Free radical biology & medicine
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Free Radic. Biol. Med. · Mar 2009
Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production.
Mechanical ventilation (MV) is a life-saving intervention used in patients with acute respiratory failure. Unfortunately, prolonged MV results in diaphragmatic weakness, which is an important contributor to the failure to wean patients from MV. Our laboratory has previously shown that reactive oxygen species (ROS) play a critical role in mediating diaphragmatic weakness after MV. ⋯ Prolonged MV was also associated with diaphragmatic mitochondrial oxidative damage as indicated by increased lipid peroxidation and protein oxidation. Finally, our data also reveal that the activities of the electron transport chain complexes II, III, and IV are depressed in mitochondria isolated from diaphragms of MV animals. In conclusion, these results are consistent with the concept that diaphragmatic inactivity promotes an increase in mitochondrial ROS emission, mitochondrial oxidative damage, and mitochondrial respiratory dysfunction.
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Free Radic. Biol. Med. · Mar 2009
Hypothermic preconditioning of endothelial cells attenuates cold-induced injury by a ferritin-dependent process.
Hypothermia for myocardial protection or storage of vascular grafts may damage the endothelium and impair vascular function upon reperfusion/rewarming. Catalytic iron pools and oxidative stress are important mediators of cold-induced endothelial injury. Because endothelial cells are highly adaptive, we hypothesized that hypothermic preconditioning (HPC) protects cells at 0 degrees C by a heme oxygenase-1 (HO-1) and ferritin-dependent mechanism. ⋯ HO-1 was not induced. When HPC-mediated increases in ferritin were blocked by deferoxamine, protection at 0 degrees C was diminished. We conclude that HPC-mediated endothelial protection from hypothermic injury is an iron- and ferritin-dependent process.