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European Heart Journal Advance Access originally published online on October 3, 2006
European Heart Journal 2006 27(21):2611; doi:10.1093/eurheartj/ehl294
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© The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Iloprost attenuates doxorubicin-induced cardiac injury in a murine model without compromising tumor suppression: reply

Tomas G. Neilan

Division of Cardiology
Department of Medicine
Massachusetts General Hospital
Boston MA
USA
Tel: +1 617 7241991
Fax: +1 617 7268383
E-mail address: tneilan{at}partners.org

Desmond J. Fitzgerald

University College Dublin
Belfield
Dublin 4
Ireland

We would like to thank Drs Kuramochi, Takagi, and Morita for their interest in our work. Although measurement of apoptosis using the TUNEL assay is validated and extensively published in this model,1,2 we agree that, likely due to the transient nature of the process, a significant proportion of apoptotic nuclei will not be detected and, either due to sample harvesting, preparation, and staining protocols, a percentage of false positive results will be reported. The second point raised is also of considerable interest, as, although TUNEL-positive cells have been detected as early as 24 h after administration of doxorubicin in animal models,3 discordance has been suggested in the extent of the ventricular dysfunction and the degree of apoptosis. This discordance may be explained by the effect of doxorubicin on large myofilament proteins such as titin.4 Finally, we agree that further work, such as that suggested, is required to differentiate whether the protective effects of iloprost are mediated via prostacyclin or nuclear hormone receptors.

References

  1. Khaw BA, Silva JD, Petrov A, Hartner W. (2002) Indium 111 antimyosin and Tc-99 m glucaric acid for noninvasive identification of oncotic and apoptotic myocardial necrosis. J Nucl Cardiol 9:471–481.[CrossRef][Web of Science][Medline]
  2. Kotamraju S, Konorev EA, Joseph J, Kalyanaraman B. (2000) Doxorubicin-induced apoptosis in endothelial cells and cardiomyocytes is ameliorated by nitrone spin traps and ebselen. Role of reactive oxygen and nitrogen species. J Biol Chem 275:33585–33592.[Abstract/Free Full Text]
  3. Neilan TG, Jassal DS, Perez-Sanz TM, Raher MJ, Pradhan AD, Buys ES, Ichinose F, Bayne DB, Halpern EF, Weyman AE, Derumeaux G, Bloch KD, Picard MH, Scherrer-Crosbie M. (2006) Tissue Doppler imaging predicts left ventricular dysfunction and mortality in a murine model of cardiac injury. Eur Heart J 27:1868–1875.[Abstract/Free Full Text]
  4. Lim CC, Zuppinger C, Guo X, Kuster GM, Helmes M, Eppenberger HM, Suter TM, Liao R, Sawyer DB. (2004) Anthracyclines induce calpain-dependent titin proteolysis and necrosis in cardiomyocytes. J Biol Chem 279:8290–8299.[Abstract/Free Full Text]

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This Article
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