Effects of vascular flow and PEEP in a multiple hit model of lung injury in isolated perfused rabbit lungs.

BACKGROUND: High vascular flow aggravates lung damage in animal models of ventilator-induced lung injury. Positive end-expiratory pressure (PEEP) can attenuate ventilator-induced lung injury, but its continued effectiveness in the setting of antecedent lung injury is unclear. The objective of the present study was to evaluate whether the application of PEEP diminishes lung injury induced by concurrent high vascular flow and high alveolar pressures in normal lungs and in a preinjury lung model. METHODS: Two series of experiments were performed. Fifteen sets of isolated rabbit lungs were randomized into three groups (n = 5): low vascular flow/low PEEP; high vascular flow/low PEEP, and high vascular flow/high PEEP. Subsequently, the same protocol was applied in an additional 15 sets of isolated rabbit lungs in which oleic acid was added to the vascular perfusate to produce mild to moderate lung injury. All lungs were ventilated with peak airway pressure of 30 cm H2O for 30 minutes. Outcome measures included frequency of gross structural failure, pulmonary hemorrhage, edema formation, changes in static compliance, pulmonary vascular resistance, and pulmonary ultrafiltration coefficient. RESULTS: In the context of high vascular flow, application of a moderate level of PEEP reduced pulmonary rupture, edema formation, and lung hemorrhage. The protective effects of PEEP were not observed in lungs concurrently injured with oleic acid. CONCLUSIONS: Under these experimental conditions, PEEP attenuates lung injury in the setting of high vascular flow. The protective effect of PEEP is lost in a two-hit model of lung injury.

Contributions of vascular flow and pulmonary capillary pressure to ventilator-induced lung injury.

OBJECTIVE: To evaluate the influence of vascular flow on ventilator-induced lung injury independent of vascular pressures. DESIGN: Laboratory study. SETTING: Hospital laboratory. SUBJECTS: Thirty-two New Zealand White rabbits. INTERVENTIONS: Thirty-two isolated perfused rabbit lungs were allocated into four groups: low flow/low pulmonary capillary pressure; high flow/high pulmonary capillary pressure; low flow/high pulmonary capillary pressure, and high flow/low pulmonary capillary pressure. All lungs were ventilated with peak airway pressure 30 cm H2O and positive end-expiratory pressure 5 cm H2O for 30 mins. MEASUREMENTS AND MAIN RESULTS: Outcome measures included frequency of gross structural failure (pulmonary rupture), pulmonary hemorrhage, edema formation, changes in lung compliance, pulmonary vascular resistance, and pulmonary ultrafiltration coefficient. Lungs exposed to high pulmonary vascular flow ruptured more frequently, displayed more hemorrhage, developed more edema, suffered larger decreases in compliance, and had larger increases in vascular resistance than lungs exposed to low vascular flows (p < .05 for each pairwise comparison between groups). CONCLUSIONS: These findings suggest that high pulmonary vascular flows might exacerbate ventilator-induced lung injury independent of their effects on pulmonary vascular pressures.