Skip to main content

Advertisement

Log in

Molecular pathology of natriuretic peptides in the myocardium with special regard to fatal intoxication, hypothermia, and hyperthermia

  • Original Article
  • Published:
International Journal of Legal Medicine Aims and scope Submit manuscript

Abstract

The present study investigated the molecular pathology of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium to evaluate terminal cardiac function in routine forensic casework with particular regard to fatal drug intoxication (n = 18; sedative–hypnotics, n = 10; methamphetamine, n = 8), hypothermia (cold exposure, n = 13), and hyperthermia (heatstroke, n = 10), compared with that in acute ischemic heart disease (AIHD, n = 35) and congestive heart disease (CHD, n = 11) as controls (total n = 87; within 48 h postmortem). Quantitative analyses of myocardial ANP and BNP messenger RNA demonstrated that their expressions in bilateral atrial and ventricular walls were high in methamphetamine intoxication and hypothermia, comparable to those in AIHD and CHD, but were low in sedative–hypnotic intoxication and hyperthermia. In pericardial fluid, both ANP and BNP levels were increased in hypothermia, while CHD cases had an elevated BNP level, and ANP level showed a tendency to increase in hyperthermia; however, immunohistochemistry showed no evident differences in myocardial ANP and BNP among the causes of death. These findings suggest terminal high cardiac strain in methamphetamine intoxication, decreased cardiac strain in sedative–hypnotic intoxication and hyperthermia (heatstroke), and persistent congestion in hypothermia (cold exposure).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Maeda H, Zhu BL, Ishikawa T et al (2010) Forensic molecular pathology of violent deaths. Forensic Sci Int 203:83–92

    Article  PubMed  CAS  Google Scholar 

  2. Zhao D, Zhu BL, Ishikawa T et al (2006) Real-time RT-PCR quantitative assays and postmortem degradation profiles of erythropoietin, vascular endothelial growth factor and hypoxia-inducible factor 1 alpha mRNA transcripts in forensic autopsy materials. Leg Med (Tokyo) 8:132–136

    Article  CAS  Google Scholar 

  3. Ishida K, Zhu BL, Maeda H (2000) Novel approach to quantitative reverse transcription PCR assay of mRNA component in autopsy material using the TaqMan fluorogenic detection system: dynamics of pulmonary surfactant apoprotein A. Forensic Sci Int 113:127–131

    Article  PubMed  CAS  Google Scholar 

  4. Bauer M (2007) RNA in forensic science. Forensic Sci Int Genet 1:69–74

    Article  PubMed  CAS  Google Scholar 

  5. Zhao D, Ishikawa T, Quan L et al (2009) Evaluation of pulmonary GLUT1 and VEGF mRNA levels in relation to lung weight in medicolegal autopsy cases. Leg Med (Tokyo) 11:S290–S293

    Article  Google Scholar 

  6. Mannix ET, Farber MO, Aronoff GR et al (1991) Regulation of atrial natriuretic peptide release in normal humans. J Appl Physiol 71:1340–1345

    PubMed  CAS  Google Scholar 

  7. de Bold AJ, Bruneau BG, Kuroski de Bold ML (1996) Mechanical and neuroendocrine regulation of the endocrine heart. Cardiovasc Res 31:7–18

    Article  PubMed  Google Scholar 

  8. LaPointe MC (2005) Molecular regulation of the brain natriuretic peptide gene. Peptides 26:944–956

    Article  PubMed  CAS  Google Scholar 

  9. McGrath MF, de Bold AJ (2005) Determinants of natriuretic peptide gene expression. Peptides 26:933–943

    Article  PubMed  CAS  Google Scholar 

  10. Tsokos M, Rothschild MA, Madea B et al (2006) Histological and immunohistochemical study of Wischnewsky spots in fatal hypothermia. Am J Forensic Med Pathol 27:70–74

    Article  PubMed  Google Scholar 

  11. Zhu BL, Ishikawa T, Michiue T et al (2007) Differences in postmortem urea nitrogen, creatinine and uric acid levels between blood and pericardial fluid in acute death. Leg Med (Tokyo) 9:115–122

    Article  CAS  Google Scholar 

  12. Mizukami H, Shimizu K, Shiono H et al (1999) Forensic diagnosis of death from cold. Leg Med (Tokyo) 1:204–209

    Article  CAS  Google Scholar 

  13. Zhu BL, Ishida K, Quan L et al (2001) Post-mortem urinary myoglobin levels with reference to the causes of death. Forensic Sci Int 115:183–188

