Microvascular behavior and effects of Sonazoid microbubbles in the cremaster muscle of rats after local administration

Objective. The purpose of this study was to observe Sonazoid perfluorobutane microbubbles (GE Healthcare, Amersham, Buckinghamshire, England) in and their effects on the cremaster capillary microcirculation of rats. Methods. Sonazoid (0.3 x 10(9) microbubbles in 0.5 mL) was observed by intravital microscopy in the cremaster muscle after retrograde administration into the femoral artery of 6 animals. Microbubble and microvessel diameters and blood flow velocities and the overall mean and 14 SD of the 1-minute volume flow through the microscopic field were calculated from the 2 to 4 capillaries observed in the field of each animal. Fluorescein isothiocyanate-dextran leakage was used to assess extravasation after microbubble passage. Results. A total of 331 bubbles of 2.4 to 3.1 mu m in median diameter were observed in 6 animals. Four bubbles (3.5-7.0 mu m) and a cluster of 4 bubbles (nominal diameter, 5.6 mu m) were plugging the observed capillaries for 18, 16, 7, 3, and 9 seconds, respectively, before they were released and capillary flow normalized. No microbubble size changes, damming, or coalescence of bubbles and no changes in microvessel diameter or microvascular blood A flow velocities, volume flow, or perfusion heterogeneity occurred during or after the passage of the Sonazoid suspension or the vehicle. No fluorescein isothiocyanate-dextran leakage was observed. Conclusions. The passage of Sonazoid bubbles at concentrations higher than those expected after intravenous administration of the Sonazoid did not durably impair microvascular perfusion, structural integrity, or macromolecular retention in the rat cremaster muscle. The duration of discrete capillary obstructions was short and in all cases comparable with that of naturally occurring leukocyte plugging.