P Eyenga1,2, D Roussel3, B Rey4, P Ndille5, L Teulier3, F Eyenga6, C Romestaing3, J Morel7, V Gueguen-Chaignon8, S-S Sheu9. 1. Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, 19107, USA. eyenga38@yahoo.fr. 2. Université Claude Bernard Lyon 1, 69008, Lyon, France. eyenga38@yahoo.fr. 3. Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés, UMR 5023, Université de Lyon, Université Lyon1, CNRS, 69622, Villeurbanne, France. 4. Laboratoire de Biométrie et Biologie Evolutive, UMR 5558, Université de Lyon, Université Lyon1, CNRS, 69622, Villeurbanne, France. 5. Département de Chirurgie, Centre Hospitalier D'Ebomé, Kribi, Cameroun. 6. Université Claude Bernard Lyon 1, 69008, Lyon, France. 7. Service de réanimation chirurgicale, CHU de Saint Etienne, 42000, Saint Etienne, France. 8. Protein Science Facility, ENS de Lyon, Inserm, US8, SFR Biosciences UMS 3444 - CNRS Université Claude Bernard Lyon 1, 69007, Lyon, France. 9. Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Abstract
BACKGROUND: To 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. METHODS: A 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. RESULTS: CLP 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. CONCLUSION: In an experimental model of sepsis, early initiation of mechanical ventilation restores diaphragm mitochondrial function.
BACKGROUND: To 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. METHODS: A 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. RESULTS:CLPrats showed severe hypotension, metabolic acidosis, and upregulation of diaphragm IL-1β mRNA expression. Compared to sham controls, spontaneously breathing CLPrats 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 CLPrats; lowered mitochondrial ROS production by the complex 3; and preserved cytochrome c oxidase activity. CONCLUSION: In an experimental model of sepsis, early initiation of mechanical ventilation restores diaphragm mitochondrial function.
Authors: Marloes van den Berg; Pleuni E Hooijman; Albertus Beishuizen; Monique C de Waard; Marinus A Paul; Koen J Hartemink; Hieronymus W H van Hees; Michael W Lawlor; Lorenza Brocca; Roberto Bottinelli; Maria A Pellegrino; Ger J M Stienen; Leo M A Heunks; Rob C I Wüst; Coen A C Ottenheijm Journal: Am J Respir Crit Care Med Date: 2017-12-15 Impact factor: 21.405
Authors: N Fujimura; S Sumita; M Aimono; Y Masuda; Y Shichinohe; E Narimatsu; A Namiki Journal: Am J Respir Crit Care Med Date: 2000-12 Impact factor: 21.405
Authors: G Hilbert; D Gruson; F Vargas; R Valentino; G Gbikpi-Benissan; M Dupon; J Reiffers; J P Cardinaud Journal: N Engl J Med Date: 2001-02-15 Impact factor: 91.245