Threshold estimation of ultrasound-induced lung hemorrhage in adult rabbits and comparison of thresholds in mice, rats, rabbits and pigs

Abstract

The objective of this study was to assess the threshold and superthreshold behavior of ultrasound (US)-induced lung hemorrhage in adult rabbits to gain greater understanding about species dependency. A total of 99 76 ± 7.6-d-old 2.4 ± 0.14-kg New Zealand White rabbits were used. Exposure conditions were 5.6-MHz, 10-s exposure duration, 1-kHz PRF and 1.1-μs pulse duration. The in situ (at the pleural surface) peak rarefactional pressure, p r(in situ), ranged between 1.5 and 8.4 MPa, with nine acoustic US exposure groups plus a sham exposure group. Rabbits were assigned randomly to the 10 groups, each with 10 rabbits, except for one group that had nine rabbits. Rabbits were exposed bilaterally with the order of exposure (left then right lung, or right then left lung) and acoustic pressure both randomized. Individuals involved in animal handling, exposure and lesion scoring were blinded to the exposure condition. Probit regression analysis was used to examine the dependence of the lesion occurrence on in situ peak rarefactional pressure and order of exposure (first vs. second). Likewise, lesion depth and lesion root surface area were analyzed using Gaussian tobit regression analysis. Neither probability of a lesion nor lesion size measurements was found to be statistically dependent on the order of exposure after the effect of p r(in situ) was considered. Also, a significant correlation was not detected between the two exposed lung sides on the same rabbit in either lesion occurrence or size measures. The p r(in situ) threshold estimates (in MPa) were similar to each other across occurrence (3.54 ± 0.78), depth (3.36 ± 0.73) and surface area (3.43 ± 0.77) of lesions. Using the same experimental techniques and statistical approach, great consistency of thresholds was demonstrated across three species (mouse, rat and rabbit). Further, there were no differences in the biologic mechanism of injury induced by US and US-induced lesions were similar in morphology in all species and age groups studied. The extent of US-induced lung damage and the ability of the lung to heal led to the conclusion that, although US can produce lung damage at clinical levels, the degree of damage does not appear to be a significant medical problem. (E-mail: wdo@uiuc.edu)