What is the clinical evidence from this study?

Study design: Other. Intervention: Anionic lipid microbubbles vs. Neutral lipid microbubbles. Primary outcome: Capillary retention of microbubbles (mm^-3) (p=<0.01).

What question did this study set out to answer?

To determine whether microbubble surface charge influences the microvascular retention of ultrasound contrast agents.

September 13, 2026Journal of the American College of CardiologyOpen Access

Influence of microbubble surface charge on capillary transit and myocardial contrast enhancement

Q: What are the key findings of this study?

Anionic lipid microbubbles demonstrated significantly greater capillary retention compared with neutral microbubbles (4.3 vs. 0.4 mm^-3, p < 0.01), mediated by complement attachment.

Q: What question did this study set out to answer?

To determine whether microbubble surface charge influences the microvascular retention of ultrasound contrast agents.

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Key result

Anionic microbubbles increase capillary retention ~10-fold over neutral microbubbles via complement attachment.

P<0.01
n=15

Population

6 wild-type mice, 3 C3-deficient mice, and 6 dogs

Comparison

Intravenous injection of lipid-shelled… vs Intravenous injection of lipid-shelled…

Design

Preclinical

Authors

NFNicholas G. FisherNelson Marlborough Institute of Technology JCJ. ChristiansenWaitemata District Health Board AKAlexander L. KlibanovUniversity of Virginia

Discussion

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Implication

Lipid microbubbles with a net negative charge are retained within capillaries via complement-mediated attachment to endothelium, which may be useful for developing ultrasound contrast agents for late imaging.

Key Points

To determine whether microbubble surface charge influences the microvascular retention of ultrasound contrast agents.
Conducted intravital microscopy of the cremaster muscle in six wild-type mice and three C3-deficient mice following intravenous injection of neutral or anionic lipid microbubbles, prepared with or without surface polyethyleneglycol (PEG).
Assessed complement C3b attachment to microbubbles via flow cytometry using fluorescein isothiocyanate-conjugated monoclonal antibodies.
Performed myocardial contrast echocardiography in six dogs to evaluate pulmonary and myocardial microbubble transit and retention.
Size-independent capillary retention occurred significantly more frequently with anionic microbubbles than with neutral microbubbles (4.3 ± 0.3 vs. 0.4 ± 0.1 mm⁻³, p < 0.01).
Retention of anionic microbubbles was reduced by 70% with surface PEG and significantly attenuated in C3-deficient mice (1.4 ± 0.1 mm⁻³, p < 0.05 vs. wild-type), with flow cytometry confirming complement attachment solely to anionic microbubbles.
Myocardial contrast echocardiography demonstrated pulmonary and myocardial retention exclusively for anionic microbubbles, marked by persistent myocardial opacification for >10 min after bolus intravenous injection.

Structured PICO

Population

15 animals (6 wild-type mice, 3 C3-deficient mice, and 6 dogs) undergoing intravital microscopy and myocardial contrast echocardiography.

Intervention

Intravenous injection of lipid-shelled microbubbles with a negative charge (anionic), prepared with and without a protective surface layer of polyethyleneglycol (PEG)

Comparator

Intravenous injection of lipid-shelled microbubbles with a neutral charge, prepared with and without a protective surface layer of polyethyleneglycol (PEG)

Outcome

Microvascular retention of microbubbles (capillary retention in cremaster muscle, pulmonary and myocardial retention)surrogate

Main Result

Absolute Event Rate: 4.3% vs 0.4%

p-value: p=<0.01

Cite This Study

Fisher et al. (2002) studied this question. Anionic lipid microbubbles vs. Neutral lipid microbubbles was evaluated on Capillary retention of microbubbles (mm^-3) (p=<0.01). Anionic lipid microbubbles demonstrated significantly greater capillary retention compared with neutral microbubbles (4.3 vs. 0.4 mm^-3, p < 0.01), mediated by complement attachment.

synapsesocial.com/papers/6aa66a76805167d96e050294 https://doi.org/10.1016/s0735-1097(02)02038-7

Topics

Echocardiography

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Influence of microbubble surface charge on capillary transit and myocardial contrast enhancement

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Topics

Influence of microbubble surface charge on capillary transit and myocardial contrast enhancement

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

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Topics

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