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-mus 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).