Team 2 / Theme 4

Myopathy and complications induced by intensive care and Drapeau Françaisperioperative anesthesia

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.

Fig 1 Thème 4 EQ2Figure 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.

Fig 2 Thème 4 EQ2Figure 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.

Appareils de ventilation mécaniqueFig 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.

 

 

 


 Collaborations :

  • 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 :

under building

 

Coordinators :

Jaber Samir

Matecki Stéfan

Participants :

Lacampagne Alain

Jung Boris

Chanques Gérald

Klouche Kada