Cardiopulmonary function in rats with lung hemorrhage induced by pulsed ultrasound exposure.

Abstract

Objective. To assess cardiopulmonary function in rats exposed to pulsed ultrasound using superthreshold exposure conditions known to produce significant lung hemorrhage. Methods. In 1 group of 9 anesthetized SpragueDawley rats, 5 foci of ultrasound-induced hemorrhage were produced in the left lung of each rat. In a second group of 6 rats, 5 foci of ultrasound-induced hemorrhage were produced in the left and right lungs of each rat. Each lesion was induced using superthreshold pulsed ultrasound exposure conditions (3.1-MHz center frequency, 1.7-kHz pulse repetition frequency, 1.3-microsecond pulse duration, 60-second exposure duration, 39-MPa in situ peak compressional pressure, and 17-MPa in situ peak rarefactional pressure). After exposure, the lungs were fixed in formalin and assessed histologically. The total lesion volume was calculated for each lesion in each lung lobe. Measurements of cardiopulmonary function included assessment of pulsatile arterial pressure, heart rate, end-tidal carbon dioxide, respiratory rate, and arterial blood gases (PCO 2 and PO 2 ). Functional data were quantified before (baseline) and 30 minutes after exposure to ultrasound. Results. In the 9 rats that had lesions in only the left lung, the mean (SEM) lesion volume was 97 (13) mm 3 and represented about 3.4% of the total lung volume. In the 6 rats that had lesions in both the left and right lungs, the left, right, and total mean lesion volumes, respectively, were 102 (16), 114 (11), and 216 (18) mm 3 and represented about 3.7%, 4.2%, and 7.9% of the total lung volume. There were no statistically significant differences in cardiopulmonary measurements between baseline values and values obtained after exposure to ultrasound in the 9 rats exposed on the left lung only. The 6 rats exposed bilaterally had statistically significant differences in arterial pressure (134 ± 4 versus 113 ± 9 mm Hg; P = .047) and arterial PO 2 (70 ± 5 versus 58 ± 4 mm Hg; P = .024) between baseline values and values obtained after exposure to ultrasound. Conclusions. The severity of ultrasound-induced lesions produced in 1 lung did not affect measurements of cardiopulmonary function because of the functional respiratory reserve in the unexposed lung. However, when both the left and right lungs had ultrasound-induced lesions, the functional respiratory reserve was decreased to a point at which rats were unable to maintain systemic arterial pressure or resting levels of arterial PO 2 .

Ultrasound-induced lung hemorrhage: Role of acoustic boundary conditions at the pleural surface

“…The first and third exposures were randomized either with the lung deflated or half-deflated. In a previous rat study 38 five adjacent lesions of equal size were created using the same superthreshold exposure conditions. Also, the same 3.1-MHz transducer used herein was used for this previous study.…”

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

“…Concerns for its safety recently were raised and addressed by members of the bioeffects research community [1]. These concerns are the result of a number of ultrasound-induced lung hemorrhage studies in mice, rats, rabbits, monkeys, and pigs [1]- [22] at exposure conditions similar to those used for scanning in humans. Two categories of study have been used to provide insight into extrapolating the laboratory findings to humans.…”

“…One of the categories investigated the physical mechanisms responsible for ultrasound-induced lung hemorrhage including physical variables such as acoustic pressure [2], [5], [6], [8]- [15], [17], [19], [21], [22], center frequency [2], [9], [15], [19], [21], pulse duration [2], pulse repetition frequency [2], [5], [6], [18], exposure duration [3], [5], [6], [12], [14], [18], beam shape and/or size [2], [21], temperature [13] and hydrostatic pressure [17], and biophysical endpoints such as heating [3], [23] and cavitation [3], [11], [17], [24], [25]. The other category has investigated the biological mechanisms responsible for ultrasound-induced lung hemorrhage, including biological variables such as species [9], [15], [18], [19], species age [8], [13], [14], lesion size and/or histological observations [4], [5], …”

Potential Adverse Ultrasound-related Biological Effects

“…Notably, ultrasound-induced lung hemorrhage in animals is not associated with profound hypoxemia, and spontaneous restoration of pulmonary histology and function occurs within a few weeks of the inciting event. 143,144 Indeed, hemolysis, endothelial cell damage, and cardiac myocyte necrosis have been reported during cardiovascular ultrasound applications as microbubble contrast agents decrease the threshold for cavitation. [145][146][147][148][149][150] Ultrasound-induced lung hemorrhage has been widely reported in experimental animals, but perhaps rather surprisingly, humans do not appear to be susceptible to this form of nonthermal injury.…”