Superthreshold behavior and threshold estimation of ultrasound-induced lung hemorrhage in pigs: role of age dependency

Age-dependent threshold and superthreshold behavior of ultrasound-induced lung hemorrhage were investigated with 116 2.1 +/- 0.3-kg neonate crossbred pigs (4.9 +/- 1.6 days old), 103 10 +/- 1.1-kg crossbred pigs (39 +/-5 days old), and 104 20+/-1.2-kg crossbred pigs (58 +/- 5 days old). Exposure conditions were: 3.1 MHz, 10-s exposure duration, 1-kHz pulse repetition frequency (PRF), and 1.2-micros pulse duration. The in situ (at the pleural surface) peak rarefactional pressure ranged between 2.2 and 10.4 MPa with either eight or nine acoustic pressure groups for each of the three pig ages (12 pigs/exposure group) plus sham exposed pigs. There were no lesions in the shams. Pigs were exposed bilaterally with the order of exposure (left then right lung, or right then left lung) and acoustic pressure both randomized. Pig age was not randomized. Individuals involved in animal handling, exposure, and lesion scoring were blinded to the exposure condition. Logistic regression analysis was used to examine the dependence of the lesion incidence rates on in situ peak rarefactional pressure, left versus right lung exposure, order of exposure (first versus second), and age in three age groups. Likewise, lesion depth and lesion root surface area were analyzed using Gaussian tobit regression analysis. A significant threshold effect on lesion occurrence was observed as a function of age; younger pigs were less susceptible to lung damage given equivalent in situ exposure. Overall, the oldest pigs had a significantly lower threshold (2.87 +/- 0.29 MPa) than middle-aged pigs (5.83 +/- 0.52 MPa). The oldest pigs also had a lower threshold than neonate pigs (3.60 +/- 0.44 MPa). Also, an unexpected result was observed. The ultrasound exposures were bilateral, and the threshold results reported above were based on the lung that was first exposed. After the first lung was exposed, the pig was turned over and the other lung was exposed to the same acoustic pressure. There was a significant decrease (greater than the confidence limits) in occurrence thresholds: 3.60 to 2.68, 5.83 to 2.97, and 2.87 to 1.16 MPa for neonates, middle-aged, and oldest pigs, respectively, in the second lung exposed. Thus, a subtle effect in lung physiology resulted in a major effect on lesion thresholds.