    Article  PubMed  CAS  Google Scholar 

  14. Maeda H, Zhu BL, Bessho Y et al (2008) Postmortem serum nitrogen compounds and C-reactive protein levels with special regard to investigation of fatal hyperthermia. Forensic Sci Med Pathol 4:175–180

    Article  PubMed  CAS  Google Scholar 

  15. Bouchama A, Knochel JP (2002) Heat stroke. N Engl J Med 346:1978–1988

    Article  PubMed  CAS  Google Scholar 

  16. Zhu BL, Ishikawa T, Michiue T et al (2007) Postmortem pericardial natriuretic peptides as markers of cardiac function in medico-legal autopsies. Int J Legal Med 121:28–35

    Article  PubMed  Google Scholar 

  17. Ishida K, Zhu BL, Maeda H (2005) TaqMan fluorogenic detection system to analyze gene transcription in autopsy material. Methods Mol Biol 291:415–421

    Google Scholar 

  18. Ishida K, Zhu BL, Maeda H (2002) A quantitative RT-PCR assay of surfactant-associated protein A1 and A2 mRNA transcripts as a diagnostic tool for acute asphyxial death. Leg Med (Tokyo) 4:7–12

    Article  CAS  Google Scholar 

  19. Vandesompele J, De Preter K, Pattyn F et al (2002) Accurate normalization of real-time quantitative RT-PCR data by genometric averaging of multiple internal control genes. Genome Biol 3:1–11

    Article  Google Scholar 

  20. Zhu BL, Tanaka S, Ishikawa T et al (2008) Forensic pathological investigation of myocardial hypoxia-inducible factor-1 alpha, erythropoietin and vascular endothelial growth factor in cardiac death. Leg Med (Tokyo) 10:11–19

    Article  CAS  Google Scholar 

  21. Koppelkamm A, Vennemann B, Fracasso T et al (2010) Validation of adequate endogenous reference genes for the normalization of qPCR gene expression data in human post mortem tissue. Int J Legal Med 124:371–380

    Article  PubMed  Google Scholar 

  22. Chen JH, Michiue T, Ishikawa T et al (2012) Difference in molecular pathology of natriuretic peptides in the myocardium between acute asphyxial and cardiac deaths. Leg Med (Tokyo)14:177–182

    Google Scholar 

  23. Miyazato T, Ishikawa T, Michiue T et al (2012) Molecular pathology of pulmonary surfactants and cytokines in drowning compared with other asphyxiation and fatal hypothermia. Int J Legal Med 126:581–587

    Google Scholar 

  24. Preuss J, Dettmeyer R, Poster S et al (2008) The expression of heat shock protein 70 in kidneys in cases of death due to hypothermia. Forensic Sci Int 176:248–252

    Article  PubMed  CAS  Google Scholar 

  25. Ishikawa T, Yoshida C, Michiue T et al (2010) Immunohistochemistry of catecholamines in the hypothalamic-pituitary-adrenal system with special regard to fatal hypothermia and hyperthermia. Leg Med (Tokyo) 12:121–127

    Article  CAS  Google Scholar 

  26. Ishikawa T, Michiue T, Maeda H (2011) Evaluation of postmortem serum and cerebrospinal fluid growth hormone levels in relation to the cause of death in forensic autopsy. Hum Cell 24:74–77

    Article  PubMed  Google Scholar 

  27. Ishikawa T, Quan L, Li DR et al (2008) Postmortem biochemistry and immunohistochemistry of adrenocorticotropic hormone with special regard to fatal hypothermia. Forensic Sci Int 179:147–151

    Article  PubMed  CAS  Google Scholar 

  28. Ishikawa T, Miyaishi S, Tachibana T et al (2004) Fatal hypothermia related vacuolation of hormone-producing cells in the anterior pituitary. Leg Med (Tokyo) 6:157–163

    Article  CAS  Google Scholar 

  29. Yoshida C, Ishikawa T, Michiue T et al (2011) Postmortem biochemistry and immunohistochemistry of chromogranin A as a stress marker with special regard to fatal hypothermia and hyperthermia. Int J Legal Med 125:11–20

    Article  PubMed  Google Scholar 

  30. Quan L, Ishikawa T, Hara J et al (2011) Postmortem serotonin levels in cerebrospinal and pericardial fluids with regard to the cause of death in medicolegal autopsy. Leg Med (Tokyo) 13:75–78

