Intensive care presents several constraints on peripheral and respiratory muscle such as unloading, mechanical ventilation, drug toxicity or sepsis, leading to major contractile dysfunction. This myopathy, characterized by the presence of atrophy and injury, is generally observed in 50 % of patient in ICU and is involved in the duration increase of hospitalization, in the difficulty of weaning from mechanical ventilator support, in the increase of comorbidity and mortality, which have a high impact in the increase in health expenditure.
Figure 1 : Long term mechanical ventilation induce diaphragm atrophy and weakness associated with proteolysis in Human.
Moreover this myopathy persists several months after the ICU exit becoming a real chronic disease poorly undertaken. Physiopathological mechanisms involved in this myopathy are poorly understood and at the moment no preventive or curative treatments exist. Thus muscular evaluation during and after ICU stay is not standardized and not usually performed. Our objective is to focus on early physiopathological events involved in muscle dysfunction in order to identify new therapeutical targets.
Figure 2 : A ventilatory mode which induces diaphragm inactivity (CMV) compared to a ventilatory mode which preserve Diaphragm activity (ASV) is responsible of diaphragm atrophy and weakness in a model of ventilated pig.
Our research employs both experimental animal models of intensive care as well as human investigations in collaboration with ICU of Montpellier University hospital.
We focus on oxidative stress initiation secondary to unloading, mechanical stress or drug toxicity, and its link with calcium homeostasis impairment. Indeed calcium flux deregulation may affect excitation coupling contraction, contractile protein calcium sensitivity and trigger the main calcium dependent proteolytic pathways, involved in myopathy induced by intensive care and anesthesia.
Fig 3 : Different type of apparatus of mechanical ventilation with an artificial lung.
Our methods use technics that range from in vivo to in vitro contractile function evaluation in peripheral and respiratory muscles, biochemistry, mitochondrial function evaluation and calcium imaging in animal model as well as in humans.
- Critical Care and Anesthesia department of University hospital of Montpellier, France.
- Pr Basil Petrof, Mc Guil University, Montreal, Canada
- Pr Andy Marks, Columbia University, New York
- Dr Yannaël COISEL Département : Anesthésie-Réanimation Saint Eloi Montpellier
- Audrey De JONG (Doctorante CBS2, Département : Anesthésie-Réanimation Saint Eloi Montpellier)
Major Publications :
- De Jong A, Molinari N, Pouzeratte Y, Verzilli D, Chanques G, Jung B, Futier E, Perrigault PF, Colson P, Capdevila X, Jaber S. (2015). “Difficult intubation in obese patients: incidence, risk factors, and complications in the operating theatre and in intensive care units. “ Br J Anaesth. 114(2):297-306.
- Dessap AM, Katsahian S, Roche-Campo F, Varet H, Kouatchet A, Tomicic V, Beduneau G, Sonneville R, Jaber S, Darmon M, Castanares-Zapatero D, Brochard L, Brun-Buisson C. (2014). “Ventilator-associated pneumonia during weaning from mechanical ventilation: role of fluid management. “ Chest. 146(1):58-65.
- Jung B, Nougaret S, Conseil M, Coisel Y, Futier E, Chanques G, Molinari N, Lacampagne A, Matecki S, Jaber S. (2014). “Sepsis Is Associated with a Preferential Diaphragmatic Atrophy: A Critically Ill Patient Study Using Tridimensional Computed Tomography. “ Anesthesiology, 120(5):1182-91. (IF=5.16).
- Vaschetto R, De Jong A, Conseil M, Galia F, Mahul M, Coisel Y, Prades A, Navalesi P, Jaber S. (2014) “Comparative evaluation of three interfaces for non-invasive ventilation: a randomized cross-over design physiologic study on healthy volunteers.” Critical Care 2014, 18:R2.
- Jung B, Sebbane M, Le Goff C, Rossel N, Chanques G, Futier E, Constantin JM, Matecki S, Jaber S. (2013).”Moderate and prolonged hypercapnic acidosis may protect against ventilator-induced diaphragmatic dysfunction in healthy piglet: an in vivo study. ” Crit Care. 17(1):R15.
- Jaber S, Petrof BJ, Jung B, Chanques G, Berthet JP, Rabuel C, Bouyabrine H, Courouble P, Koechlin-Ramonatxo C, Sebbane M, Similowski T, Scheuermann V, Mebazaa A, Capdevila X, Mornet D, Mercier J, Lacampagne A, Philips A, Matecki S. (2013).”Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans. ” Am J Respir Crit Care Med. 183(3):364-71.
- Hussain SN, Mofarrahi M, Sigala I, Kim HC, Vassilakopoulos T, Maltais F, Bellenis I, Chaturvedi R, Gottfried SB, Metrakos P, Danialou G, Matecki S, Jaber S, Petrof BJ, Goldberg P. (2010).”Mechanical ventilation-induced diaphragm disuse in humans triggers autophagy. ” Am J Respir Crit Care Med. 182(11):1377-86.
- Jung B, Constantin JM, Rossel N, Le Goff C, Sebbane M, Coisel Y, Chanques G, Futier E, Hugon G, Capdevila X, Petrof B, Matecki S, Jaber S. (2010). .”Adaptive support ventilation prevents ventilator-induced diaphragmatic dysfunction in piglet: an in vivo and in vitro study.” Anesthesiology. 112(6):1435-43.