Hemodynamic Effects of Lipid-Based Oxygen Microbubbles via Rapid Intravenous Injection in Rodents

• Published in: Pharmaceutical research 2017-10, Vol.34 (10), p.2156-2162
• Main Authors: Black, Katherine J., Lock, Andrew T., Thomson, Lindsay M., Cole, Alexis R., Tang, Xiaoqi, Polizzotti, Brian D., Kheir, John N.
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Blood pressure; Blood Pressure - drug effects; Cholesterol; Cholesterol - chemistry; Circulatory system; Emulsions; Headspace; Health aspects; Heart; Heart diseases; Hemodynamics; Humans; Hypoxemia; Hypoxia - physiopathology; Hypoxia - therapy; Incidence; Injection; Injections, Intravenous; Intravenous administration; Male; Mechanical ventilation; Medical Law; Microbubbles; Morbidity; Oxygen; Oxygen - chemistry; Oxygen - metabolism; Packaging; Particle Size; Personal video recorders; Pharmacology/Toxicology; Pharmacy; Phosphatidylcholines - chemistry; Pulmonary arteries; Pulmonary artery; Pulmonary Artery - drug effects; Pulmonary Artery - physiopathology; Rats; Rats, Sprague-Dawley; Research Paper; Respiration, Artificial; Rodents; Surface Properties; Vascular Resistance
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-017-2222-3

Purpose Low oxygen levels, or hypoxemia, is a common cause of morbidity and mortality in critically ill patients. Hypoxemia is typically addressed by increasing the fraction of inspired oxygen, the use of mechanical ventilation, or more invasive measures. Recently, the injection of oxygen gas directly into the bloodstream by packaging it within lipid-based oxygen microbubbles (LOMs) has been explored. The purpose of this work is to examine the acute hemodynamic effects of intravenous injections of LOMs. Methods LOMs composed of 1,2-distearoyl-sn-glycero-3-phosphocoline and cholesterol were manufactured using a process of shear homogenization under an oxygen headspace. A 5 mL aliquot of either PlasmaLyte A, or low (37%) or high (55%) concentration LOMs ( n  = 10 per group) was injected over a 1 min period into Sprague Dawley rats instrumented for measurement of cardiac index and pulmonary (PVR) and systemic (SVR) vascular resistance during a 60 min observation period. Hemodynamics were compared between groups by linear mixed modeling. Results Approximately 10 11 LOMs with mean diameter 3.77 ± 1.19 μm were injected over the 1 min period. Relative to controls, rodents treated with high concentration LOMs exhibited a higher pulmonary artery pressure (20 ± 0.4 mmHg vs 18 ± 0.4 mmHg, P