High in comparison with low tidal volume ventilation aggravates oxidative stress-induced lung injury

Abstract

Ventilator settings influence the development and outcome of acute lung injury. This study investigates the influence of low versus high tidal volume ( V t) on oxidative stress-induced lung injury. Isolated rabbit lungs were subjected to one of three ventilation patterns ( V t–positive end-expiratory pressure, PEEP): LVZP (6 ml/kg–0 cm H 2O), HVZP (12 ml/kg–0 cm H 2O), LV5P (6 ml/kg–5 cm H 2O). These ventilation patterns allowed a comparison between low and high V t without dependence on peak inspiratory pressure (PIP). Infusion of hypochlorite (1000 nmol/min) or buffer (control) was started at t=0 min. Pulmonary artery pressure (PAP), PIP and weight were continuously recorded. Capillary filtration coefficient [ K f,c (10 −4 ml s −1 cm H 2O −1 g −1)] was gravimetrically determined (−15/30/60/90/120 min). PIP averaged 5.8±0.6/13.9±0.6/13.9±0.4 cm H 2O in the LVZP, HVZP and LV5P groups. PIP, K f,c or PAP did not change in control groups, indicating that none of the ventilation patterns caused lung injury by themselves. Hypochlorite-induced increase in K f,c but not hypochlorite-induced increase in PAP, was significantly attenuated in the LVZP-/LV5P- versus the HVZP-group ( K f,c,max. 1.0±0.23/1.4±0.40 versus 3.2±1.0*). Experiments with hypochlorite were terminated due to excessive edema (>50 g) at 97±2.2/94.5±4.5 min in the LVZP-/LV5P-group versus 82±3.8* min in the HVZP-group (*: P<0.05). Low V t attenuated oxidative stress-induced increase in vascular permeability independently from PIP and PEEP.