Heart failure and high mortality rates are associated with severe sepsis. Recently, focus has been on mitochondrial ultrastructural changes and function due to sepsis and sepsis-related pathologies. Chopra et al. (2011) has provided data showing the involvement of the mitochondrial-mediated intrinsic apoptosis cascade in regulating adult rat ventricular myocyte (ARVM) dysfunction in sepsis. Experimental endotoxemia has shown mitochondrial membrane potential collapse, membrane permeability changes and release of cytochrome C to be indicators of mitochondrial dysfunction. Outer mitochondrial membrane (OMM) permeability is controlled by Bax translocation, resulting Voltage Dependent Anion Channels (VDACs) pores in the OMM and activation of mitoKATP channels in the inner mitochondrial membrane. Endotoxins can induce mitochondrial damage and there is a correlation between the severity of sepsis and mitochondrial damage and dysfunction. Since the progression of sepsis occurs from vascular dysfunction to organ dysfunction, in the current study we examined mitochondrial dysfunction in endotoxic HUVEC cells. This study has provided evidence for 5HD, a putative mitoKATP blocker, in the preservation of ΔΨm in endotoxic HUVEC. Additionally, 5HD appears to prevent Apaf-1 expression and reduce H2O2 generation in endotoxic HUVEC
