Advertisement

International Journal of Legal Medicine

, Volume 133, Issue 2, pp 529–538 | Cite as

The impact of sex and myocardial ischemic preconditioning on immunohistochemical markers of acute myocardial infarction

  • K. Scholl
  • R. Huhn
  • St. Ritz-Timme
  • F. MayerEmail author
Original Article

Abstract

The immunohistochemical detection of dityrosine, troponins I (cTNI) and T (cTnT), and connexin 43 has been proposed as a tool for the diagnosis of myocardial infarction with short survival times. Results of clinical and experimental studies reveal that gender and/or ischemic preconditioning of the heart may have an influence on severity and magnitude of myocardial infarction. To clarify the question, if the above-mentioned markers are influenced by sex or ischemic preconditioning, experiments on isolated rat hearts using the Langendorff technique were performed. Using the hearts of 12 male and 12 female Wistar rats a local ischemia was induced through ligation of the left coronary artery. Furthermore, 12 male rat hearts underwent ischemic preconditioning of the heart by stopping the perfusion of the whole heart for 30 min and subsequently reperfusing the heart for another 60 min, before inducing local ischemia. The perfusion time after ligation varied from 10 to 60 min. A control group was comprised out of 6 male and 2 female rat hearts. These were placed in the Langendorff system for 60 min without further manipulation or received ischemic preconditioning without subsequent local ischemia or were excised without being mounted on the Langendorff system at all. All hearts were fixed in formalin and stained immunohistochemically. Depletion of the marker cTnT appeared to be less in females when compared to male hearts, for all other markers tested, no apparent difference in staining results were seen when comparing male and female rat hearts. Male rat hearts with ischemic preconditioning showed no difference compared to male rat hearts without ischemic preconditioning when stained fort dityrosine. Connexin 43 staining was less pronounced in hearts with ischemic preconditioning, whereas cTnI as well as cTnT depletion was more pronounced in preconditioned hearts. The presented findings indicate to some extent the vulnerability of the investigated markers for the influencing factors tested.

Keywords

Myocardial infarction Sex Ischemic preconditioning Immunohistochemistry Animal model 

Notes

Compliance with ethical standards

The experiments in this study were conducted in accordance with the German legislation on protection of animals and the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996). The protocol for the Langendorff experiments was approved by the local Animal Ethics Committee (Project No. O 27/11).

