INTRODUCTION: PLV with perfluorocarbons improves gas exchange after lung injury. We studied isolated piglet lungs devoid of systemic detractors to determine PVR as an index of lung injury. If PLV affects lung injury we asked a) if PLV alone affected PVR in uninjured lung, b) if PLV had prophylactic effect administered prior to injury, c) if PLV had therapeutic effect administered after injury, d) if prophylactic and therapeutic effects were different.METHODS: Neonatal piglet (3-4kg) lungs were preparedin situ without ischemia, hypoxia, or reperfusion injury. Prior to aortic/ductus ligation, pulmonary artery (PA) and left atrium(LA) were cannulated and attached to a perfusion circuit (flow = 80cc/kg/min, Hct=28%). Volume cycled ventilation was accomplished via tracheostomy. Normal blood gas parameters were maintained and monitored continuously. Ppa, Pla(mmHg) and Qpa (L/min) were recorded and PVR calculated(PVR=Ppa-Pla /Qpa). After a stable baseline with gas ventilation only, lungs were divided in three groups. Group I (n=7)(PLV alone)-endotracheal perfluorodecalin (15cc/kg) only. Group II(n=7) (prophylaxis)- endotracheal perfluorodecalin followed in 60 minutes by intravenous oleic acid (OA) at 0.08cc/kg. Group III (n=8)(therapeutic)- OA followed by perfluorodecalin and PVR was calculated after a 60 minute steady state. Results were expressed as mean ± SEM. Significance of differences were obtained by repeated measures ANOVA. RESULTS: Baseline PVR of normoxic gas ventilated animals was 127±19 mmHg/L/kg. Group I: PVR after PLV was 160±15 (p=ns vs. baseline). Group II: After OA infusion, PVR increased to 281±26 (p<.05 vs. baseline), but after 60 minutes PVR decreased to 193±19 (p=ns vs. initial baseline, p<.05 vs. OA). Group III: Sixty minutes after OA infusion, PVR increased from baseline to 318±41 (p<.01). Sixty minutes after administration of perfluorodecalin, PVR decreased significantly to 201±20 (p<.01 vs. OA, p=ns vs. baseline). PVR of Group II and Group III was not different(p=ns) after PLV administration CONCLUSIONS : a) Perfluorodecalin has no effect on PVR in the uninjured lung.b) Prophylactic administration of perfluorodecalin prevents the sustained increase of PVR ordinarily induced by OA injury. c) Therapeutically administered perfluorodecalin abates OA injury induced elevation in PVR. d) Prophylactic and therapeutic perfluorodecalin have similar effects on PVR in the OA injured lung.