    Article  CAS  Google Scholar 

  31. Wang Q, Michiue T, Ishikawa T et al (2011) Combined analyses of creatine kinase MB, cardiac troponin I and myoglobin in pericardial and cerebrospinal fluids to investigate myocardial and skeletal muscle injury in medicolegal autopsy cases. Leg Med (Tokyo) 13:226–232

    Article  CAS  Google Scholar 

  32. Quan L, Ishikawa T, Michiue T et al (2005) Ubiquitin-immunoreactive structures in the midbrain of methamphetamine abusers. Leg Med (Tokyo) 7:144–150

    Article  CAS  Google Scholar 

  33. Ishikawa T, Zhu BL, Miyaishi S et al (2007) Increase in clusterin-containing follicles in the adenohypophysis of drug abusers. Int J Legal Med 121:395–402

    Article  PubMed  Google Scholar 

  34. Zhu BL, Ishida K, Oritani S et al (2001) Immunohistochemical investigation of pulmonary surfactant-associated protein A in fatal poisoning. Forensic Sci Int 117:205–212

    Article  PubMed  CAS  Google Scholar 

  35. Potter LR (2011) Natriuretic peptide metabolism, clearance and degradation. FEBS J 278:1808–1817

    Article  PubMed  CAS  Google Scholar 

  36. Xu-Cai YO, Wu Q (2010) Molecular forms of natriuretic peptides in heart failure and their implications. Heart 96:419–424

    Google Scholar 

  37. Daniels LB, Maisel AS (2007) Natriuretic peptides. J Am Coll Cardiol 50:2357–2368

    Article  PubMed  CAS  Google Scholar 

  38. Hama N, Itoh H, Shirakami G et al (1995) Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction. Circulation 92:1558–1564

    Article  PubMed  CAS  Google Scholar 

  39. Pappas L, Filippatos G (2011) Pulmonary congestion in acute heart failure: from hemodynamics to lung injury and barrier dysfunction. Rev Esp Cardiol 64:735–738

    Article  PubMed  Google Scholar 

  40. Patel MM, Belson MG, Longwater AB et al (2005) Methylenedioxymethamphetamine (ecstasy)-related hyperthermia. J Emerg Med 29:451–454

    Article  Google Scholar 

  41. Freedman RR, Johanson CE, Tancer ME (2005) Thermoregulatory effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berl) 183:248–256

    Article  CAS  Google Scholar 

  42. Ferslew KE, Hagardorn AN, Harlan GC et al (1998) A fatal drug interaction between clozapine and fluoxetine. J Forensic Sci 43:1082–1085

    PubMed  CAS  Google Scholar 

  43. Iacovelli L, Fulceri F, De Blasi A et al (2006) The neurotoxicity of amphetamines: bridging drugs of abuse and neurodegenerative disorders. Exp Neurol 201:24–31

    Article  PubMed  CAS  Google Scholar 

  44. Turk EE (2010) Hypothermia. Forensic Sci Med Pathol 6:106–115

    Article  PubMed  Google Scholar 

  45. Aslam AF, Aslam AK, Vasavada BC et al (2006) Hypothermia: evaluation, electrocardiographic manifestations, and management. Am J Med 119:297–301

    Article  PubMed  Google Scholar 

  46. Wolfe CS (1993) Severe hypothermia associated with prolonged cardiorespiratory arrest and full recovery. J Am Board Fam Pract 6:594–596

    PubMed  CAS  Google Scholar 

  47. Broessner G, Beer R, Franz G et al (2005) Case report: severe heat stroke with multiple organ dysfunction - a novel intravascular treatment approach. Crit Care 9:R498–R501

    Article  PubMed  Google Scholar 

  48. Holman ND, Schneider AJ (1989) Multi-organ damage in exertional heat stroke. Neth J Med 35:38–43

    PubMed  CAS  Google Scholar 

  49. Ali SZ, Taguchi A, Rosenberg H et al (2003) Malignant hyperthermia. Best Pract Res Clin Anaesthesiol 17:519–533

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science and Technology, Japan (grant no. 22590642).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tomomi Michiue.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, JH., Michiue, T., Ishikawa, T. et al. Molecular pathology of natriuretic peptides in the myocardium with special regard to fatal intoxication, hypothermia, and hyperthermia. Int J Legal Med 126, 747–756 (2012). https://doi.org/10.1007/s00414-012-0732-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00414-012-0732-4

Keywords

Navigation