Objective: Controlled mechanical ventilation leads to diaphragmatic contractile dysfunction and atrophy. Since proteolysis is enhanced in the diaphragm during controlled mechanical ventilation, we examined whether the administration of a proteasome inhibitor, bortezomib, would have a protective effect against ventilator-induced diaphragm dysfunction. Design: Randomized, controlled experiment. Settings: Basic science animal laboratory. Interventions: Anesthetized rats were submitted for 24 hrs to controlled mechanical ventilation while receiving 0.05 mg/kg bortezomib or saline. Control rats were acutely anesthetized. Measurements and Main Results: After 24 hrs, diaphragm force production was significantly lower in mechanically ventilated animals receiving an injection of saline compared to control animals (−36%, p < .001). Importantly, administration of bortezomib improved the diaphragmatic force compared to mechanically ventilated animals receiving an injection of saline (+15%, p < .01), but force did not return to control levels. Compared to control animals, diaphragm cross-sectional area of the type IIx/b fibers was significantly decreased by 28% in mechanically ventilated animals receiving an injection of saline (p < .01) and by 16% in mechanically ventilated animals receiving an injection of bortezomib (p < .05). Diaphragmatic calpain activity was significantly increased in mechanically ventilated animals receiving an injection of saline (+52%, p < .05) and in mechanically ventilated animals receiving an injection of bortezomib (+36%, p < .05). Caspase-3 activity was increased after controlled mechanical ventilation with saline by 55% (p < .05), while it remained similar to control animals in mechanically ventilated animals receiving an injection of bortezomib. Diaphragm 20S proteasome activity was slightly increased in both ventilated groups, and the amount of ubiquitinated proteins was significantly and similarly enhanced in mechanically ventilated animals receiving an injection of saline and mechanically ventilated animals receiving an injection of bortezomib. Conclusions: These data show that the administration of bortezomib partially protects the diaphragm from controlled mechanical ventilation–induced diaphragm contractile dysfunction without preventing atrophy. The fact that calpain activity was still increased after bortezomib treatment may explain the persistence of atrophy. Part of bortezomib effects might have been due to its ability to inhibit caspase-3 in this model.

Bortezomib partially protects the rat diaphragm from ventilator-induced diaphragm dysfunction

Introduction : La neuromyopathie acquise en reanimation est une complication frequente avec des repercussions sur le sevrage respiratoire et la duree de sejour en reanimation. Elle est diagnostiquee par un score MRC 
Materiel et methode : Il s’agit d’une etude prospective, observationnelle, monocentrique, realisee dans un service de reanimation polyvalente. Les patients ayant un score Apache II > 13 et ventiles plus de 48 h sont inclus de maniere consecutive. Nous realisons des echographies musculaires au niveau des quadriceps a J2, J7 et J14 : la masse musculaire est estimee en mesurant l’aire de section transversale du muscle droit anterieur et vaste intermediaire. Il y a 3 sites de mesures par quadriceps : proximal, medial et distal. Les patients n’ayant pas eu d’echographie musculaire a J7 sont exclus. Nous realisons egalement des echographies diaphragmatiques avec mesure du temps d’excursion diaphragmatique en VSAI, lors de l’epreuve de VSNA et lors de l’extubation. Le score MRC est mesure a la sortie de reanimation. Les patients sont revus a 6 mois avec mesure du score MRC et du SF36. Le critere de jugement principal est la fonte musculaire la premiere semaine de reanimation : difference absolue entre les echographies musculaires de J2 et de J7. La rehabilitation etait celle effectuee habituellement par les kinesitherapeutes du service avec utilisation de cycloergometre et d’EMS. 
Resultats : 64 patients ont ete inclus de septembre 2016 a fevrier 2017 et 55 patients ont pu etre analyses. Il existe une fonte musculaire significative des quadriceps de J2 a J7 avec une difference absolue de -0.3 cm en proximal (p = 0.02), de -0.4cm en medial (p = 0.0004) et de -0.1cm en distal (p = 0.015). Il n’y a pas de relation significative entre la fonte musculaire et les techniques de rehabilitation ni avec le score MRC de sortie. Le temps d’excursion diaphragmatique augmente significativement au cours des etapes du sevrage respiratoire. 
Conclusions : La fonte musculaire existe de maniere precoce, des J7. L’echographie musculaire du quadriceps femoral realise en position mediale a mi-cuisse en est un bon marqueur pour le diagnostic et le suivi.

https://dumas.ccsd.cnrs.fr/dumas-01634969/document

Analyses échographiques de l'évolution de la masse musculaire et du diaphragme en réanimation

Efectos de la rehabilitación pulmonar en el paciente en estado crítico. Revisión de la literatura

Réhabilitation précoce d’un patient vigile sous assistance circulatoire extracorporelle veino-artérielle périphérique : étude de cas

Efectos de la sarcopenia en el paciente en cuidado crítico durante ventilación mecánica prolongada

Resume Introduction La ventilation mecanique est associee a une dysfonction diaphragmatique (DDIV) chez l’animal comme chez l’homme. Etat des connaissances Les mecanismes physiopathologiques sont intimement lies a l’absence d’activite musculaire des muscles respiratoires mais egalement secondaires a l’utilisation de hauts niveaux de volume courant et se potentialisent avec d’autres sources d’agression systemique (medicaments, infection, denutrition, hypoperfusion…). Augmentation du stress oxydant, instabilite membranaire et activation des voies de signalisation cellulaire impliquant la proteolyse exageree, diminution de la synthese proteique, autophagie et decouplage excito-contraction se potentialisent pour aboutir a la DDIV. L’exploration de la DDIV au lit du patient peut etre realisee sans la participation de ce dernier, a l’aide d’une stimulation phrenique magnetique cervicale ou faire appel a la participation du patient a l’aide d’une exploration fonctionnelle respiratoire ou d’une echographie diaphragmatique. Conclusion et perspectives Chez l’homme, seule la persistance des cycles ventilatoires spontanes et peut-etre la stimulation des nerfs phreniques semblent a ce jour diminuer la severite de la DDIV. D’autres voies therapeutiques pharmacologiques specifiques sont en cours d’investigation chez l’animal.

Conséquences de la ventilation mécanique sur le diaphragme

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Conséquences de la ventilation mécanique sur le diaphragme