Abstract
BackgroundTo describe the effect of mechanical ventilation on diaphragm mitochondrial oxygen consumption, ATP production, reactive oxygen species (ROS) generation, and cytochrome c oxidase activity and content, and their relationship to diaphragm strength in an experimental model of sepsis.MethodsA cecal ligation and puncture (CLP) protocol was performed in 12 rats while 12 controls underwent sham operation. Half of the rats in each group were paralyzed and mechanically ventilated. We performed blood gas analysis and lactic acid assays 6 h after surgery. Afterwards, we measured diaphragm strength and mitochondrial oxygen consumption, ATP and ROS generation, and cytochrome c oxidase activity. We also measured malondialdehyde (MDA) content as an index of lipid peroxidation, and mRNA expression of the proinflammatory interleukin-1β (IL-1β) in diaphragms.ResultsCLP rats showed severe hypotension, metabolic acidosis, and upregulation of diaphragm IL-1β mRNA expression. Compared to sham controls, spontaneously breathing CLP rats showed lower diaphragm force and increased susceptibility to fatigue, along with depressed mitochondrial oxygen consumption and ATP production and cytochrome c oxidase activity. These rats also showed increased mitochondrial ROS generation and MDA content. Mechanical ventilation markedly restored mitochondrial oxygen consumption and ATP production in CLP rats; lowered mitochondrial ROS production by the complex 3; and preserved cytochrome c oxidase activity.ConclusionIn an experimental model of sepsis, early initiation of mechanical ventilation restores diaphragm mitochondrial function.
Highlights
To describe the effect of mechanical ventilation on diaphragm mito‐ chondrial oxygen consumption, adenosine triphosphate (ATP) production, reactive oxygen species (ROS) generation, and cytochrome c oxidase activity and content, and their relationship to diaphragm strength in an experimental model of sepsis
If mitochondria dysfunction was not involved in diaphragm weakness, the ROS generated during sepsis [12] and mechanical ventilation (MV) [13] would not be decreased by anti-oxidant infusion [12, 14]
The present study aimed to investigate the effects of MV on diaphragm mitochondrial function during sepsis in rats subjected to cecal ligation and puncture (CLP)
Summary
To describe the effect of mechanical ventilation on diaphragm mito‐ chondrial oxygen consumption, ATP production, reactive oxygen species (ROS) generation, and cytochrome c oxidase activity and content, and their relationship to diaphragm strength in an experimental model of sepsis. A previous experimental study has shown transient beneficial effect of MV on diaphragm function [8], which may be absent in the short term [9] and prolonged MV [10] in the endotoxemia model of sepsis. It is still unclear if ROS generated by the mitochondrial electron transport chain alteration are involved in diaphragm failure related to sepsis and MV. A recent clinical study has shown that mitochondrial function is unaffected by prolonged MV [11], while an animal model of sepsis and short-term MV has shown the opposite result [9]. If mitochondria dysfunction was not involved in diaphragm weakness, the ROS generated during sepsis [12] and MV [13] would not be decreased by anti-oxidant infusion [12, 14]
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