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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.
Highlights
The goal of this paper is to evaluate the feasibility of using pulsed US as a therapeutic and non-invasive treatment for cardiovascular disease
Plots for other parameters are provided in the Supplementary Material as follows: Supplemental Figure 1 (Stroke volume), Supplemental Figure 2 (Ejection fraction), Supplemental Figure 3 (Fractional shortening), Supplemental Figure 4 (Respiratory rate) and Supplemental Figure 5 (Arterial pressure)
The Bonferroni test showed a significant effect at 3-min postUS exposures between US and sex
Summary
The goal of this paper is to evaluate the feasibility of using pulsed US as a therapeutic and non-invasive treatment for cardiovascular disease. This study aims to explain the role of this new US therapy in hormonal differences, evaluating pre- and post-menopausal female rats and male rats of different ages. The motivation of this study and long-term goal is to potentially use this alternative therapy as a substitute of pacemakers and eliminate complications caused by the electrodes, broken leads, infections, etc. The authors would like to acknowledge the technical assistance of Rita J. DVM, Emily Hartman, BS, RDMS, and Sandhya Sarwate, MD
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