Forensic Science, Medicine, and Pathology

, Volume 10, Issue 3, pp 395–400 | Cite as

Can early myocardial infarction-related deaths be diagnosed using postmortem urotensin receptor expression levels?

  • Mustafa Talip Sener
  • Emre Karakus
  • Zekai Halici
  • Erol Akpinar
  • Atilla Topcu
  • Ahmet Nezih Kok
Original Article



Myocardial infarction (MI) is one of the most prevalent causes of sudden adult death. It is difficult to diagnose early MI postmortem because there are no typical or characteristic changes in morphology. In this study, changes in the level of the mRNA for the urotensin receptor (UR) were investigated postmortem to determine the suitability of UR as a biomarker for diagnosis of early MI after death.


An MI rat model was developed by injecting rats with isoproterenol (ISO) (lethal dose 850 mg/kg) or normal saline (control group). The hearts of rats in the control and ISO-induced MI groups were harvested at 0, 1, 3, 6, 12, 24, 48, and 72 h (h) postmortem. The hearts were then immediately submerged in 1 mL of RNA stabilization solution and stored at 4 °C for <1 week before RNA extraction. Relative UR expression analysis was performed using the StepOne Plus Real Time PCR System with cDNA synthesized from rat heart.


Postmortem UR mRNA expression was higher in the ISO-induced MI group than in the control group, at both 4 and 20 °C, at all of the time points examined except 72 h postmortem (p < 0.0001). The largest increases were observed at ambient temperature and 6 h postmortem.


Based on our findings, increased postmortem UR expression could serve as a biomarker to aid diagnosis of early MI.


