The Complete Pharmacokinetic Profile of Serum Cardiac Troponin I in the Rat and the Dog

Dunn, Michael E.; Coluccio, Denise; Hirkaler, Gerard; Mikaelian, Igor; Nicklaus, Rosemary; Lipshultz, Steven E.; Doessegger, Lucette; Reddy, Micaela B.; Singer, Thomas P.; Geng, Wanping

doi:10.1093/toxsci/kfr190

Cited by 41 publications

(43 citation statements)

References 24 publications

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“…Four of five children with elevated cTnI, who also had cTnT measured (level of detection=0.01 ng/mL or 10 pg/mL), had highly elevated cTnT levels in the range seen in adults with unstable angina or myocardial infarction. Previously, it had been shown that cTnI accurately shows myocardial injury similar to cTnT [50,51]. Compared to the previous report of cardiac troponin levels in non-HIV or ART exposed children in an outpatient setting [9], the HEU children described in this current report had reassuringly lower rates of active myocardial injury as defined by serum cardiac troponin concentrations.…”

Section: Discussionmentioning

confidence: 43%

Cardiac biomarkers in HIV-exposed uninfected children

Wilkinson

Williams

Leister

et al. 2013

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Objectives To evaluate associations of cardiac biomarkers with in utero antiretroviral (ARV) drug exposures and cardiac function/structure measured by echocardiograms in HIV-exposed but uninfected (HEU) children. Design and methods We analyzed the association of three cardiac biomarkers (cardiac troponin T, cTnT; high sensitivity C-reactive protein, hsCRP; and N-terminal pro-brain natriuretic peptide, NT-proBNP) with prenatal ARV exposures, maternal-child characteristics, and echocardiographic parameters. Results Among 338 HEU children (mean age=4.3 years), 51% had at least 1 elevated cardiac biomarker. Maternal tobacco use was associated with elevated NT-proBNP (adjusted odds ratio [aOR]=2.28, P=0.02). Maternal alcohol and abacavir use were associated with elevated cTnT levels (aOR=3.56, P=0.01 and aOR=2.33, P=0.04, respectively). Among 94 children with paired echocardiogram-biomarker measurements, cTnT measurements were correlated with increased left ventricular (LV) thickness-to-dimension ratio (r=0.21, P=0.04); and elevated cTnT was associated with higher mean LV end-diastolic (ED) posterior wall thickness (P=0.04). hsCRP measurements were negatively correlated with septal thickness (r=-0.22, P=0.03) and elevated hsCRP was associated with lower mean LV contractility Z-scores (P=0.04). NT-proBNP measurements were correlated with increased LVED dimension (r=0.20, P=0.05) and elevated NT-proBNP was associated with lower mean end-systolic septal thickness (P=0.03). Conclusion Our findings suggest that cardiac biomarkers may help identify HEU children who require further cardiac evaluation including echocardiography. Potential cardiac effects of prenatal abacavir exposure in this population need further investigation.

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Section: Discussionmentioning

confidence: 43%

Cardiac biomarkers in HIV-exposed uninfected children

Wilkinson

Williams

Leister

et al. 2013

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“…The half-lives of cTnT (5,9 ), CKMB (10,11 ), and Myo (12,13 ) are not substantially different once they reach the circulation. The sustained cTnT increase observed following an AMI is therefore likely due to a delayed release from the damaged myocardium (6 ).…”

confidence: 94%

Revision of the Troponin T Release Mechanism from Damaged Human Myocardium

Starnberg¹,

Jeppsson

Lindahl

et al. 2014

Clinical Chemistry

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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.

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“…Although most individuals have shown the post-exercise cTn peak at 3 h, i.e. after the reported half-lives of cTns (in the order of a couple of hours), there is some interindividual variation [12,16,17]. It has additionally been suspected that the time course may be dependent upon type of physical activity.…”

Section: Assaymentioning

confidence: 99%