Troponin Release—Reversible or Irreversible Injury? Should We Care?

Controversies concerning whether cardiac biomarkers can be released in the absence of cell death have existed for years. The initial observations were made with lactate dehydrogenase (LDH),3 the 134-kDa enzyme that was found to be released from cells or organs in response to tissue injury in the absence of overt cell death (1). Similar issues arose with creatine kinase (CK) and CK isoenzyme MB (CK-MB). Heyndrickx et al. (2), who found increases in CK in response to brief (5–15 min) coronary occlusions thought to be insufficient to induce cardiac injury, argued that the release was due to ischemia and not cell death; however, pathologic confirmation of this finding was not demonstrated. Subsequently, Ishikawa et al. attempted to cause CK release in animals in the absence of cell death by creating small, graded coronary occlusions (3). Whenever they found CK release in the circulation, they observed cells that appeared severely damaged and necrotic, according to electron microscopy results and extensive evaluations of the potentially ischemic area. These findings were supported by the absence of mitochondrial CK in the blood, a biomarker that would provide clear evidence of irreversible cell death. For these reasons, this group argued that the release of CK (86 kDa) was due to cell death. The discussion has been extensive regarding this controversial issue of whether biomarkers can be released from cells in the absence of cell death. Initially, it was thought that regeneration of cardiac myocytes did not occur. That led to a real concern that if the release of biomarkers was due to cell death, one could in essence run out of heart tissue over time. That possibility is no longer a concern, because we now know that cardiomyocytes can regenerate and repair the heart (4). This controversy became topical again with the advent …