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European Heart Journal Advance Access originally published online on April 19, 2006
European Heart Journal 2006 27(10):1251-1256; doi:10.1093/eurheartj/ehl003
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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 tumour suppression

Tomas G. Neilan1,*, Davinder S. Jassal2, Michael F. Scully1, Gang Chen4, Catherine Deflandre6, Hester McAllister6, Elaine Kay5, Sandra C. Austin1, Elkan F. Halpern3, Judy H. Harmey4 and Desmond J. Fitzgerald1

1 Department of Clinical Pharmacology, Institute of Biopharmaceutical Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
2 Cardiac Ultrasound Laboratory, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, USA
3 The Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA, USA
4 Department of Surgery, Beaumont Hospital, Dublin, Ireland
5 Department of Pathology, Beaumont Hospital, Dublin, Ireland
6 Department of Veterinary Medicine, University College Dublin, Ireland

Received 21 July 2004; revised 15 March 2006; accepted 6 April 2006; online publish-ahead-of-print 19 April 2006.

* Corresponding author. Tel: +1 617 7241991; Fax: +001 617 7268383. E-mail address: tneilan{at}partners.org

See page 1137 for the editorial comment on this article (doi:10.1093/eurheartj/ehi702)

Aims The use of doxorubicin (DOX) as a chemotherapeutic agent is limited by cardiac injury. Iloprost, a stable synthetic analogue of prostacyclin, has previously been shown to protect against DOX-induced cardiomyocyte injury in vitro. Here, we addressed whether iloprost is cardioprotective in vivo and whether it compromises the anti-tumour efficacy of DOX.

Methods and results Lewis Lung Carcinoma cells were implanted subcutaneously in the flank of C57BL/6 mice. DOX treatment was commenced from when tumours became visible. Iloprost was administered from prior to DOX treatment until sacrifice. Echocardiography and invasive haemodynamic measurements were performed immediately before sacrifice. As expected, DOX induced cardiac cell apoptosis and cardiac dysfunction, both of which were attenuated by iloprost. Also, iloprost alone had no effect on tumor growth and indeed, did not alter the DOX-induced suppression of this growth.

Conclusion In a murine model, iloprost attenuated the acute cardiac injury and dysfunction induced by DOX therapy without compromising its chemotherapeutic effect.

Key Words: Doxorubicin • Cardiotoxicity • Cyclooxygenase • Prostaglandins


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