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Victims of lethal hypothermia have decreased levels of thrombomodulin in myocardium and urine

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Abstract

Severe cold stress has been shown to cause changes in the expression and secretion of thrombomodulin (TM), an endothelial protein regulating haemostasis and inflammation. To further evaluate TM as a cold stress indicator, relative TM mRNA and TM protein levels in the myocardium and the concentrations of TM in serum and urine were analysed in different causes of death (hypothermia main cause, n = 80; hypothermia contributory cause, n = 26; cardiovascular disease (CVD) main cause, n = 94; trauma main cause, n = 45; other main cause, n = 25). Urinary catecholamine concentrations and myocardial heat shock factor 1 (HSF1) transcript levels were also studied. The TM mRNA and the TM protein levels in myocardium and urine were significantly lower in hypothermia deaths than those in the controls. Post-mortem interval did not correlate with urinary TM concentration. The sensitivity and specificity of urinary TM assay to detect hypothermia deaths were 70.8 and 70.3 %, respectively. Catecholamine concentrations in urine correlated significantly with TM concentration in urine and TM mRNA levels in all groups excluding CVD deaths. There were no differences in the HSF1 transcript levels and no correlation to TM levels. These findings provide further evidence that cold stress and hypothermia affect TM expression and secretion and that they are possibly linked to catecholamine action. Thus, measuring post-mortem TM levels may provide additional support to diagnosing hypothermia in medico-legal examination. The results may also provide additional knowledge for the treatment of hypothermic patients and the use of hypothermia for medical purposes.

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Acknowledgments

The authors are grateful to the staff of the department and the laboratory for assisting in the sample collection and processing.

Ethical standards

The experiments of this study comply with the current Finnish laws. The study protocol was approved by the University of Oulu and Northern Ostrobothnia Hospital research ethics committee.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Diagnostics, Department of Forensic Medicine, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland

    Lasse Pakanen, Helena Kaija, Marja-Leena Kortelainen & Katja Porvari

  2. Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland

    Lasse Pakanen, Helena Kaija, Marja-Leena Kortelainen & Katja Porvari

  3. National Supervisory Authority for Welfare and Health, P.O. Box 210, FI-00531, Helsinki, Finland

    Terttu Särkioja

Authors
  1. Lasse Pakanen
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  2. Helena Kaija
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  3. Marja-Leena Kortelainen
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  4. Terttu Särkioja
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  5. Katja Porvari
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Correspondence to Katja Porvari.

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Pakanen, L., Kaija, H., Kortelainen, ML. et al. Victims of lethal hypothermia have decreased levels of thrombomodulin in myocardium and urine. Int J Legal Med 129, 289–296 (2015). https://doi.org/10.1007/s00414-014-1138-2

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  • DOI: https://doi.org/10.1007/s00414-014-1138-2

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