Table 2 Lessons learned from experimental studies and future experimental objectives
From: Understanding the mechanisms of ventilator-induced lung injury using animal models
What is known? | Mechanisms to be explored with preclinical research |
|---|---|
Increased Ppeak,RS can impair heart–lung interaction | Microvascular injury mechanism followed by increased permeability to water, proteins, or even cells Improve methods or techniques to non-invasively monitor pulmonary vascular dynamics (echocardiography, electrical impedance tomography, among others) Easily identify conditions for the risk of lung injury |
Pplat,RS, between 20 and 25 cmH2O, is associated with epithelial and endothelial cell damage as well as increased permeability | Further development of participation of interstitial compartment modeling, according to Pplat,RS levels Development of permeability markers to be used in preclinical studies with potential to be used in clinical studies, according to Pplat,RS levels Further explore the participation of the chest wall in different scenarios, such as obesity, pneumoperitoneum, and abdominal compartment syndromes |
Low PEEP levels may not be sufficient to prevent alveolar collapse and lung edema, whereas high PEEP may cause lung overdistention and hemodynamic impairment | Further evaluate the effect of PEEP in a “personalized approach” taking into account individual lung mechanics, imaging, and/or ARDS phenotypes |
The static, but not dynamic, ΔP,L represents the main determinant of lung injury | Evaluate the diaphragm and cardiovascular consequences of increased and decreased levels of ΔP,L What are the biotrauma consequences of increasing levels of ΔP,L Further evaluate ΔP,L during spontaneous breathing, because it can be very high and it is considered one of the mechanisms of P-SILI |
Epithelial, endothelial cells, and the extracellular matrix of the lung may adapt to increasing levels of VT | At the micro-scale, further evaluate the adaptation of structural cells to static and cyclic stretch, associated or not with endotoxin Study the increasing VT taking into account the mechanical power and cumulative mechanical power generated, by changing the time under MV Evaluate alveolar-capillary barrier resolution and how lipids and water accommodate increasing VT |
Gradually increasing respiratory rate may be beneficial for abrupt increases with regard to lung aeration and accommodation of stress for the same VT | Further investigate if the lung damage after abrupt increases in RR is dependent on alveolar heterogeneity at baseline Investigate the importance of mechanical power measured within 1 min and the cumulative mechanical power within a long time scale Confirm whether a threshold of transition to injury exists to precisely determine the pace of gradually increasing RR Refinement by imaging studies that show in real time what happens to the number of fast alveolar units |
High inspiratory flows and flow profiles may be associated with lung damage | At micro-scale, evaluate the mechanosensing and transduction of shear stress on structural cells and how they may adapt depending on the magnitude and profiles Evaluate heart–lung interaction under increased magnitude of airflow because it can also increase Ppeak,RS |
Mechanical power is associated with VILI | Mechanical power, cumulative mechanical power, intensity – which is the best predictor of VILI? |