Myocardial infarction Urotensin receptor Sudden death Rats 


  1. 1.
    Adnet F, Renault R, Jabre P, Kulstad E, Galinski M, Lapostolle F. Incidence of acute myocardial infarction resulting in sudden death outside the hospital. Emerg Med J. 2011;28:884–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Rodriguez-Calvo MS, Brion M, Allegue C, Concheiro L, Carracedo A. Molecular genetics of sudden cardiac death. Forensic Sci Int. 2008;182:1–12.PubMedCrossRefGoogle Scholar
  3. 3.
    Kakimoto Y, Tsuruyama T, Miyao M, Abiru H, Sumiyoshi S, Kotani H, Haga H, Tamaki K. The effectiveness and limitations of triphenyltetrazolium chloride to detect acute myocardial infarction at forensic autopsy. Am J Forensic Med Pathol. 2013;34:242–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Perez-Carceles MD, Noguera J, Jimenez JL, Martinez P, Luna A, Osuna E. Diagnostic efficacy of biochemical markers in diagnosis post-mortem of ischaemic heart disease. Forensic Sci Int. 2004;142:1–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Batalis NI, Marcus BJ, Papadea CN, Collins KA. The role of postmortem cardiac markers in the diagnosis of acute myocardial infarction. J Forensic Sci. 2010;55:1088–91.PubMedCrossRefGoogle Scholar
  6. 6.
    Osuna E, Perez-Carceles MD, Alvarez MV, Noguera J, Luna A. Cardiac troponin I (cTn I) and the postmortem diagnosis of myocardial infarction. Int J Legal Med. 1998;111:173–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Bi H, Yang Y, Huang J, Li Y, Ma C, Cong B. Immunohistochemical detection of S100A1 in the postmortem diagnosis of acute myocardial infarction. Diagn Pathol. 2013;8:84.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Bardales RH, Hailey LS, Xie SS, Schaefer RF, Hsu SM. In situ apoptosis assay for the detection of early acute myocardial infarction. Am J Pathol. 1996;149:821–9.PubMedCentralPubMedGoogle Scholar
  9. 9.
    Rodriguez-Calvo MS, Tourret MN, Concheiro L, Munoz JI, Suarez-Penaranda JM. Detection of apoptosis in ischemic heart. Usefulness in the diagnosis of early myocardial injury. Am J Forensic Med Pathol. 2001;22:278–84.PubMedCrossRefGoogle Scholar
  10. 10.
    Domenech P, Carbonell L, Perez Carceles MD, Falcon M, Luna A, Osuna E. Application of postmortem lipid peroxidation in heart tissue to the diagnosis of myocardial damage. Int J Legal Med. 2004;118:19–23.PubMedCrossRefGoogle Scholar
  11. 11.
    Jasra SK, Badian C, Macri I, Ra P. Recognition of early myocardial infarction by immunohistochemical staining with cardiac troponin-I and complement C9. J Forensic Sci. 2012;57:1595–600.PubMedCrossRefGoogle Scholar
  12. 12.
    Leadbeatter S, Wawman HM, Jasani B. Immunocytochemical diagnosis of early myocardial ischaemic/hypoxic damage. Forensic Sci Int. 1989;40:171–80.PubMedCrossRefGoogle Scholar
  13. 13.
    Ortmann C, Pfeiffer H, Brinkmann B. A comparative study on the immunohistochemical detection of early myocardial damage. Int J Legal Med. 2000;113:215–20.PubMedCrossRefGoogle Scholar
  14. 14.
    Piercecchi-Marti MD, Lepidi H, Leonetti G, Vire O, Cianfarani F, Pellissier JF. Immunostaining by complement C9: a tool for early diagnosis of myocardial infarction and application in forensic medicine. J Forensic Sci. 2001;46:328–34.PubMedGoogle Scholar
  15. 15.
    Ribeiro-Silva A, Rossi MA, Martin CC. Is immunohistochemistry a useful tool in the postmortem recognition of myocardial hypoxia in human tissue with no morphological evidence of necrosis? Am J Forensic Med Pathol. 2002;23:72–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Lewandrowski KB. Cardiac markers of myocardial necrosis: a history and discussion of milestones and emerging new trends. Clin Lab Med. 2014;34:31–41.PubMedCrossRefGoogle Scholar
  17. 17.
    Kost GJ, Kirk JD, Omand K. A strategy for the use of cardiac injury markers (troponin I and T, creatine kinase-MB mass and isoforms, and myoglobin) in the diagnosis of acute myocardial infarction. Arch Pathol Lab Med. 1998;122:245–51.PubMedGoogle Scholar
  18. 18.
    Hansen SH, Rossen K. Evaluation of cardiac troponin I immunoreaction in autopsy hearts: a possible marker of early myocardial infarction. Forensic Sci Int. 1999;99:189–96.PubMedCrossRefGoogle Scholar
  19. 19.
    Sapouna R, Gourgiotis D, Athanaselis S, Papadodima S, Spiliopoulou C. Diagnostic value of cardiac troponin I in postmortem diagnosis of myocardial infarction. Am J Forensic Med Pathol. 2013;34:139–41.PubMedCrossRefGoogle Scholar
  20. 20.
    Hu BJ, Chen YC, Zhu JZ. Study on the specificity of fibronectin for post-mortem diagnosis of early myocardial infarction. Med Sci Law. 2002;42:195–9.PubMedGoogle Scholar
  21. 21.
    Lachica E, Villanueva E, Luna A. Comparison of different techniques for the postmortem diagnosis of myocardial infarction. Forensic Sci Int. 1988;38:21–6.PubMedCrossRefGoogle Scholar
  22. 22.
    de la Grandmaison GL. Is there progress in the autopsy diagnosis of sudden unexpected death in adults? Forensic Sci Int. 2006;156:138–44.PubMedCrossRefGoogle Scholar
