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• W2000478464 abstract "Bacterial toxins cause cardiac dysfunction and death through an inflammatory process, but the mechanism remains unclear. Simvastatin is recognized as having anti-inflammatory properties beyond its lipid-lowering effects. We examined Staphylococcus aureus α-toxin in isolated heart and in vivo models and tested simvastatin's effects in sepsis. Isolated Langendorff-perfused rat hearts were exposed to a recirculating perfusate containing α-toxin (0.5 µg mL−1). Compared with controls, there was a significant increase in coronary perfusion pressure and fall in myocardial performance. Significant increases in p53 expression and apoptosis (1.3 ± 0.5 to 7.1 ± 1.4 terminal deoxynucleotidyl transferase nick end labeling-positive cells; P < 0.05) compared with controls were observed, but markers of necrosis were similar. In parallel experiments, anaesthetized rats receiving α-toxin (40 µg kg−1, i.v.) had in vivo hemodynamic parameters and serum markers of necrosis monitored for 4 h before the hearts were analyzed for histological change, p53 expression, and apoptosis. Over 4 h, α-toxin exposure produced substantial hemodynamic effects. In addition, p53 expression (0.2 ± 0.2 to 7.1 ± 0.5 p53-positive myocytes; P < 0.05), TNF-α levels, the degree of apoptosis, and markers of necrosis were all significantly increased compared with control animals. Pretreatment with simvastatin protected against α-toxin-induced sepsis associated with reduced p53, TNF-α, apoptosis, and necrosis. We found significant changes in systemic hemodynamics, coronary perfusion pressure, myocardial function, and increased p53 expression with apoptosis due to bacterial exotoxin. In vivo changes were significantly inhibited by pretreatment with simvastatin. We provide novel evidence for the mechanisms by which septicemia causes myocardial depression and hint at a potential role for simvastatin as an inhibitor of apoptosis in sepsis." @default.
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• W2000478464 date "2008-04-01" @default.
• W2000478464 modified "2023-10-06" @default.
• W2000478464 title "APOPTOSIS CONTRIBUTES TO SEPTIC CARDIOMYOPATHY AND IS IMPROVED BY SIMVASTATIN THERAPY" @default.
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• W2000478464 doi "https://doi.org/10.1097/shk.0b013e318142c434" @default.
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