The mechanisms and pathophysiological changes associated with ventilator-induced lung injury are unclear. We used a combined experimental-mathematical model approach to quantify the abnormalities in pulmonary mechanics associated with ventilator-induced lung injury in rabbits.
New Zealand white rabbits were anesthetized and ventilated for up to 5 hours using a digitally-controlled ventilator (flexiVent, Scireq, Montreal, Canada). The ventilator can apply broadband perturbations in flow to the lungs to assess pulmonary mechanics. Measurements were made every 30 minutes of lung resistance, lung compliance, oscillation mechanics (impedance), and the pressure-volume relationship. Continuous records were made of end-tidal PCO2, arterial O2 saturation (pulse oxymetry), heart rate, arterial blood pressure, and body temperature. Arterial blood gases/pH were analyzed routinely. The data were analyzed using mathematical models of pulmonary mechanics and gas exchange developed in our laboratory (J Appl Physiol 84:1447-69, 1998; J Biol Sys 8:115-39, 2000). These models use nonlinear characterizations of airway resistance, airway and chest wall compliance, and lung tissue viscoelasticity.
Increasing tidal volume from 6 ml/kg to 25 ml/kg for 4 hours was accompanied by progressive increments in lung resistance and decrements in lung compliance. These effects primarily reflected actions on the lung parenchyma, as evidenced by changes in tissue damping and elastance over airway (Newtonian) resistance. In contrast, administration of methacholine caused a rapid transient increase in lung resistance and fall in compliance. These effects primarily reflected actions on the airway, as evidenced by changes in airway resistance over tissue viscoelastic properties.CONCLUSIONS: A combined experimental-mathematical model approach has been used to separate airway and parenchymal abnormalities during the development of acute lung injury, and to quantify the degree and time course of the abnormalities.
Ventilatory strategy may have important effects on both the development and time course of abnormalities in lung function during mechanical ventilation.
T.A. Heming, None.