There are also important differences between species, and more im

There are also important differences between species, and more import antly, between animals and humans. Fourth, some in vivo animal experiments used re peated administrations of 5 FU, but numerous studies have used regimens in which animals were treated with only a single and or a very high 5 FU dose. In clinical practice, 5 FU is often administered according to the De Gramont schedule where a short bolus infusion is given followed by a 48 hour continuous Inhibitors,Modulators,Libraries infusion. Hence, dif ferences in administration schedules and doses may also limit the extrapolation of the results from these studies to clinical settings. Fifth, most of the findings in the human studies were not confined to patients experiencing cardiotoxicity, as only NT proBNP and endothelin 1 were higher in pa tients with cardiotoxicity.

Hence, for nearly all findings, their role in the pathogenesis of cardiotoxicity is still unclear. Finally, some types of studies that can be conducted in animals are difficult to carry out in human patients. For example, biopsy samples are hard to obtain and carry a risk of bleeding and myocardial Inhibitors,Modulators,Libraries wall perforation for the patient. Such risks may outweigh the expected benefit Inhibitors,Modulators,Libraries for the patient, and therefore make such procedures un reasonable to perform. Conclusions This review indicates that there is no evidence for a single mechanism responsible for 5 FU induced cardiotoxicity, and the underlying mechanisms might be multifactorial. The proposed cardiotoxic pathways leading to myocardial and endothelial Inhibitors,Modulators,Libraries damage are not mutually exclusive, and they may each contribute to cardiovascular dysfunction resulting in the clinical picture of cardiotoxicity.

Further research is needed to elucidate the pathogenesis of this side effect. Studies on cardiac and endothelial cell lines might contribute to further elucidation of the cellular re sponse to 5 FU. A human study with continuous ECG monitoring concurrent with measurements of the brachial artery diameters could be interesting, to explore the theory of arterial vasospasm leading Inhibitors,Modulators,Libraries to myocardial ischemia. Other methods to further study the pathogenesis of 5 FU induced cardiotoxicity could be studies of myocardial perfusion with magnetic resonance scanning or PET rubid ium scanning of the heart in patients presenting with signs of cardiotoxicity.

Background Physiological or pathological processes that disturb pro tein folding in the endoplasmic reticulum cause ER stress and activate a set of signalling pathways termed the Unfolded Protein Response. In the ischemic state the lack of oxygen and nutrients to the heart can cause lasting damage to this vital organ through cardio myoblasts death. Ischemic conditions are known to affect ER homeostasis in ways predicted to activate the UPR. Activation of UPR signalling due to ER stress is associated with the development of ischemic heart disease.

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