered by imaging methods in humans, and it was originally defined as "resting LV dysfunction due to reduced coronary blood flow that can be partially or completely reversed by myocardial revascularization and/or by reducing myocardial oxygen demand" (136). The concept was refined when ultrastructural investigations showed a distinctive morphology for hibernating myocardium, generally without necrosis, but with loss of sarcomeres and myofibrils (suggesting a "dedifferentiation" process toward an embryonic phenotype), with loss of mitochondria and increased glycogen storage (9,19,27,162).The clinical recognition that reperfusion could improve mechanical performance of an unscarred dysfunctional ischemic region of the myocardium was motivation for the study of so-called myocardial viability. Clinical interest in the issue in terms of management has been widely recognized: if myocardial hibernation or stunning occurs, reperfusion may positively impact not only local, but also overall, myocardial function, heart failure symptoms, and survival.…”

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

“…[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. 8,9 Surprisingly, the degree of myolysis and glycogen accumulation in the ischemic regions was identical to that in normally perfused remote regions.…”

Noninvasive Imaging of Myocardial Viability

“…9 Histopathological features of hibernating myocardium are profound but potentially reversible. 26,27 A substantial proportion of cardiac myocytes has sarcolemmal loss, but this is not accompanied by reduced cell volume. Instead, there is replacement by glycogen.…”