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Background: Ischemia-reperfusion injury (IRI) is a major challenge in liver transplantation. The mitochondrial pathway plays a pivotal role in hepatic IRI. Levosimendan, a calcium channel sensitizer, was shown to attenuate apoptosis after IRI in animal livers. The aim of this study was to investigate the effect of levosimendan on apoptosis in human hepatocytes.
Methods: Primary human hepatocytes were either exposed to hypoxia or cultured under normoxic conditions. After the hypoxic phase, reoxygenation was implemented and cells were treated with different concentrations of levosimendan (10ng/ml, 100ng/ml, 1000ng/ml). The overall metabolic activity of the cells was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and aspartate aminotransferase (AST) levels were determined in order to quantify hepatic injury. Fluorescence-activated cell sorting (FACS) analysis was applied to measure necrosis and apoptosis. Finally, Western blotting was performed to analyze apoptotic pathway proteins.
Results: Administration of levosimendan during reperfusion increases the metabolic activity of human hepatocytes and decreases AST levels. Moreover, apoptosis after IRI is reduced in treated vs. untreated hepatocytes, and levosimendan prevents down-regulation of the anti-apoptotic protein Bcl-2 as well as up-regulation of the pro-apoptotic protein BAX.
Conclusion: The present study suggests a protective effect of levosimendan on human hepatocytes. Our findings suggest that treatment with levosimendan during reperfusion attenuates apoptosis of human hepatocytes by influencing BAX and Bcl-2 levels.
Patients who undergo endovascular repair of aortic aneurysms (EVAR) require life-long surveillance because complications including, in particular, endoleaks, aneurysm rupture, and graft dislocation are diagnosed in a certain share of the patient population and may occur at any time after the original procedure. Radiation exposure in patients undergoing EVAR and post-EVAR surveillance has been investigated by previous authors. Arriving at realistic exposure data is essential because radiation doses resulting from CT were shown to be not irrelevant. Efforts directed at identification of factors impacting the level of radiation exposure in both the course of the EVAR procedure and post-EVAR endovascular interventions and CTAs are warranted as potentially modifiable factors may offer opportunities to reduce the radiation. In the light of the risks found to be associated with radiation exposure and considering the findings above, those involved in EVAR and post-EVAR surveillance should aim at optimal dose management.