Low sensitivity of measurements of respiratory mechanics in detecting lung edema from high tidal volume mechanical ventilation

Introduction

High tidal volume mechanical ventilation (HTVMV) leads to pulmonary edema from increased endothelial permeability. The lungs show evidence of inflammation with endothelial adhesion molecule expression, infiltrates of white blood cells and cytokine production. In order to understand the molecular mechanisms responsible for the pathogenesis of ventilator injury, mouse models are beneficial but technically difficult due to the small size of the animal. To study the time course of lung edema formation we compared lung elastance measured by forced oscillations with invasive methods of lung edema detection (for example, wet–dry weight ratio and histology).

Methods

C57Black6 mice were anesthetized with i.p. sodium pentothal and paralyzed with succinylcholine. A tracheostomy was performed and the animals were connected to a Flexivent ventilator (Sqirec). The HTVMV group received a tidal volume of 25 ml/kg and 33 breaths/minute for 4 hours. The control group received 7 ml/kg at 120 breaths/minute. Temperature was kept at 36–37°C with the aid of a heated pad. The heart rate was monitored with surface EKG electrodes. Lung elastance and tissue energy dissipation were measured every 30 minutes using the forced oscillation technique. At the end of the experiment a sternotomy was performed. A ligature was placed around the right hilum and the right lung was cut, briefly rinsed in PBS, blotted dry and weighed. The dry weight was obtained following desiccation at 60°C for 48 hours. The left lung was inflated with 500 μl formalin injected slowly into the tracheal canula and embedded in paraffin. Paraffin blocks were sectioned with a microtome at 5 μm thickness and stained with hematoxylin–eosin.

Results

The wet-to-dry weight ratios rose from 4.82 ± 0.16 in control animals to 6.34 ± 0.83 in the HTVMV group (P < 0.05, n = 4). Light microscopic examination of histologic sections showed mononuclear white cell infiltrates around small arteries and within the alveolar walls of mice in the HTVMV group but not in control mice. Elastance rose nonsignificantly during the HTVMV protocol.

Conclusion

In this in vivo mouse model, high tidal volume mechanical ventilation caused pulmonary edema and lung tissue infiltration with white blood cells. However, measurements of lung mechanics showed minimal changes during the course of the experiment, indicating that they are less useful in detecting early edema.