Superthreshold behavior of ultrasound-induced lung hemorrhage in adult mice and rats: role of pulse repetition frequency and exposure duration.

Superthreshold behavior for ultrasound-induced lung hemorrhage was investigated in adult mice and rats at an ultrasound center frequency of 2.8 MHz to assess the role of pulse repetition frequency and exposure duration. One hundred fifty, 6-7-week-old female ICR mice and 150 10-11-week-old female Sprague-Dawley rats were each divided into 15 exposure groups (10 animals per group) for a 3 x 5 factorial design (3 exposure durations of 5, 10, and 20 s and 5 pulse repetition frequencies of 25, 50, 100, 250, and 500 Hz). The in situ (at the pleural surface) peak rarefactional pressure of 12.3 MPa and the pulse duration of 1.42 micros were the same for all ultrasonically-exposed animals. In addition, 15 sham exposed mice and 15 sham exposed rats were included into both studies. In each study of 165 animals, the exposure conditions were randomized. The lesion depth and surface area were measured for each animal, as well as the percentage of animals with lesions per group. The characteristics of the lesions produced in mice and rats were similar to those described in studies by our research group and others, suggesting a common pathogenesis for the initiation and propagation of the lesions at the gross and microscopic levels. The proportion of lesions in both species was related statistically to pulse repetition frequency (PRF) and exposure duration (ED), with the exception that PRF in rats was not quite significant; the PRF x ED interaction (number of pulses) for lesion production was not significant for either species. The PRF, but not ED, significantly affected lesion depth in both species; the PRF x ED interaction for depth was not significant for either species. Both PRF and ED significantly affected lesion surface area in mice, while neither affected area in rats; the PRF x ED interaction for surface area was not significant for either species.