Suitable solutions for reconstituting the ultrasound contrast agent "Levovist" used in contrast echocardiogram: in vitro and in vivo evaluation of the influence of osmotic pressure

Abstract

Purpose: To evaluate the influence of the osmotic pressure of solutions used for reconstituting the ultrasound contrast agent "Levovist" on the degree of video intensity of the enhancement and video intensity decay in contrast echocardiogram, we used 6 solutions with different osmotic pressures in both vitro and in vivo experiments.

Materials and methods: In the in vitro experiments, Levovist was reconstituted with 6 kinds of solutions with different osmotic pressures (Lactate Ringer's solution, 2.5%, 5%, 7.5%, and 20% glucose and distilled water) and peak video intensities and video intensity decay were measured. In the in vivo experiments, contrast echocardiography was performed in 7 adult volunteers, following the intravenous injections of Levovist, previously reconstituted with one of 2 solutions (5% glucose or distilled water).

Results: In vitro, at peak time, Levovist reconstituted with either Lactate Ringer's solution, 2.5% glucose, 5% glucose, or distilled water had good peak video intensities. At 30 s after peak time, Levovist reconstituted with Lactate Ringer's solution had greater enhancement and less decay than the other 5 solutions (P<0.001). In vivo, at 180 heart beats after peak time, the video intensity decay with 5% glucose was greater than that with distilled water (150+/-13 dB, 123+/-25 dB, respectively, P<0.05).

Conclusion: In this study, among various (2.5-20%) glucose solutions, the stability of the microbubbles differed, depending on the degree of osmotic pressure of the respective solutions; 5% glucose was the best. However, overall, the most suitable solution for reconstituting Levovist, was Lactate Ringer's solution. These findings could lead to effective strategies for better contrast echocardiography using Levovist by changing the current solution of choice to Lactate Ringer's solution or 5% glucose.