Grant: Project Grant

Mechanical ventilation (MV) of critically ill patients with severe acute lung injury is a life-saving procedure. The precise way to deliver MV is very complex and needs guidance because of the numerous risks associated with an inadequate delivery. An optimal ventilation should protect the lungs, the respiratory muscles, and the brain of the patients to reduce the short term and long term complications of MV. MV applies the same pressure everywhere in the lung. However, the lung is heterogeneous and the airways and the lung regions do not open at the same time and with the same pressure, due to the effect of gravity on inflammatory lungs, aggravated by anesthesia and bed rest and the frequent asymmetry of injury. Part of the lungs are at risk of distension and of further injury, while other parts remain collapsed if insufficient pressure is applied. The use of MV rapidly results in atrophy of the respiratory muscles, unable to reopen the lungs. Lastly, there is a lung-brain circuit that results in brain injury and can explain the long-term neurocognitive complications frequently observed after MV. Lats, we have shown that insufficient reopening of the lung makes the work of the heart very difficult and we want to understand the mechanisms. We therefore propose a series of experiments in pre-clinical models of acute lung injury to address these knowledge gaps and propose innovative solutions than can help to better treat patients with acute respiratory failure. We will explore ventilation and perfusion using a new technique (Electrical Impedance Tomography), giving regional distribution images in real time. We will perform Magnetic Resonance Imaging of the lungs, brain and diaphragm, to study diaphragm and lung function. We will study how to maintain airways open, balance the need for recruiting the lung and minimizing distension and will use an innovative technique stimulating the phrenic nerve to preserve diaphragm function as well as preserving lung and brain.