Over 80% of cardiac troponin T can be extracted from human cardiac tissue in 90 minutes using large volumes of human serum at 37 °C, suggesting the diffusible fraction is larger than previously reported.
The diffusible fraction of cTnT from damaged myocardium is likely much larger than previously thought and dependent on local plasma flow, revising the understanding of troponin release kinetics post-MI.
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.
Starnberg et al. (2014) studied Acute myocardial infarction. In vitro extraction in human serum at 37 °C vs. Extraction in cold low-salt extraction buffers at 0 °C was evaluated on Extraction of cTnT from human cardiac tissue. Over 80% of cardiac troponin T can be extracted from human cardiac tissue in 90 minutes using large volumes of human serum at 37 °C, suggesting the diffusible fraction is larger than previously reported.