The effects of the microbubble suspension SH U 454 (Echovist) on ultrasound-induced cell lysis in a rotating tube exposure system.
Human erythrocytes resuspended at different hematocrits in autologous plasma at 37 degrees C were exposed to the therapeutic intensities of continuous-wave 0.75-MHz ultrasound in vitro in a rotating tube exposure apparatus designed to maximize the destructive effects of cavitational activity. Provided that large numbers of additional gas bubbles had not been introduced during the various preparative and manipulatory procedures, the addition of Echovist at final concentrations comparable with those currently being used for clinical investigations resulted in a statistically significant increase in the amount of cell lysis in vitro in those samples having hematocrits less than 2%. The amount of cell lysis produced at any given ultrasound intensity decreased with increasing hematocrit in both the controls and the cell suspensions containing Echovist until it was virtually zero in both cases at hematocrits of 5.5% or greater. The addition of Echovist to samples that already contained large numbers of stabilized gas bubbles and/or had hematocrits greater than 5.5% produced no detectable cell lysis even at ultrasonic intensities as high as 3 W/cm 2 spatial average, temporal average (SATA). It is therefore unlikely that Echovist would cause appreciable amounts of cell lysis when the gas bubbles were being exposed to ultrasound under the conditions used for clinical investigations in vivo.