  23. 23.
    Langham RG, Kelly DJ, Gow RM, Zhang Y, Dowling JK, Thomson NM, Gilbert RE. Increased expression of urotensin II and urotensin II receptor in human diabetic nephropathy. Am J Kidney Dis. 2004;44:826–31.PubMedCrossRefGoogle Scholar
  24. 24.
    Clozel M, Binkert C, Birker-Robaczewska M, Boukhadra C, Ding SS, Fischli W, et al. Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin System. J Pharmacol Exp Ther. 2004;311:204–12.PubMedCrossRefGoogle Scholar
  25. 25.
    Protopopov A, Kashuba V, Podowski R, Gizatullin R, Sonnhammer E, Wahlestedt C, et al. Assignment of the GPR14 gene coding for the G-protein-coupled receptor 14 to human chromosome 17q25.3 by fluorescent in situ hybridization. Cytogenet Cell Genet. 2000;88:312–3.PubMedCrossRefGoogle Scholar
  26. 26.
    Ames RS, Sarau HM, Chambers JK, Willette RN, Aiyar NV, Romanic AM, et al. Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature. 1999;401:282–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Zhu YC, Zhu YZ, Moore PK. The role of urotensin II in cardiovascular and renal physiology and diseases. Br J Pharmacol. 2006;148:884–901.PubMedCentralPubMedGoogle Scholar
  28. 28.
    Douglas SA, Tayara L, Ohlstein EH, Halawa N, Giaid A. Congestive heart failure and expression of myocardial urotensin II. Lancet. 2002;359:1990–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Khan SQ, Bhandari SS, Quinn P, Davies JE, Ng LL. Urotensin II is raised in acute myocardial infarction and low levels predict risk of adverse clinical outcome in humans. Int J Cardiol. 2007;117:323–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Zhang YG, Li J, Li YG, Wei RH. Urotensin II induces phenotypic differentiation, migration, and collagen synthesis of adventitial fibroblasts from rat aorta. J Hypertens. 2008;26:1119–26.PubMedCrossRefGoogle Scholar
  31. 31.
    Tzanidis A, Hannan RD, Thomas WG, Onan D, Autelitano DJ, See F, Kelly DJ, Gilbert RE, Krum H. Direct actions of urotensin II on the heart: implications for cardiac fibrosis and hypertrophy. Circ Res. 2003;93:246–53.PubMedCrossRefGoogle Scholar
  32. 32.
    Pakala R. Role of urotensin II in atherosclerotic cardiovascular diseases. Cardiovasc Revasc Med. 2008;9:166–78.PubMedCrossRefGoogle Scholar
  33. 33.
    Chappel CI, Rona G, Balazs T, Gaudry R. Severe myocardial necrosis produced by isoproterenol in the rat. Arch Int Pharmacodyn Ther. 1959;122:123–8.PubMedGoogle Scholar
  34. 34.
    Sharma M, Kishore K, Gupta SK, Joshi S, Arya DS. Cardioprotective potential of ocimum sanctum in isoproterenol induced myocardial infarction in rats. Mol Cell Biochem. 2001;225:75–83.PubMedCrossRefGoogle Scholar
  35. 35.
    Kralova E, Mokran T, Murin J, Stankovicova T. Electrocardiography in two models of isoproterenol-induced left ventricular remodeling. Physiol Res. 2008;57:83–9.Google Scholar
  36. 36.
    Ojha S, Goyal S, Sharma C, Arora S, Kumari S, Arya DS. Cardioprotective effect of lycopene against isoproterenol-induced myocardial infarction in rats. Hum Exp Toxicol. 2013;32:492–503.PubMedCrossRefGoogle Scholar
  37. 37.
    Mao S, Fu G, Seese RR, Wang ZY. Estimation of PMI depends on the changes in ATP and its degradation products. Legal Med (Tokyo). 2013;15:235–8.CrossRefGoogle Scholar
  38. 38.
    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Jegou S, Cartier D, Dubessy C, Gonzalez BJ, Chatenet D, Tostivint H, Scalbert E, LePrince J, Vaudry H, Lihrmann I. Localization of the urotensin II receptor in the rat central nervous system. J Comp Neurol. 2006;495:21–36.PubMedCrossRefGoogle Scholar
  40. 40.
    Vennemann M, Koppelkamm A. mRNA profiling in forensic genetics I: Possibilities and limitations. Forensic Sci Int. 2010;203:71–5.PubMedCrossRefGoogle Scholar
  41. 41.
    Harrison PJ, Heath PR, Eastwood SL, Burnet PWJ, McDonald B, Pearson RCA. The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: Selective mRNA vulnerability and comparison with their encoded proteins. Neurosci Lett. 1995;200:151–4.PubMedCrossRefGoogle Scholar
  42. 42.
    Li JZ, Vawter MP, Walsh DM, Tomita H, Evans SJ, Choudary PV, et al. Systematic changes in gene expression in postmortem human brains associated with tissue pH and terminal medical conditions. Hum Mol Genet. 2004;13:609–16.PubMedCrossRefGoogle Scholar
  43. 43.
    Preece P, Cairns NJ. Quantifying mRNA in postmortem human brain: influence of gender, age at death, postmortem interval, brain pH, agonal state and inter-lobe mRNA variance. Mol Brain Res. 2003;118:60–71.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Mustafa Talip Sener
    • 1
  • Emre Karakus
    • 2
  • Zekai Halici
    • 3
  • Erol Akpinar
    • 3
  • Atilla Topcu
    • 3
  • Ahmet Nezih Kok
    • 1
  1. 1.Department of Forensic MedicineAtaturk University School of MedicineErzurumTurkey
  2. 2.Department of Pharmacology and ToxicologyAtaturk University School of VeterinaryErzurumTurkey
  3. 3.Department of PharmacologyAtaturk University School of MedicineErzurumTurkey

Personalised recommendations