Release of cardiac troponin from healthy and damaged myocardium

Abstract

Cardiac troponins T and I are proteins released into serum after cardiac injury, and are the standard biomarkers for patients presenting to the emergency department with a suspicion of acute myocardial infarction (AMI). Cardiac troponin that appears in blood within a few hours is due to release from the cytosolic pool. A sustained irreversible release over the ensuing days is due to the degradation of the myofibrils, although recent data have challenged this concept. The analytical sensitivity for troponin assays have significantly improved since the initial release of commercial troponin assays over 20 years ago. As a result, the specificity of troponin for AMI has steadily declined, with abnormal concentrations seen in many non-cardiac diseases such as renal failure, sepsis, pulmonary embolism, and cardiac injury after chemotherapy such as with trastuzumab and doxorubicin. There are many theories as to how troponin is released into blood from patients with reversible myocardial ischemia and from patients with cardiac damage that is not related to ischemia. These theories include release of free subunit release through bleb formation, transient imbalance of oxygen supply and demand such as what occurs with acute vasospasm of coronary vessels, pulmonary embolism with right heart damage, apoptosis, acute cardiac stress leading to release of catecholamines and integrins, myocardial stretching, inflammation, and release of degraded troponin peptides. The mechanisms for these etiologies are reviewed.