In contrast, significant depletion of Gemcitabine order pO2, increase in deoxy hemoglobin levels, in crease in 2,3 BPG levels and decrease in ATP levels were only observed for erythrocytes treated with 5 FU alone and erythrocytes treated with the combination of 5 FU and cisplatin. Hence, altered RBC metabolism might be a cause of 5 FU induced ischemia. However, it is unknown whether the changes in RBC metabolism and morphology observed in vitro also occur in vivo. Also, the link between these changes and clinical signs of cardiotoxicity in pa tients is not proven. It is unlikely that changes in blood viscosity are a part of the pathogenesis of 5 FU induced cardiotoxicity, as studies on blood viscosity reported con flicting results. Other proposed mechanisms for 5 FU induced cardiotoxicity Few other mechanisms for 5 FU induced cardiotoxicity have been proposed.

Lemaire et al. proposed that 5 FU cardiotoxicity was Inhibitors,Modulators,Libraries due to degradation products formed in the basic medium in which 5 FU is dissolved. The compound thought to be responsible for the cardi otoxicity is fluoroacetate, which is formed through alka line hydrolysis of 5 FU and by catabolism of 5 FU in the liver. However, the consistent nature of 5 FU and capecitabine induced cardiotoxicity, regardless of the solutions or formulations used, makes it unlikely that 5 FU cardiotoxicity is Inhibitors,Modulators,Libraries due to degradation products formed in the solution of 5 FU in a basic medium. Thus, if fluoroacetate plays Inhibitors,Modulators,Libraries a role in 5 FU induced car diotoxicity it is likely because of metabolism of 5 FU to fluoroacetate in the liver.

Toxic myocarditis has been proposed by Sasson et al, as they found biventricular dilation and diffusely scattered areas of cell necrosis associated with an inflam matory infiltrate, on autopsy of a case of 5 FU induced fatal cardiogenic shock. Limitations First, the selection of studies concerning the pathophysi ology of 5 Inhibitors,Modulators,Libraries FU cardiotoxicity could not be based on objective criteria, Inhibitors,Modulators,Libraries but instead relied on the authors judg ments of which studies were concerned with the patho physiology of 5 FU induced cardiotoxicity. Still, we made a broad inclusion of studies that investigated the effects of 5 FU on any part of the cardiovascular system. There fore, we believe that this review makes up a comprehen sive and systematic synthesis of the results from the pathophysiological studies of 5 FU cardiotoxicity. How ever, Belinostat HDAC as our literature search was restricted to English, a few studies may have been missed. Second, most experimental studies included few ani mals and were only carried out once. Hence the statis tical powers in these studies were low and the findings rarely confirmed in other studies, which makes those findings less consistent.