Matallo 2013 Abstract MiP2013

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Matallo J, Gröger M, Wagner K, Wagner F, Radermacher P, Calzia E (2013) Effects of mechanical ventilation after blunt chest trauma on diaphragmatic mitochondrial respiration in chronically cigarette smoke exposed mice: A clinically relevant model? Mitochondr Physiol Network 18.08.
Link:
Jose Matallo
MiP2013, Book of Abstracts Open Access

Matallo J, Gröger M, Wagner K, Wagner F, Radermacher P, Calzia E (2013)

Event: MiPNet18.08_MiP2013

Previous studies clearly indicate that diaphragm disuse during mechanical ventilation (MV) rapidly leads to atrophy of this muscle [1]. On the biochemical level, this MV related diaphragmatic weakness is due to an increased production of reactive oxygen species (ROS) and impaired mitochondrial respiration [2,3]. The dysfunction of the diaphragm is a major cause of difficult weaning from MV. This issue is a leading problem in critical care medicine, and a particularly severe challenge in patients with pre-existing pulmonary disorders like chronic obstructive pulmonary disease (COPD). However, no data are available yet on the effects of MV on diaphragmatic function especially in subjects with pulmonary conditions resembling human COPD. Therefore, our aim was to measure mitochondrial respiratory activity in diaphragm and heart in chronically cigarette smoke exposed (CSE) mice, i.e. in a COPD-model, after a standardized blunt chest trauma [4] and 5 hours of mechanical ventilation.

Maximum mitochondrial respiration in small, homogenized biopsies of heart and diaphragm was measured in the FCCP-induced uncoupled state under combined stimulation of the respiratory system with Complex I (pyruvate, malate and glutamate) and Complex II (succinate) substrates using an Oxygraph-2k (Oroboros Instruments, Austria). We studied 4 groups of animals (controls vs. CSE with or without trauma and MV, N = 5-8).

Only in the diaphragm of CSE mice mitochondrial respiration already decreased after the short period of MV (Figure 1).

In contrast to healthy individuals, in subjects suffering from chronic pulmonary diseases and airway obstruction similar to human COPD diaphragmatic mitochondrial dysfunction already results from short periods of MV and inactivity of the respiratory muscles.


O2k-Network Lab: DE Ulm Radermacher P


Labels: MiParea: Respiration, mt-Medicine  Pathology: COPD 

Organism: Mouse  Tissue;cell: Heart, Skeletal muscle, Lung;gill  Preparation: Homogenate 


Coupling state: ET  Pathway: NS  HRR: Oxygraph-2k 

MiP2013 

Figure

Figure 1: Maximum mitochondrial respiration in homogenised diaphragm (left) and heart biopsies (right; means±SD). Control (left bars) vs. MV (right bars) in wildtype (WT) and cigarette smoke exposed (CSE) mice.


Affiliations and author contributions

Dept of Anesthesia, Section of Anesthesiological Pathophysiology and Process Development, Ulm University, Germany

Email: jose.matallo@uni-ulm.de

References

  1. Levine S, Nguyen T, Taylor N, Friscia ME, Budak MT,Rothenberg P, Yhu J, Sachdeva R, Sonnad Sm Kaiser LR, Rubinstein NA, Powers SK, Shrager JB (2008) Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med 358: 1327-1335.
  2. Kavazis AN, Talbert EE, Smuder AJ, Hudson MB, Nelson WB, Power SK (2009) Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production. Free Radic Biol Med 46: 842-850.
  3. Picard M, Jung B, Liang f, Azuelos I, Hussain S, Goldberg P, Godin R, Danialou G, Chaturvedi R, Rygiel K, Matecki S, Jaber S, Des Rosiers C, Karpati G, Ferri L, Burelle Y, Turnbull DM, Taivassalo T, Petrof BJ (2012) Mitochondrial dysfunction and lipid accumulation in the human diaphragm during mechanical ventilation. Am J Respir Crit Care Med 186: 1140–1149.
  4. Wagner F, Scheuerle A, Webwe S, Stahl B, McCook O, Knöferl MW, Huber-Lang M, Seitz DH, Thomas J, Asfar P, Szabó C, Möller P, Gebhard F, Georgieff M, Calzia E, Radermacher P, Wagner K (2011) Cardiopulmonary, histologic, and inflammatory effects of intravenous Na2S after blunt chest trauma-induced lung contusion in mice. J Trauma 71: 1659-1667.