title: Victims of lethal hypothermia have decreased levels of thrombomodulin in myocardium and urine.
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.
authors.affiliation: Institute of Diagnostics, Department of Forensic Medicine, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.
authors.forename: Lasse
authors.initials: L
authors.lastname: Pakanen
authors.forename: Helena
authors.initials: H
authors.lastname: Kaija
authors.forename: Marja-Leena
authors.initials: ML
authors.lastname: Kortelainen
authors.forename: Terttu
authors.initials: T
authors.lastname: Särkioja
authors.forename: Katja
authors.initials: K
authors.lastname: Porvari
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000378:metabolism; D016022:Case-Control Studies; D002395:Catecholamines / Q000652:urine; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D049429:Forensic Pathology; D000076249:Heat Shock Transcription Factors; D006801:Humans; D007035:Hypothermia / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012680:Sensitivity and Specificity; D018180:Thrombomodulin / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014947:Wounds and Injuries / Q000378:metabolism
chemical_list: D002395:Catecholamines; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D012333:RNA, Messenger; D018180:Thrombomodulin; D014157:Transcription Factors