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Quantifying the Release of Biomarkers of Myocardial Necrosis from Cardiac Myocytes and Intact Myocardium

Research output: Contribution to journalArticlepeer-review

Jack Marjot, Thomas E. Kaier, Eva D. Martin, Shiney S. Reji, O'Neal Copeland, Mohammed Iqbal, Bob Goodson, Sarah Hamren, Sian E. Harding, Michael S. Marber

Original languageEnglish
Pages (from-to)990–996
JournalClinical Chemistry
Volume63
Issue number5
Early online date4 Apr 2017
DOIs
Accepted/In press6 Jan 2017
E-pub ahead of print4 Apr 2017
Published1 May 2017

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Abstract

BACKGROUND: Myocardial infarction is diagnosed when biomarkers of cardiac necrosis exceed the 99th centile, although guidelines advocate even lower concentrations for early rule-out. We examined how many myocytes and how much myocardium these concentrations represent. We also examined if dietary troponin can confound the rule-out algorithm.

METHODS: Individual rat cardiac myocytes, rat myocar- dium, ovine myocardium, or human myocardium were spiked into 400- L aliquots of human serum. Blood was drawn from a volunteer after ingestion of ovine myocar- dium. High-sensitivity assays were used to measure car- diac troponin T (cTnT; Roche, Elecsys), cTnI (Abbott, Architect), and cardiac myosin-binding protein C (cMyC; EMD Millipore, Erenna®).

RESULTS: The cMyC assay could only detect the human protein. For each rat cardiac myocyte added to 400 L of human serum, cTnT and cTnI increased by 19.0 ng/L (95% CI, 16.8–21.2) and 18.9 ng/L (95% CI, 14.7– 23.1), respectively. Under identical conditions cTnT, cTnI, and cMyC increased by 3.9 ng/L (95% CI, 3.6– 4.3), 4.3 ng/L (95% CI, 3.8 – 4.7), and 41.0 ng/L (95% CI, 38.0–44.0) per g of human myocardium. There was no detectable change in cTnI or cTnT concentration after ingestion of sufficient ovine myocardium to increase cTnT and cTnI to approximately 1 108 times their lower limits of quantification.

CONCLUSIONS: Based on pragmatic assumptions regard- ing cTn and cMyC release efficiency, circulating species, and volume of distribution, 99th centile concentrations may be exceeded by necrosis of 40 mg of myocardium. This volume is much too small to detect by noninvasive imaging.

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