Revision of the troponin T release mechanism from damaged human myocardium.
BACKGROUND
Cardiac troponin T (cTnT) is released from damaged heart tissue in patients with acute myocardial infarction. It is presumed that most cTnT is tightly bound and released following the degradation of myofibrils in necrotic cardiomyocytes, resulting in sustained increases in circulating cTnT. Evidence of a large irreversibly bound fraction is based on the inability to extract most cTnT from cardiac tissue in cold low-salt extraction buffers.


METHODS
Here we examined in vitro extraction of cTnT from human cardiac tissue in serum at 37 °C.


RESULTS
We found that over 80% of the cTnT can be extracted from human cardiac tissue in 90 min using large volumes of human serum at 37 °C. The release ratio was highly dependent on the extraction volume and was only 3% if an equal volume of serum and heart tissue was used. In contrast, extraction of the cytoplasmic cardiac damage markers myoglobin and creatinine kinase was much less affected by changing these conditions. Purified cTnT was poorly soluble in a low-salt extraction buffer at 0 °C, previously used to define the free cTnT fraction.


CONCLUSIONS
Our data indicate that the diffusible fraction of cTnT is likely substantially larger in vivo than previously reported and likely is not fixed but dependent on local plasma flow. It is therefore possible that the sustained increase in circulating cTnT after myocardial infarction is at least in part due to a slow washout of cTnT that interacts reversibly with tropomyosin in myofibrils.
Department of Clinical Chemistry and Transfusion Medicine and.
Karin
K
Starnberg
Department of Cardiothoracic Surgery, Sahlgrenska University Hospital Gothenburg, Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;
Anders
A
Jeppsson
Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Bertil
B
Lindahl
Department of Clinical Chemistry and Transfusion Medicine and ola.hammarsten@clinchem.gu.se.
Ola
O
Hammarsten
D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D001706:Biopsy; D006801:Humans; D057230:Limit of Detection; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020107:Troponin T / Q000097:blood / Q000378:metabolism*
D015415:Biomarkers; D020107:Troponin T