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. 2022 Jan;69(1):166-180.
doi: 10.1109/TUFFC.2021.3113867. Epub 2021 Dec 31.

Investigation of the Effects of Cardiovascular Therapeutic Ultrasound Applied in Female and Male Rats' Hearts of Different Ages

Olivia C Coiado, Rahul S Yerrabelli, Anton P Christensen, Marcin Wozniak, William D O'Brien

Investigation of the Effects of Cardiovascular Therapeutic Ultrasound Applied in Female and Male Rats' Hearts of Different Ages

Olivia C Coiado et al. IEEE Trans Ultrason Ferroelectr Freq Control. 2022 Jan.

Abstract

This study investigates the role of age and sex on the cardiovascular effects of 3.5-MHz pulsed ultrasound (US) in a rat model. Ultrasonic bursts of 2.0-MPa peak rarefactional pressure amplitude (equivalent to an in vitro spatial-peak temporal-peak intensity of ~270 W/cm2 and a mechanical index of 1.1) were delivered in five consecutive 10-s intervals, one interval for each pulse repetition frequency (PRF) (6, 5, 4, 5, and 6 Hz; always the same order) for a total exposure duration of 50 consecutive seconds. Sixty F344 rats were split into 12 groups in a 3×2×2 factorial design (three ages, male versus female, and US application versus control). This study is the first study on US-induced cardiac effects that contains data across three age groups of rats (premenopause, fertile, and postmenopause) to mimic the fertile and nonfertile human window. US was applied transthoracically, while heart rate, stroke volume, ejection fraction, temperature, and other physiologic parameters were recorded at baseline and after exposure. Significant decreases in cardiac output compared to respective control groups were observed in multiple experimental groups, spanning both females and males. A negative chronotropic effect was observed in young male (~7%) and female (~16%) rats, in five-month-old male (~9%) and female (~15%) rats, and in old rats where the effect was not statistically significant. Younger groups and, to a lesser extent, lower weight groups generally had more significant effects. The pathophysiology of US-induced cardiovascular effects appears to be multifactorial and not strictly related to hormones, menopause, weight, sex, or age, individually.

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Figures

Fig. 1.
Fig. 1.
B-mode (top) and M-mode (bottom) images of a rat heart (three-month-old female rats) 15 min after US exposure.
Fig. 2.
Fig. 2.
Transducer pressure response at ~2 MPa.
Fig. 3.
Fig. 3.
HR, relative to preultrasound baseline, at the postultrasound times of (a) and (c) 3 and (b) and (d) 15 min. (a) and (b) All 12 subgroups individually (N = 5 ea.), including the six control and six experimental subgroups. (c) and (d) Same data but present the difference between the experimental subgroups and their respective control subgroups.
Fig. 4.
Fig. 4.
CO, relative to preultrasound baseline, at the postultrasound times of (a) and (c) 3 and (b) and (d) 15 min. (a) and (b) All 12 subgroups individually (N = 5 ea.), including the six control and six experimental subgroups. (c) and (d) Same data but present the difference between the experimental subgroups and their respective control subgroups.
Fig. 5.
Fig. 5.
EDV, relative to preultrasound baseline, at the postultrasound times of (a) and (c) 3 and (b) and (d) 15 min. (a) and (b) All 12 subgroups individually (N = 5 ea.), including the six control and six experimental subgroups. (c) and (d) Same data but present the difference between the experimental subgroups and their respective control subgroups.
Fig. 6.
Fig. 6.
ESV, relative to preultrasound baseline, at the postultrasound times of (a) and (c) 3 and (b) and (d) 15 min. (a) and (b) All 12 subgroups individually (N = 5 ea.), including the six control and six experimental subgroups. (c) and (d) Same data but present the difference between the experimental subgroups and their respective control subgroups.
Fig. 7.
Fig. 7.
RT, relative to preultrasound baseline, at the postultrasound times of (a) and (c) 3 and (b) and (d) 15 min. Temperatures converted to kelvin before division. (a) and (b) All 12 subgroups individually (N = 5 ea.), including the six control and six experimental subgroups. (c) and (d) Same data but present the difference between the experimental subgroups and their respective control subgroups.
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