References

  1. 1.
    Mayer F, Propper S, Ritz-Timme S (2014) Dityrosine, a protein product of oxidative stress, as a possible marker of acute myocardial infarctions. Int J Legal Med 128(5):787–794CrossRefGoogle Scholar
  2. 2.
    Mayer F, Falk M, Huhn R, Behmenburg F, Ritz-Timme S (2016) Dityrosine as a marker of acute myocardial infarction? Experiments with the isolated Langendorff heart. Int J Legal Med 130:1053–1060CrossRefGoogle Scholar
  3. 3.
    Campobasso CP, Dell’Erba AS, Addante A, Zotti F, Marzullo A, Colonna MF (2008) Sudden cardiac death and myocardial iaschemia indicators: a comparative study of four immunohistochemical markers. Am J Forensic Med Pathol 29:154–161CrossRefGoogle Scholar
  4. 4.
    Sabatasso S, Mangin P, Fracasso T, Moretti M, Docquier M, Djonov V (2016) Early markers for myocardial ischemia and sudden cardiac death. Int J Legal Med 130:1265–1280CrossRefGoogle Scholar
  5. 5.
    Isles CG, Hole DJ, Hawthorne VM, Lever AF (1992) Relation between coronary risk and coronary mortality in women of the Renfrew and Paisley survey- comparison with men. Lancet 339:702–706CrossRefGoogle Scholar
  6. 6.
    Guerra S, Leri A, Wang X, Finato N, Di Loreto C, Beltrami CA et al (1999) Myocyte death in the failing human heart is gender dependent. Circ Res 85(9):856–866CrossRefGoogle Scholar
  7. 7.
    Wang F, He Q, Sun Y, Dai X, Yang XP (2010) Female adult mouse cardiomyocytes are protected against oxidative stress. Hypertension 55(5):1172–1178CrossRefGoogle Scholar
  8. 8.
    Bae S, Zhang L (2005) Gender differences in cardioprotection against ischemia/reperfusion injury in adult rat hearts: focus on Akt and protein kinase C signaling. J Pharmacol Exp Ther 315(3):1125–1135CrossRefGoogle Scholar
  9. 9.
    Reiter R, Henry TD, Traverse JH (2013) Preinfarction angina reduces infarct size in ST-elevation myocardial infarction treated with percutaneous coronary intervention. Circ Cardiovasc Interv 6(1):52–58CrossRefGoogle Scholar
  10. 10.
    Iwasaka T, Nakamura S, Karakawa M, Sugiura T, Inada M (1994) Cardioprotective effect of unstable angina prior to acute anterior myocardial infarction. Chest 105(1):57–61CrossRefGoogle Scholar
  11. 11.
    Ovize M, Kloner RA, Hale SL, Przyklenk K (1992) Coronary cyclic flow variations "precondition" ischemic myocardium. Circulation 85(2):779–789CrossRefGoogle Scholar
  12. 12.
    Liu YG, Downey JM (1992) Ischemic preconditioning protects against infarction in rat-heart. Am J Physiol 263(4):H1107–H1111Google Scholar
  13. 13.
    Schott RJ, Rohmann S, Braun ER, Schaper W (1990) Ischemic preconditioning reduces infarct size in swine myocardium. Circ Res 66(4):1133–1142CrossRefGoogle Scholar
  14. 14.
    Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74(5):1124–1136CrossRefGoogle Scholar
  15. 15.
    Jenkins DP, Pugsley WB, Yellon DM (1995) Ischaemic preconditioning in a model of global ischaemia: infarct size limitation, but no reduction of stunning. J Mol Cell Cardiol 27(8):1623–1632CrossRefGoogle Scholar
  16. 16.
    Efstathiou A, Seraskeris S, Papakonstantinou C, Aidonopoulos A, Lazou A (2001) Differential effect of preconditioning on post-ischaemic myocardial performance in the absence of substantial infarction and in extensively infarcted rat hearts. Eur J Cardiothorac Surg 19:493–499CrossRefGoogle Scholar
  17. 17.
    Korthuis RJ, Gute DC, Cepinska G, Kvietsy PR (1998) Cellular mechanisms of acute versus delayed preconditioning. Pathophysiology 5:35–48CrossRefGoogle Scholar
  18. 18.
    Carden DL, Granger DN (2000) Pathophysiology of ischaemia-reperfusion injurry. J Pathol 200 190:255–266CrossRefGoogle Scholar
  19. 19.
    Bell RM, Mocanu MM, Yellon DM (2011) Retrograde heart perfusion: the Langendorff technique of isolated heart perfusion. J Mol Cell Cardiol 50:940–950CrossRefGoogle Scholar
  20. 20.
    Li GC, Vasquez JA, Gallagher KP, Lucchesi BR (1990) Myocardial protection with preconditioning. Circulation 82:609–619CrossRefGoogle Scholar
  21. 21.
    Murry CE, Richard VJ, Jennings RB, Reimer KA (1991) Myocardial protection is lost before contractile funtion recovers from ischemic preconditioning. Am J Physiol 260(29):H796–H804Google Scholar
  22. 22.
    Miura T, Noto T, Adachi T, Endoh A, Goto M, Urabe K, Iimura O (1991) Does myocardial stunning contribute to infarct limitation by preconditioning? Circulation 84(6):2504–2512CrossRefGoogle Scholar
  23. 23.
    Giulivi C, Traaseth NJ, Davies KJ (2003) Tyrosine oxidation products: analysis and biological relevance. Amino Acids 25(3–4):227–232CrossRefGoogle Scholar
  24. 24.
    Beardslee MA, Lerner DL, Tadros PN, Laing JG, Beyer EC, Yamada KA, Kléber ÁG, Schuessler RB, Saffitz JE (2000) Dephosphorylation and intracellular redistribution of ventricular connexin43 during electrical uncoupling induced by Ischaemia. Circ Res 87:656–662CrossRefGoogle Scholar
  25. 25.
    Brandenburger T, Huhn R, Galas A, Pannen BH, Keitel V, Barthel F, Bauer I, Heinen A (2014) Remote ischemic preconditioning preserves connexin 43 phosphorylation in the rat heart in vivo. J Transl Med 12(28):228CrossRefGoogle Scholar
  26. 26.
    Ortmann C, Pfeiffer H, Brinkmann B (2000) A comparative study on the immunohistochemical detection of early myocardial damage. Int J Legal Med 113:215–220CrossRefGoogle Scholar
  27. 27.
    Osuna E, Pèrez-Cárceles MD, Alvarez MV, Noguera J, Luna A (1998) Cardiac troponin I (cTn I) and the postmortem diagnosis of myocardial infarction. Int J Legal Med 111:173–176CrossRefGoogle Scholar
  28. 28.
    Kobayashi C, Miura M, Miyaishi S (2017) Postmortem exudation of myoglobin from striated muscle during formalin fixation (abstract). Rechtsmedizin 27:311–404CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute for Legal MedicineUniversity Hospital DüsseldorfDüsseldorfGermany
  2. 2.Hospital EmmentalLangnau i.E.Switzerland
  3. 3.Department of AnaesthesiologyUniversity Hospital DüsseldorfDüsseldorfGermany

Personalised recommendations