PARTIAL LIQUID VENTILATION REDUCES PULMONARY NEUTROPHIL ACCUMULATION IN AN EXPERIMENTAL-MODEL OF SYSTEMIC ENDOTOXEMIA AND ACUTE LUNG INJURY

Objective: To determine whether pulmonary neutrophil se questration an d lung injury are affected by partial liquid ventilation with perfluor ocarbon in a model of acute lung injury (ALI). Design: A prospective, controlled, in vivo animal laboratory study. Setting: An animal resear ch facility of a health sciences university. Subjects: Forty one New Z ealand White rabbits. Interventions: Mature New Zealand White rabbits were anesthetized and instrumented with a tracheostomy and vascular ca theters. Animals were assigned to receive partial liquid ventilation ( PLV, n = 15) with perflubron (18 mL/kg via endotracheal tube), convent ional mechanical ventilation (CMV, n = 15) or high frequency oscillato ry ventilation (HFOV, n = 5). Animals were ventilated, using an Flo(2) of 1.0, and ventilatory settings were required to achieve a normal Pa co(2). Animals were then given 0.9 mg/kg of Escherichia coil endotoxin intravenously over 30 mins. Partial liquid ventilation, conventional mechanical ventilation, or high-frequency oscillatory ventilation was continued for an additional 4 hrs before the animals were killed. A gr oup of animals not challenged with endotoxin underwent conventional ve ntilation for 4.5 hrs, serving as the control group (control, n = 6). Lungs were removed and samples were frozen at -70 degrees C. Represent ative samples were stained for histology. A visual count of neutrophil s per high power field (hpf) was performed in five randomly selected f ields per sample in a blinded fashion by light microscopy. Lung sample s were homogenized in triplicate in phosphate buffer, ultrasonified, f reeze thawed, and clarified by centrifugation. Supernatants were analy zed for myeloperoxidase (MPO) activity by spectrophotometry with odian isidine dihydrochloride and hydrogen peroxide at 460 nm. Measurements and Main Results: Histologic analysis of lung tissue obtained from con trol animals showed normal lung architecture. Specimens from the PLV a nd HFOV groups showed a marked decrease in alveolar proteinaceous flui d, pulmonary vascular congestion, edema, necrotic cell debris, and gro ss inflammatory infiltration when compared with the CMV group. Light m icroscopy of lung samples of animals supported with PLV and HFOV had s ignificantly lower neutrophil counts when compared with CMV (PLV, 4 +/ - 0.3 neutrophils/hpf; HFOV, 4 +/- 0.5 neutrophils/hpf; CMV, 10 +/- 0. 9 neutrophils/hpf; p<.01). In addition, MPO activity from lung extract s of PLV and HFOV animals was significantly lower than that of CMV ani mals (PLV, 61 +/- 13.3 units of MPO activity/lung/kg; HFOV, 43.3 +/- 6 .8 units of MPO activity/lung/kg; CMV, 140 +/- 28.5 units of MPO activ ity/lung/kg; p<.01). MPO activity from lungs of uninjured control anim als was significantly lower than that of animals in the PLV, HFOV, and CMV groups (control, 2.2 +/- 2 units of MPO activity/lung/kg; p<.001) . Conclusions: Partial liquid ventilation decreases pulmonary neutroph il accumulation, as shown by decreased neutrophil counts and MPO activ ity, in an experimental animal model of ALI induced by systemic endoto xemia. The attenuation in pulmonary leukostasis in animals treated wit h PLV is equivalent to that obtained by a ventilation strategy that ta rgets lung recruitment, such as HFOV.