To inhibit cell death in models of ceramide-induced toxicity and myocardial ischaemia and reperfusion injury. Furthermore, it was recently shown that treatment with mdivi-1 protected against pressure induced heart failure by ameliorating left ventricular dysfunction and promoting angiogenesis. Increase in apoptosis and abnormal mitophagy noticed in pressure overload samples were also prevented when treated with mdivi-1. Cancers are likely to develop in the later stages of life, when the chances of developing heart diseases are equally high. Patients with pre-existing heart diseases are usually excluded or underrepresented in clinical trials, which aim to identify the efficacy and potential adverse effects of drugs. We have recently shown that doxorubicin administration at reperfusion exacerbates ischaemia reperfusion injury, which was prevented when co-administered with cyclosporin A. It is therefore necessary to investigate the off-target effects of anti-cancer therapeutics or adjunct therapies in stressed or diseased conditions such as ischaemia and reperfusion injury. Given that doxorubicin-induced cardiotoxicity may be mediated by an imbalance in mitochondrial fusion and fission, we investigated the effects mdivi-1 on doxorubicin-induced cardiotoxicity using the Langendorff model in na?ve and in conditions of ischaemia and reperfusion injury. A model of oxidative stress was used to record the time taken to depolarisation and hypercontracture of cardiac myocytes upon drug treatment and western blot analysis was used to PF-4217903 evaluate the levels signalling proteins. Data on the effects of mdivi-1 on the cytotoxicity of doxorubicin was also assessed in HL60 cell line. Doxorubicin treatment is known to cause cardiovascular toxicity due to the generation of reactive oxygen species and calcium overload. Previous research has demonstrated that doxorubicin induced toxicity affects mitochondrial bioenergetics and causes mitochondrial fragmentation. We demonstrate that doxorubicin induced dysfunction on the haemodynamic parameters of the hearts are reversed by mdivi-1, a relatively specific inhibitor of mitochondrial division. Doxorubicin induced effects of cardiac function has been reported in in vivo and in vitro studies. Doxorubicin has previously been found to reduce both left ventricular developed pressure and heart rate, also shown in this study. Interestingly, the presented data show that doxorubicin treatment in the na?ve hearts caused a drop in the heart rate readings as opposed to its effects in conditions of ischaemia and reperfusion injury where no significant decrease in the heart rate values were recorded. One possible explanation for this effect could be the level of oxygen, previously published work has indicated that doxorubicin-induced decrease in the heart rate was more prominent when the heart were perfused with 95% oxygen as compared to 20% oxygen. We also show that co-treatment with mdivi-1 abrogated the detrimental effects of doxorubicin on left ventricular developed pressure. Interestingly, treatment with mdivi-1 was shown to ameliorate left ventricular dysfunction caused by pressure overload heart failure as assessed by left ventricular chamber diameter and fractional shortening. Mitochondrial fragmentation is proposed to be a major player in exacerbation of heart failure, inhibition of fragmentation is therefore thought to confer cardioprotection. Recent research has indicated that mitochondrial dynamics play a crucial role in cell physiology and growing evidence suggests that a balance between mitochondrial fission and fusion plays a vital role in pathological conditions. Studies have also shown that mitochondrial oxidative stress, which is also induced by doxorubicin treatment, leads to fragmentation of the mitochondria, which were attenuated with reactive oxygen species scavengers. Mitochondrial fragmentation has been found to mediate cellular function and apoptosis. Mdivi-1 has been suggested to have therapeutic potential for a variety of diseases such as stroke, myocardial GSI-IX side effects infarction and neurodegenerative disorders. In the current study, flow cytometric analyses of p-Drp1 levels show a significant up regulation of p-Drp1 levels following treatment with doxorubicin, which was prevented when doxorubicin was co-administered with mdivi-1. Elevated levels of mitochondrial fission proteins have been reported in response to ceramide and doxorubicin induced toxicity. It has been demonstrated that mdivi-1 inhibits GTPase activity by blocking self-assembly of Drp1.