RT Journal Article
SR Electronic
T1 03 Cancer therapy drug, doxorubicin, exacerbates myocardial ischaemia reperfusion injury
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP e1
OP e1
DO 10.1136/hrt.2010.213496.3
VO 97
IS 1
A1 A M Gharanei
A1 A Hussain
A1 H L Maddock
YR 2011
UL http://heart.bmj.com/content/97/1/e1.3.abstract
AB Drug-induced cardiotoxicity is a major concern to the pharmacological industry and it is one of the main reasons for non-approval, re-labelling, warnings and withdrawal of pharmaceutical compounds from the market.1 Doxorubicin is an anthracycline antibiotic used in cancer therapy. Although issues relating to Doxorubicin and cardiac safety have been well established in normal conditions, the effects of this drug on the myocardium during ischaemia-reperfusion have not been investigated in detail to date. Studies were undertaken in Langendorff hearts and adult/neonatal ventricular myocytes subjected to ischaemia-reperfusion. Hearts underwent triphenyl tetrazolium staining for infarct size assessment. Treatment groups (n=7–10) were perfused in the presence or absence of Doxorubicin. Following isolation, neonatal or adult cardiomyocytes were subjected to simulated ischaemia-reoxygenation and Doxorubicin was administered at reoxygenation. Cellular injury was subsequently determined by measurement of live/death ratio and apoptosis using flow cytometry. Administration of Doxorubicin in normoxic conditions or during ischaemia-reperfusion significantly increased infarct size to risk ratio (%) compared to respective non-treated controls (30±5% and 81±6% Doxorubicin vs 10±2% and 65±3% non-treated control, respectively, p<0.01). Doxorubicin also significantly increased apoptosis and decreased cell viability after reoxygenation compared to control. This is the first study to show that the anticancer drug Doxorubicin exacerbates myocardial ischaemia reperfusion injury. Further studies are being undertaken to determine the cellular mechanism via which Doxorubicin mediates increased myocardial injury in conditions of ischaemia-reperfusion.