Hypoxia Due to Shunts in Pig Lung Treated with O₂ and Fluorocarbon-derived Intravascular Microbubbles

Abstract:

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. (1^st 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.

Keywords::

• Right-to-left pulmonary shunts
• fluorocarbons
• lung pathology
• oxygen therapy
• microbubbles
• ventilation-perfusion ratio
• blood gases
• athelectasis

Declaration of interest: Authors I. Tyssebotn and C. Lundgren are two of four inventors on US patents Nos. 6.127,428 and 5,869,538 pertaining to the use of micro-bubbles for enhancing circulatory gas transport in the body. These patents are owned by the Research Foundation (RF) of the State of N.Y. which has licensed the technology to a pharmaceutical company for commercialization. The inventors will receive part of any income received by the RF from the licensee.