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(Circulation. 2000;102:1221.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Extensive Troponin I and T Modification Detected in Serum From Patients With Acute Myocardial Infarction
From the Departments of Physiology (R.L., L.O., J.E.V.E.), Biochemistry (J.E.V.E.), and Pathology (C.C.), Queen’s University, Kingston, Ontario, Canada; Cardiovascular Research, Institute of Physiology, University of Zurich, Zurich, Switzerland (R.L.); and the Heart Center, Division of Cardiology, State University Hospital, Copenhagen, Denmark (D.A.).
Correspondence to Dr Jennifer E. Van Eyk, Department of Physiology, Queen’s University, Kingston, Ontario, Canada K7L 3N6. E-mail JVE1{at}post.queensu.ca
Background—Cardiac troponin I and
T (cTnI and cTnT) are specific biochemical serum markers for acute
myocardial infarction (AMI). However, cTnI diagnostic
assays are plagued by difficulties, resulting in 
20-fold differences
in measured values. These discrepancies may result from the release of
the numerous cTnI modification products that are present in
ischemic myocardium. The resolution of these
discrepancies requires an investigation of the exact forms of cTnI
present in the bloodstream of patients after myocardial
injury.
Methods and Results—A western blot–direct serum analysis protocol was developed that allowed us to detect intact cTnI and a spectrum of up to 11 modified products in the serum from patients with AMI. For the first time, we document both a cTnI degradation pattern and the existence of phosphorylated cTnI in serum. The number and extent of these modifications reflect patterns similar to the time profiles of the routine clinical serum markers of total creatine kinase, creatine kinase-MB, and cTnI (determined by ELISA). Data from in vitro experiments, which were undertaken to study the degradation of human recombinant cTnI and cTnT when spiked in serum, indicate that some modification products present in patient serum existed in the myocardium and that recombinant cTnI alteration dramatically reduces the detectability of cTnI by the Immuno1 assay over time (our assay was unaffected).
Conclusions—This pilot study defines, for the first time, what forms of cTnI and cTnT appear in the bloodstream of AMI patients, and it clarifies the lack of standardization between different cTnI diagnostic assays.
Key Words: troponin • myocardial infarction • biological markers • diagnosis • blotting, western
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