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Rationale: Earlier work has shown that experimental conditions calling for improved tissue oxygenation could be assisted by i.v. infusion of a dodecafluoropentane emulsion (DDFPe) forming oxygen-transporting microbubbles. Objectives: The present work investigated the effect of DDFPe on hypoxia due to experimental shunts in the pig lung. Methods: Nineteen O2 breathing, anesthetized pigs had glass beads administered into the trachea so as to significantly depress arterial oxygen tension (PaO2). PaO2 was recorded for up to 12 hrs while 0.1 ml/kg DDFPe was administered 1–3 times. Main Results: The animals were divided into two groups based on arterial oxygen saturation (SaO2) after shunt induction, combined with oxygen breathing: the “SaO2 >90% group” (n=6) and the “SaO2 <90% group” (n=13). In the “SaO2 <90% group,” the PaO2 increased stepwise with each infusion from 56.6±2.9 to 88.6±14.6 mmHG (P≤0.001); improvements lasted about 2 hrs after each infusion. Mixed venous oxygenation also increased with the infusions, e.g. (1st infusion) from a PvO2 of 41.4±2.3 to 49.9±4.2 mmHg (P≤0.05) and SvO2 58.0±2.9% (P≤0.01), the venous changes supporting arterial oxygenation. At the same time, arterial CO2 levels fell. Arterial O2 and CO2 levels were paralleled by similar changes in muscle tissue. Pulmonary arterial pressures did not indicate any pulmonary embolization by bubbles. Toxic effects of the treatment were not observed. Conclusion: These results suggest that, on condition of successful toxicity testing, intravascular administration of a DDFPe and oxygen breathing may be beneficial in severe right-to-left shunting in humans. [ABSTRACT FROM AUTHOR]