Threshold Estimation and Superthreshold Behavior of Ultrasound-Induced Lung Hemorrhage in Rats: Role of Age Dependency

Age-dependent threshold and superthreshold behaviors of ultrasound-induced lung hemorrhage were investigated with one hundred ten 12.6 ± 0.8-d-old rats, one hundred ten 22.9 ± 0.8-d-old rats, and one hundred 57.7 ± 3.9-d-old rats. Exposure conditions were: 2.8 MHz, 10-s exposure duration, 1-kHz pulse repetition frequency and 1.3-μs pulse duration. The in situ (at the pleural surface) peak rarefactional pressure (p_{r(in situ)}) ranged between 1.4 and 10.8 MPa for which there were either 9 or 10 acoustic pressure groups for each of the three rat ages (10 rats/exposure group). For each of the three rat ages there were also shams; there were no lesions in the shams. The p_{r(in situ)} levels were randomized within each age group; rat age was not randomized. Individuals involved in animal handling, exposure and lesion scoring were blinded to the exposure condition. In addition, one hundred fifty-six 72-d-old rats were included from three completed studies (same experimental conditions) to provide a fourth age group for the analysis. Probit regression analysis was used to examine the dependence of the occurrence of lesions on p_{r(in situ)} in the four age groups. Likewise, lesion depth and lesion root surface area were analyzed using Gaussian tobit regression analysis. Although p_{r(in situ)} was a significant variable, no significant age dependence of the p_{r(in situ)} effect was found. Furthermore, age had no significant effect on either the rate of occurrence or the depth of lesions. Given the occurrence of a lesion, a weak age dependence was found for the median surface area of the induced lesion (p-value = 0.037). (E-mail: [email protected]).